ArticlePDF Available

Health Effects of Probiotics on the Skin

Critical Reviews In Food Science and Nutrition

December 2013
55(9)

DOI:10.1080/10408398.2012.680078

Source
PubMed

Authors:

Mohammad Rahmati

Amirkabir University of Technology

Reza Karimi

University of Guilan

Amir Mohammad Mortazavian

Shahid Beheshti University of Medical Sciences

Abstract Skin is the largest organ of the body and is constantly exposed to physical, chemical, bacterial and fungal challenges. It is well known that probiotics are helpful for specific disorders and different clinical studies have indicated that probiotics have special effects in cutaneous apparatus directly or indirectly which can be considerable from versatile aspects. Probiotic bacteriotherapy can have great potentials in preventing and treating the skin diseases including eczema, atopic dermatitis, acne, allergic inflammation or in skin hypersensitivity, UV-induced skin damage, wound protection and cosmetic products. The current article comprehensively reviews the different health effects of probiotics on the skin.

Health consequences of probiotics to the skin.

…

The main mechanisms involved in health benefits of probiotics to the skin.

…

Figures - uploaded by Amir Mohammad Mortazavian

Content may be subject to copyright.

Content uploaded by Amir Mohammad Mortazavian

Content may be subject to copyright.

This article was downloaded by: [University of Maine - Orono]

On: 25 April 2015, At: 03:57

Publisher: Taylor & Francis

Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,

37-41 Mortimer Street, London W1T 3JH, UK

Click for updates

Critical Reviews in Food Science and Nutrition

Publication details, including instructions for authors and subscription information:

http://www.tandfonline.com/loi/bfsn20

Health Effects of Probiotics on the Skin

M. Rahmati Roudsaria, R. Karimib, S. Sohrabvandic & A. M. Mortazavianb

a Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

b Students' Research Committee, National Nutrition and Food Technology Research Institute,

Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical

Sciences, Tehran, Iran

c Department of Food Science and Technology, Faculty of Nutrition Sciences, Food Science

and Technology/National Nutrition and Food Technology Research Institute, Shahid Beheshti

University of Medical Sciences, P.O. Box 19395-4741, Tehran, Iran

Accepted author version posted online: 23 Dec 2013.

To cite this article: M. Rahmati Roudsari, R. Karimi, S. Sohrabvandi & A. M. Mortazavian (2015) Health Effects of Probiotics on

the Skin, Critical Reviews in Food Science and Nutrition, 55:9, 1219-1240, DOI: 10.1080/10408398.2012.680078

To link to this article: http://dx.doi.org/10.1080/10408398.2012.680078

PLEASE SCROLL DOWN FOR ARTICLE

Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained

in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no

representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the

Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and

are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and

should be independently verified with primary sources of information. Taylor and Francis shall not be liable for

any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever

or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of

the Content.

This article may be used for research, teaching, and private study purposes. Any substantial or systematic

reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any

form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://

www.tandfonline.com/page/terms-and-conditions

Critical Reviews in Food Science and Nutrition, 55:1219–1240 (2015)

 Taylor and Francis Group, LLC

ISSN: 1040-8398 / 1549-7852 online

DOI: 10.1080/10408398.2012.680078

Health Effects of Probiotics

on the Skin

M. RAHMATI ROUDSARI,1R. KARIMI,2S. SOHRABVANDI,3

andA.M.MORTAZAVIAN

1Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2Students’ Research Committee, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and

Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3Department of Food Science and Technology, Faculty of Nutrition Sciences, Food Science and Technology/National Nutrition

and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, P.O. Box 19395-4741, Tehran, Iran

Skin is the largest organ of the body and is constantly exposed to physical, chemical, bacterial, and fungal challenges. It

is well known that probiotics are helpful for speciﬁc disorders and different clinical studies have indicated that probiotics

have special effects in cutaneous apparatus directly or indirectly that can be considerable from versatile aspects. Probiotic

bacteriotherapy can have great potential in preventing and treating the skin diseases including eczema, atopic dermatitis,

acne, and allergic inﬂammation or in skin hypersensitivity, UV-induced skin damage, wound protection, and as a cosmetic

product. The current paper comprehensively reviews the different health effects of probiotics on the skin.

Keywords Allergy, atopic dermatitis, eczema, probiotic, skin

INTRODUCTION

Skin is the body’s interface with the environment. The skin

forms a critical structural boundary and a perceptual interface

for the Human and it is an immunogenic organ that works as

the ﬁrst defense and biologic sensor against external allergens.

Recent research efforts to understand the control of skin barrier

functions point to a close association among physical, immuno-

logical, and cell biological characteristics of the skin and its

microﬂora (Elias and Choi, 2005). Enhancing skin barrier may

be of importance particularly in certain inﬂammatory diseases

where barrier function is impaired such as atopic dermatitis, dry

skin, or in aging. Barrier function experiences a variety of tests

on a daily basis including environmental, chemical, or physi-

cal factors (UV radiation, pollution, hot and cold temperatures,

air-conditioning, low humidity level, etc.), psychological stress

and/or dietary deﬁciencies (Gu´

eniche et al., 2010b).

Probiotics are “live microorganisms, which, when adminis-

tered in adequate amounts, confer a health beneﬁt to the host”

(Anon., 2006). It has been speculated that the skin status could

Address correspondence to A. M. Mortazavian, Department of Food Sci-

ence and Technology, Faculty of Nutrition Sciences, Food Science and Tech-

nology/National Nutrition and Food Technology Research Institute, Shahid Be-

heshti University of Medical Sciences, P.O. Box 19395-4741, Tehran, Iran.

E-mail: mortazvn@sbmu.ac.ir

beneﬁt from reinforced gut homeostasis (Salminen et al., 2005).

Diet variations determine individual characteristics of intesti-

nal microﬂora, according to age, feeding, lifestyle, interactions

among numerous constituents of the same ﬂora, and pathologic

conditions. Probiotic formulations are becoming increasingly

available for healthy skin care, prevention and treatment of skin

diseases, and antiaging beneﬁts, thus representing an emerg-

ing area for skin health (Cinque et al., 2011). The advantages

of probiotic-treatment (probiotic-prevention and/or probiotic-

therapy) are that this method is efﬁcient to the patients and also

it has no side effect on them. Therefore, probiotic-therapy for

the skin is potentally comparable to the ordinary methods of

treatments.

Modern lifestyle negatively inﬂuences the intestinal ecosys-

tem, and there may be cumulative degradation of the intesti-

nal microﬂora. Linear changes in environmental conditions and

lifestyle may lead to nonlinear changes in the gut ﬂora possibly

to an increasing susceptibility to skin diseases (Schmidt, 2004).

A number of clinical studies suggest that probiotic strategies in-

duce systemic effects that extend beyond the gut and may even

affect selected functions of the skin (Ouwehand et al., 2002;

Guenche et al., 2006).

Many experimental studies have shown that probiotics ex-

ert speciﬁc inﬂuences in the intestinal on epithelial cells and

immune cells with antiallergic potential (Caramia et al., 2008).

1219

Downloaded by [University of Maine - Orono] at 03:58 25 April 2015

1220 M. R. ROUDSARI ET AL.

Also, an emerging approach in dermatology to help preventing

and treating skin conditions, including the external signs of ag-

ing, acne, rosacea, yeast and bacterial infections, psoriasis, and

dermatitis, is represented by topical probiotics, as shown by the

growing marketplace for topical probiotic formulations avail-

able for skin care and antiaging beneﬁts (Cinque et al., 2011).

Totally, probiotics exert their health effects to the skin directly

through cutaneous formulations or indirectly through dietary

supplementary formulations and intestinal microﬂora improve-

ment.

There are some review articles in which some parts are re-

lated to the relationships between probiotics and the skin in

pediatrics (Caramia et al., 2008) and some parts are related

to speciﬁcs disorders such as atopic dermatitis (Flohr et al.,

2005; Halvarsson and Lod´

en, 2007) or brieﬂy summarized crit-

ical overview about the use of pre- and/or probiotica in clinical

dermatology (Krutmann, 2009). Also, there are some reviews

about the effects of probiotics on allergic diseases (Kirjavainen

et al., 1999; Ogden and Bielory, 2005; Rautava et al., 2005;

Boyle and Tang, 2006; Michail, 2009), probiotics in aging skin

(Cinque et al., 2010), dermal applications of probiotics (Cinque

et al., 2011), and gut–brain–skin axis (Bowe and Logan, 2011).

However, in none of them, the effects of different probiotics on

skin health along with the related mechanisms are comprehen-

sively and extensively discussed. This paper fulﬁlls mentioned

apects.

MICROORGANISMS OF THE SKIN AND THE

POSITION OF PROBIOTICS

The skin microﬂora plays a signiﬁcant role in competitive

exclusion of pathogens that are aggressive and provoke infec-

tion in the skin and in the processing of skin proteins, free fatty

acids, and sebum (Cinque et al., 2011). Scientiﬁc research in

the composition and function of the skin’s microﬂora is recently

experiencing a revival, and has become one of the most inter-

esting and developing areas in cutaneous biology (Cogen et al.,

2008).

The skin has a normal microbiota (Tannock, 1995). This

normal microbiota of the skin is likely to be involved in com-

petitive exclusion of pathogens, a function that could possibly

be enhanced with the use of probiotics (Ouwehand et al., 2003).

Certain probiotics can contribute to modulate cutaneous mi-

croﬂora, lipid barrier, and skin immune system, leading to the

preservation of the skin homeostasis (Cinque et al., 2011). Cu-

taneous immune surveillance is required to protect the organism

from infections but also to detect and remove transformed cells,

which eventually may give rise to skin carcinomas (Euvrard

et al., 2003; Woods et al., 2005).

A limited number of gram-positive species have evolved to

take advantage of the harsh environmental conditions that are

being offered by the skin (Leyden et al., 1987). Resident micro-

bial species including Proprionibacteria (P. acnes,P. avidum,

and P. granulosum), coagulase-negative Staphylococci (S. epi-

dermidis), Micrococci, Corynebacteria, and Acinetobacter, and

transient species including S. aureus,E. coli,Pseudomonas

aeroguinosa, and Bacillus species are present on the skin (Krut-

mann, 2009). Recent studies using 16SrRNA gene survey strate-

gies showed that the human skin microbiota is far more complex

(Grice et al., 2008). It has been noted that S. epidermidis is the

dominant aerobic bacteria resident in skin (Grice et al., 2008)

and the presence of this species could affect the skin barrier

function and/or the development of innate immune responses

in human skin. The resident microﬂora may be regarded as

“beneﬁcial” to the “normal, healthy” host, but may become

dangerous to the host with disturbed skin integrity (Krutmann,

2009). There is some evidence that the skin microﬂora activates

the adaptive (not non-adaptive) immune system. In this regard,

microorganisms on the skin have been shown to be coated with

immunoglobulins that are most likely derived from eccrine gland

secretions (Metze et al., 1991).

The number of microbial species existing on human skin is

determined by a variety of physical (including the number and

size of follicles and glands, gland function, the ﬂow of secre-

tions, the integrity of barrier function, skin pH, and osmotic

potential) and biochemical factors (including soluble micronu-

trients derived from sebum—such as lipids and aminoacids-

and sweat—such as vitamins and lactate and amino acids—as

well as those produced as a consequence of the metabolic ac-

tivity of microorganisms on the skin; e.g., lantibiotics produced

by Staphylococcus spp., methantiol, bacteriocins, organic acids,

and lytic enzymes) (Krutmann, 2009).

Cutaneous pH can control bacterial populations on skin

surface affecting resident microﬂora and can regulate epider-

mal permeability barrier homeostasis and stratum corneum

integrity (Feingold, 2007). Elevation in stratum corneum pH

is associated with several cutaneous disorders, such as acute

eczema, atopic dermatitis, and seborrheic dermatitis. In these

diseases the increased pH could adversely affect cutaneous

functions exacerbating these conditions further with more se-

vere clinical manifestations (Cinque et al., 2010). Use of probi-

otics with fermentative metabolism that are able to produce

lactic acid and obtain energy from the fermentation of lac-

tose, glucose, and other sugars to lactate via homofermentative

metabolism (Farmer, 2005; Chiba, 2007) could be an interesting

approach.

In atopic skin reduced level of sphingosine is suggested to

be responsible for the changed pattern of microorganisms on

the skin surface. Reduction of sphingosine has been found

linked to the increased numbers of bacteria including S. au-

reus present in the upper stratum corneum (Arikawa et al.,

2002). The presence of the lipophilic yeasts Malassezi spp.

(formerly known as Pityrosporum ovale and orbiculare) has

been suggested to be responsible for an exacerbation of the

eczema of the head, neck, and shoulders named “head-and-

neck dermatitis” in young adults (Halvarsson and Lod´

en,

2007).

Downloaded by [University of Maine - Orono] at 03:58 25 April 2015

HEALTH EFFECTS OF PROBIOTICS ON THE SKIN 1221

HEALTH BENEFITS OF PROBIOTICS TO THE SKIN

Probiotic microorganisms can improve health of skin by oral

consumption (in vivo usage) or by local application on it (in

vitro usage). Oral consumption has been the subject of many

studies in recent years. Probiotics might exhibit preventive or

therapeutic effects on the skin.

The health consequences of probiotics to the skin are shown

in Fig. 1. Fig. 2 indicates the main mechanisms involved in

health beneﬁts of probiotics to the skin.

It has been revealed that not only diseased, but also healthy

skin may proﬁt from the oral ingestion of probiotic bacteria

(Holma et al., 2011). Research about the skin health beneﬁts

of probiotics indicated that oral consumption might reduce skin

sensitivity and support the skin’s immune function. In one clin-

ical trial, oral consumption of a Lactobacillus johnsonii supple-

ment for six weeks appeared to accelerate the recovery of the

skin’s immune system compared to the placebo (Gueniche et al.,

2009), while another study indicated a combination of Lac-

tobacillus paracasei and Biﬁdobacterium lactis decreased the

skin’s neurosensitivity in women with reactive skin (Gueniche

et al., 2007). Puch et al. (2008) in a double-blind, randomized

clinical study have indicated that a 24-week skin nutrition inter-

vention with a fermented dairy product containing L. casei,L.

bulgaris, and Streptococcus thermophilus in female volunteers

with dry and sensitive, but healthy skin reduced transepidermal

water loss and thus improved stratum corneum barrier function

(Puch et al., 2008).

It has been found that oral consumption of probiotic bacte-

ria may represent a novel approach to protect the skin immune

system against ultraviolet radiation (UVR). Some effects have

been reported in hairless mice and it has been indicated that nu-

tritional supplementation with L. johnsonii provided protection

of the skin immune system against ultraviolet (UV) B radiation-

induced immunosuppressive effects (Gueniche et al., 2006). It

has been hypothesized a unifying model, gut–brain–skin axis,

which suggesting that modulation of the microbiome by de-

ployment of probiotics can exert beneﬁcial inﬂuences on skin

inﬂammation, skin homeostasis, hair growth, and peripheral tis-

sue responses to stress (Arck et al., 2010).

Biﬁdobacteria can produce a further riboﬂavin (vitamin B2).

Deﬁciencies in riboﬂavin, a co-enzyme involved in numerous

redox reactions, can lead to skin disorders (Lakshini, 1998). Two

biﬁdobacteria strains (B.infantis CCRC 14633 and B.longum

B6) have been reported to increase the levels of riboﬂavin during

a 48-h fermentation in soymilk (Hou et al., 2000). Physiological

and measurable changes in vivo show at an ingested quantity of

at least 108–109cfu per day, so that immune modulating effects

are inducible with a daily ingestion of 100 g probiotic yogurt

with 106cfu per gram (Karimi et al., 2011, 2012; Korbekandi

et al., 2011). It has been reported that L. rhamnosus GG, in

high concentrations (lyophilic capsule form), exhibited positive

effects on skin especially to its some diseases such as atopic

eczema, and this cannot be efﬁciently achieved by intake of

available supplemented foods (Bunselmeyer and Buddendick,

2010). The main positive effects of probiotics on skin health are

discussed below.

Effects of Probiotics on Eczema and Atopic Dermatitis

Atopic dermatitis is the most common chronic skin condition

in infants and children, with a prevalence of 10–20% (Laughter

et al., 2000; Schultz-Larsen, 2002; Kliegman et al., 2007). It

has been deﬁned as “a skin condition characterized by intense

dryness of the skin, pruritus, and chronic erythematous lesions

with a relapsing course” (del Giudice jr et al., 2002). Atopic

dermatitis is a chronic relapsing inﬂammatory skin disease that

usually starts during the ﬁrst years of life. In patients with the

disease, the quality of skin is severely affected, and this is closely

linked to a reduced quality of life. The course of atopic dermati-

tis is characterized by sub-acute and chronic stages, as well as

the acute ﬂare stage. The sub-acute stage includes mild scaling

and mild licheniﬁcation (thickened skin caused by scratching)

of the skin and the chronic stage includes prominent scaling

with distinct licheniﬁcation (Carroll et al., 2005). An increas-

ing prevalence of this disease has been observed during recent

years (Halvarsson and Lod´

en, 2007). Atopic dermatitis has been

linked to food hypersensitivity, especially milk and egg proteins

(Sicherer and Sampson, 1999).

Epidemiological studies have shown lower incidence of

atopic skin and hypersensitivity complaints among children with

stable gastrointestinal populations of lactobacilli and biﬁdobac-

teria compared with those who had a paucity of gut probiotic

microorganisms (Cross, 2002). On the other hand, impairment

of the intestinal mucosal barrier appears to be involved in the

pathogenesis of atopic dermatitis (Rosenfeldt et al., 2004). The

“hygiene hypothesis” is a current popular theory to describe

why we are experiencing a surge in atopic disease prevalence

(Noverr and Huffnagle, 2005). According to this theory, our

environments are now too clean and we are not exposed to as

many antigens (bacterial, fungal, viral) as previous generations.

With a reduction in infectious exposure, certain individuals over

time may produce altered gastrointestinal, immunologically ac-

tive microorganisms, leading to a TH2 immune shift (Duramad

et al., 2006). Numerous researches also have supported a corre-

lation among early life antibiotic exposure and atopy in children

(Johnson et al., 2005; Kummeling et al., 2007).

Clinical investigation of probiotics’ therapeutic potential in

atopic dermatitis reﬂects a growing interest in therapeutic target-

ing of intestinal colonization and TH1/TH2 immunologic matu-

ration (Lee et al., 2008a). Atopic diseases involve TH2 responses

to allergens (Romagnani, 1996). Probiotics can potentially mod-

ulate the toll-like receptors and the proteoglycan recognition

proteins of enterocytes, leading to activation of dendritic cells

andaT

H1 response. The resulting stimulation of TH1 cytokines

can suppress TH2 responses (Winkler et al., 2007). Although

it has long been appreciated that some are at higher risk for

atopic disorders based on family history, it should be recog-

nized how complicated the nature–nurture equation might be

Downloaded by [University of Maine - Orono] at 03:58 25 April 2015

1222 M. R. ROUDSARI ET AL.

Health consequences of

probiotics to the skin

Preventing and

clinical

improvement of

eczema and

atopic dermatitis

disorders

Reducing

transepidermal

water loss and

improving

stratum corneum

barrier function

Produce a

further

riboflavin

(vitamin B2)

Having

adjuvant role

in acne

therapy

Wound

protection

Exhibiting

anti-allergic

and anti-

inflammatory

effects

Beneficial

influences on skin

inflammation, skin

homeostasis, hair

growth, and

peripheral tissue

responses to stress

Protect the skin

immune system

against

ultraviolet

radiation

Protection

against

ultraviolet-

induced skin

damage

Maintaining

skin freshness

and

youthfulness

(anti-ageing

property)

Preventing

overgrowth

of harmful

microflora of

the skin

Figure 1 Health consequences of probiotics to the skin.

(Rosen and Breuner, 2007). Even single nucleotide polymor-

phisms (SNPs, or very small DNA shifts) may not only account

for the presence or absence of atopy in a given person but

may also affect the severity of disorder, the likelihood of other

atopic conditions developing, and the success of various ther-

apies (Negoro et al., 2006). A baby who has a given genomic

predisposition, under certain environmental conditions, mani-

fests immune dysregulation, resulting in an imbalance between

TH1-dominant and TH2-dominant responses (Kidd, 2003). TH2

dominance leads to immune dysregulation marked by a prolif-

eration of inﬂammatory cellular mediators (e.g., cytokines, in-

terleukins, leukotrienes). Inﬂammation involves excess mucous

production and other clinically observable phenomena that are

called allergies.

Pediatric studies suggest that probiotic use in children

with atopic conditions such as atopic dermatitis results in en-

hancement of IFN-production and decrease d IgE and antigen-

induced TN F-, IL-5, and IL-10 secretion (Prescott et al., 2005;

Taylor et al., 2006; Flinterman et al., 2007). The use of probiotic

microorganisms in the primary prevention of atopic disease is

based on the ability to reverse increased intestinal permeability,

a characteristic of children with atopic eczema and food allergy

(Caramia et al., 2008). Speciﬁc species and strains of indige-

nous gastrointestinal microﬂora have been indicated to have

Health benefits of

probiotics to the skin

Oral consumption

(in the intestine)

Competition with harmful

skin microflora

Reduction of pH

Secretion of useful

metabolites

Inhibition of allergen-

induced tumors

(changes in systemic

immune responses)

Immunomodulation of the

skin in numerous ways

(changes in systemic

immune responses)

Local

application on

the skin

Barrier to harmful foreign

environmental factors that are in

contact with the skin (protective shield)

Inhibition of

harmful intestinal

microflora

Act as antioxidant agents

(protection against

oxidative stresses)

Figure 2 The main mechanisms involved in health beneﬁts of probiotics to the skin.

Downloaded by [University of Maine - Orono] at 03:58 25 April 2015

HEALTH EFFECTS OF PROBIOTICS ON THE SKIN 1223

important inﬂuences on the physiology and immunology of the

host. L. rhamnosus GG and B. lactis Bb-12 are an effective ad-

junct to extensively hydrolyzed formula in treating infants with

mild atopic dermatitis, and the combination of L. rhamnosus

19070-2 and L. reuteri DSM 122460 is effective in patients with

moderate to severe atopic dermatitis (Caramia et al., 2008).

It has been suggested that topical application of Vitreoscilla

ﬁliformis exerts beneﬁcial effects in patients with seborrheic

dermatitis and atopic eczema (Gueniche et al., 2006, 2007).

Majamaa and Isolauri (1997) studied the ﬁrst double-blind

placebo-controlled intervention regarding cutaneous patholo-

gies to improve the atopic manifestations, dermatitis/eczema

with probiotics (Majamaa and Isolauri, 1997). They studied the

immunologic and clinical effects of cow’s milk elimination in

children with or without L. rhamnosus GG in hydrolyzed for-

mula that administered to mothers of 10 breast-feed children

with atopic eczema and cow’s milk allergy. In their study, a

signiﬁcant improvement in atopic dermatitis was observed after

one month of intervention only in those receiving L. rhamnosus

GG. The concentrations of fecal α1-antitrypsin and tumor necro-

sis factor α(determined as markers of intestinal inﬂammation

before and after dietary intervention) signiﬁcantly decreased in

the group receiving L. rhamnosus GG. They concluded that

probiotic bacteria may be effective probably by improving en-

dogenous barrier mechanisms in patients with atopic dermatitis

and food allergy, and minimizing intestinal inﬂammation may

act as a useful tool in the treatment of food allergy (Majamaa

and Isolauri, 1997).

In the research performed by Isolauri et al. (2000), the effects

of probiotics in atopic eczema in a randomized double-blind

study were monitored. A total of 27 infants with atopic der-

matitis during exclusive breast-feeding were divided into three

groups: probiotic-supplemented, B. lactis Bb-12 or L. rhamno-

sus GG, and extensively hydrolyzed whey formulas or the same

formula without probiotics. A signiﬁcant reduction in SCO-

RAD score (severity scoring of atopic dermatitis) (Anon., 1993;

Kunz et al., 1997; Charman and Williams, 2000; Pucci et al.,

2005) was seen after two months in the probiotic-supplemented

groups. Also, a decrease in the serum concentration of inﬂam-

matory markers (such as the marker of T-cell activation) and

urinary eosinophil protein X (a marker of eosinophilic inﬂam-

matory activity) was also seen, suggesting that probiotics may

counteract inﬂammatory responses beyond the intestinal tract

(Isolauri et al., 2000).

In the study accomplished by Rautava et al. (2002),

L. rhamnosus GG was administered (2 ×1010 cfu) to 62

mother–infant pairs during the four weeks before birth and

during breastfeeding for three months. In their double-blinded,

placebo-controlled study, the immunoprotective potential of

breast milk was increased with L. rhamnosus GG, as assessed

by the amount of anti-inﬂammatory transforming growth

factor-β2 in milk of mothers receiving probiotics versus

placebo. Their study revealed that the risk of developing atopic

eczema throughout the ﬁrst two years of life in babes whose

mothers received probiotics was signiﬁcantly decreased. Also,

it was argued that infants most likely to beneﬁt from probiotics

are those with elevated cord blood IgE concentration (Rautava

et al., 2002). However, this has limited applications because this

particular study involved exclusively breast-feeding mothers

who ingested the probiotics and presumably passed it to their

infants through breast milk. Also, in this regard, Kalliom¨

aki

et al. (2003) administered L. rhamnosus GG (1010 cfu) in a

double-blind, randomized, placebo-controlled trial during four

weeks before birth and throughout breast-feeding for three

months to mothers who had at least 1 ﬁrst-degree relative with

atopic eczema and to their infants after birth for six months. In

their study, chronic recurring atopic eczema, which is the major

sign of atopic disease in the ﬁrst years of life, was the primary

end point. The frequency of atopic eczema in the probiotic

group was half that of the placebo group. They concluded that

L. rhamnosus GG was effective in prevention of early atopic

disease in children at high risk, and the preventive effect was

still effective after four years (Kalliom¨

aki et al., 2001, 2003).

Hattori et al. (2003) studied 15 children with atopic der-

matitis with Biﬁdobacterium-deﬁcient microﬂora. Eight chil-

dren were given oral administration of lyophilized B. breves M-

16V strain. Signiﬁcant improvement of allergic and cutaneous

symptoms was seen in the biﬁdobacteria-administered group

(Hattori et al., 2003). Kirjavainen et al. (2003) investigated 35

infants (mean age of 5.5 months) with atopic eczema in a ran-

domized, double-blind research. The infants were assigned to

receive either extensively hydrolyzed whey formula as placebo

group or the same formula supplemented with viable L. rham-

nosus GG or heat-inactivated LGG. Scores in SCORAD in the

viable L. rhamnosus GG group tended to be more than within

the placebo group, suggesting the possible beneﬁts of probiotics

as a primary intervention in eczema. While live probiotic ad-

ministration resulted in statistically signiﬁcant improvement of

scores, the use of heat-inactivated L. rhamnosus GG was associ-

ated with adverse gastrointestinal symptoms (Kirjavainen et al.,

2003). Another study by Kirjavainen et al. (2002) suggested that

B. lactis Bb-12 modiﬁes gut microﬂora to alleviate early onset

atopic eczema (Kirjavainen et al., 2002).

In the study of Rosenfeldt et al. (2003), the use of probiotics

as an adjuvant to topical steroids (hydrocortisone or hydrocorti-

sone butyrate) in the treatment of established atopic dermatitis

in a double-blind, placebo-controlled crossover study was in-

vestigated. The subjects aged 1–13 years with severe chronic

eczema took either a combination of 2 Lactobacillus strains

(L. rhamnosus GG 19070-2 and L. reuteri DSM 122460) or

placebo for six weeks. In their study 56% of probiotic-treated

patients experienced subjective symptom improvement com-

pared with 15% of placebo-group patients and eczema extent

decreased. Also, serum eosinophilic cationic protein values used

to monitor disease activity in atopic dermatitis decreased with

probiotic therapy. Probiotic therapy was accompanied by only

moderate changes in production of the cytokines IL-4, IFN-γ,

and IL-10. The modest inﬂuence of the probiotics on the im-

provement of atopic dermatitis could be attributed to the older

age of the subjects and the severity of the eczema (Rosenfeldt

Downloaded by [University of Maine - Orono] at 03:58 25 April 2015

1224 M. R. ROUDSARI ET AL.

et al., 2003). Also, Rosenfeldt et al. (2004) in a double-blinded,

placebo-controlled, cross-over study administered L. rhamno-

sus 19070-2 and L. reuteri DSM 12246 to 41 children with

moderate and severe atopic dermatitis for six weeks. In their

study, gastrointestinal symptoms were registered before and

during treatment. Small intestinal permeability was also mea-

sured by the lactulose-mannitol test because patients with atopic

dermatitis appear to have an increased intestinal permeability

(Pike et al., 1986; Caffarelli et al., 1993). It was found that there

is a positive association between the lactulose to mannitol ratio

and the severity of the eczema. They concluded that probiotic

supplementation may stabilize the intestinal barrier function

and decrease gastrointestinal symptoms in children with atopic

dermatitis (Rosenfeldt et al., 2004).

In the study of Pohjavuori et al. (2004), L. rhamnosus GG

and a mixture of four bacterial species or placebo were admin-

istered for four weeks to infants with suspected IgE-associated

dermatitis in a randomized, double-blind study with elimina-

tion diet and skin treatment. Between the infants who received

L. rhamnosus GG, the level of secreted interferon γincreased

in those with IgE-associated dermatitis in comparison to the

placebo group. Deﬁciency in interferon γappears to be related

to production rises with the addition of L. rhamnosus GG. In-

terferon γrises in infants with IgE-associated dermatitis. This

may reﬂect the beneﬁcial immunomodulatory signals that probi-

otics can provide (Pohjavuori et al., 2004). Weston et al. (2005)

studied 56 children with moderate or severe atopic dermati-

tis in a randomized, double-blind, placebo-controlled trial. The

children received L. fermentum VRI-033 PCC or an equivalent

volume of placebo for eight weeks. Reduction in severity and

extent of atopic dermatitis was signiﬁcant in the probiotic group

at the end of the study. Children with moderate or severe disease

receiving probiotics had a SCORAD index that was more than

baseline at the end of the study (Weston et al., 2005). In the

study of Prescott et al. (2005), it was indicated that the admin-

istration of L. fermentum was correlated with an increase, from

peripheral blood mononuclear cells, in T-helper type 1 cytokine

interferon γresponses and S. aureus enterotoxin B at the end

of the eight-week supplementation period. The increase in in-

terferon γresponses to S. aureus enterotoxin B was directly

proportional to the decrease in the severity of atopic dermatitis

(Prescott et al., 2005).

Viljanen et al. (2005) treated a total of 230 infants aged

1.4–11.9 months with atopic eczema/dermatitis syndrome in

a randomized, double-blinded study a mixture of four probi-

otic strains (L. rhamnosus GG ATCC 53103, L. rhamnosus

LC705, B. breve Bbi99, and P. freudenreichii ssp. shermanii

JS) or placebo for four weeks. After four-week treatment, IgA

levels tended to be higher in probiotic groups than in the placebo

group, and α1- antitrypsin decreased in the probiotic group but

not in other treated groups. They did not report any date on cuta-

neous ﬁndings after treatment. They reported that the combining

LGG with other probiotic strains suppressed the effect seen with

LGG alone (Viljanen et al., 2005). Smits et al. (2005) studied

monocyte-derived dendritic cells cultured in vitro with L. reuteri

and L. casei. They explain the beneﬁcial effect of noted probi-

otics in the treatment of several inﬂammatory diseases including

atopic dermatitis through the production of cytokines without in-

creasing the production of immunomediator IL-10 (Smits et al.,

2005). Penders et al. (2006) revealed that C. diﬁcile colonization

at one month of age was associated with an increased likelihood

of eczema, recurrent wheezing, and atopic dermatitis. In their

study, E. coli colonization was associated with eczema rather

than recurrent wheezing or atopic dermatitis. Also, no associa-

tion with biﬁdobacteria colonization, B. fragilis or lactobacilli

colonization was observed (Penders et al., 2006). Sistek et al.

(2006) showed efﬁcacy of the probiotic L. rhamnosus and B.

lactis on atopic dermatitis in food-sensitized children (Sistek

et al., 2006).

Gr¨

uber et al. (2007) investigated the therapeutic beneﬁt of L.

rhamnosus GG (LGG) in infants with atopic dermatitis. In their

study infants 3–12 months of age with mild-to-moderate atopic

dermatitis were randomized to receive LGG or placebo as a

food supplement for 12 weeks. Fifty-four infants received LGG

and 48 infants received placebo. Symptoms improved overtime

after 4, 8, and 12 weeks, without any group being statistically

different (Gr¨

uber et al., 2007). Michail et al. (2008) in a meta-

analysis including ten randomized, controlled trials, found a

signiﬁcant overall beneﬁt after the use of probiotics, resulting

in a reduction of the dermatitis scores (SCORAD) compared to

placebo. In their study, L. rhamnosus GG appeared to be more

effective than other probiotic preparations and children with

more severe disease were more likely to beneﬁt from the use

of probiotics (Michail et al., 2008). Other studies have shown

less atopic eczema with supplementation with Lactobacillus

rhamnosus GG (LGG) (Kalliom¨

aki et al., 2007). L. rhamnosus

GG in vitro has been shown to inhibit antigen-induced IgE

production in murine lymphocytes (Shida et al., 1998).

Wickens et al. (2008) studied the role of probiotics in pre-

vention of development of eczema and atopy in early life at two

years in a double-blind, randomized placebo-controlled trial. In

their study, pregnant women were randomized to take L. rham-

nosus HN001, B. animalis subsp. lactis strain HN019 or placebo

daily from 35 weeks gestation until six months if breastfeeding,

and their infants were randomized to receive the same treatment

from birth to two years. They found that supplementation with

L. rhamnosus, but not B. animalis ssp. lactis, substantially re-

duced the cumulative prevalence of eczema, but not atopy, by

two years (Wickens et al., 2008). Similar results were found in

other studies (Osborn and Sinn, 2007; Lee et al., 2008a). In the

study of Bard et al. (2008), 19 subjects with atopic dermati-

tis aged six months to eight years were randomized to receive

10–20 ×109cfu of LGG or placebo daily during a 9- to 12-

week intervention phase. It was concluded from their research

that LGG may lead to a signiﬁcant decrease in IgE sensitized

patients and although the ﬁnal average SCORADs for both the

LGG and placebo groups were comparable, patients receiving

LGG had a signiﬁcant greater decrease in severity of symptoms

over the ﬁrst three weeks of treatment as compared to the control

group (Bard et al., 2008).

Downloaded by [University of Maine - Orono] at 03:58 25 April 2015

HEALTH EFFECTS OF PROBIOTICS ON THE SKIN 1225

Kim et al. (2009) indicated that supplementation of pro-

biotics at four to eight weeks before delivery and continuing

until six months after delivery can prevent the development of

eczema in infants at high risk. They also showed that the preva-

lence of eczema at one year in the probiotic group was signiﬁ-

cantly lower than in the placebo group (Kim et al., 2009). A re-

cent prospective, double-blind, randomized, placebo-controlled

clinical trial performed on 50 subjects aged 3–47 months with

moderate/severe AD showed that 12 monthsof L. reuteri supple-

mentation may be beneﬁcial in the longterm control of eczema

(Gromert and Axelsson, 2009). In the study of Niers et al. (2009)

a mixture of probiotic bacteria including B. biﬁdum,B. lactis,

and Lactococcus lactis was prenatally administered to mothers

of high-risk children and to their offspring for the ﬁrst 12 months

of life. In their study parental-reported eczema during the ﬁrst 3

months of life was signiﬁcantly lower in the intervention group

and there was signiﬁcant decrease in IL-5 production compared

with placebo group. Also they showed that the preventive effect

of the combination of particular probiotic bacteria on the inci-

dence of eczema sustained during the ﬁrst 2 years of life (Niers

et al., 2009).

Kuitunen et al. (2009) in a double-blinded, placebo-

controlled study randomized 1,223 mothers with infants at high

risk for allergy to receive a probiotic mixture (L. rhamnosus

LC705 DSM 7061, LGG 53103, B. breve Bb99 DSM 13692

and P. freudenreichii ssp. shermanii JS DSM 7076) or placebo

during the last month of pregnancy and their infants to receive it

from birth until age six months. Infants also received a prebiotic

galactooligosaccharide or placebo. At ﬁve years the cumulative

incidence of eczema was evaluated. No signiﬁcant difference

appeared between the probiotic and placebo groups in frequen-

cies of eczema or atopic eczema. However, signiﬁcantly fewer

IgE-associated eczema occurred in cesarean-delivered children

receiving probiotics. In vaginally delivered children no signiﬁ-

cant differences appeared between treatment groups (Kuitunen

et al., 2009). Farid et al. (2011) studied the clinical and immuno-

logic effects of mixture of seven strains of probiotic bacteria

(L. casei, L. rhamnosus, S. thermophilus, B. breve, L. aci-

dophilus, B. infantis, L. bulgaricus) and Fructooligosaccharide

in 40 infants and children aged three months to six years with

atopic dermatitis. They concluded that the mixture of seven

strains of probiotics and Fructooligosaccharide can clinically

improve the severity of atopic dermatitis in young children

(Farid et al., 2011).

Despite some disparities between studies, the weight of evi-

dences suggests a protective role for at least some Lactobacillus

species in the pathogenesis of eczema, but there is little evidence

overall that this is mediated through effects on allergic sensiti-

zation (Wickens et al., 2008). In the study of Abrahamsson et al.

(2007) the mothers received the probiotic daily from gestational

week 36 until delivery and their babies then continued with the

same product from birth until 1-year of age and were followed

up for second year. In their research using L. reuteri ATCC

55730 no overall effect on the cumulative incidence of eczema

was found despite a reduction in IgE-associated eczema (Abra-

hamsson et al., 2007). Also, some studies have found no effect

of L. acidophilus LAVRI-A1 (Taylor et al., 2007) or L. rham-

nosus GG (Kopp et al., 2008) on atopic dermatitis and even it

has been reported that L. acidophilus supplementation actually

increase the risk of atopic sensitization (Taylor et al., 2007). It

is interesting that the results of Kopp et al. (2008) were in sharp

contrast with the study of Kalliomaki et al. (2001) although an

identical probiotic strain was used (LGG) in an also otherwise

comparable study design. There were two main differences be-

tween Taylor’s study (2007) and the other researchers. The type

of probiotic product was different as well as the timing of the in-

troduction of the probiotic. Taylor et al. (2007) administered the

probiotic supplement postnatally, while other studies adminis-

tered probiotics before and after birth. Prenatal supplementation

may prove to be crucial for the preventive beneﬁt of probiotics

in this disorder.

Brouwer et al. (2006) and Folster-Holst et al. (2006) showed

no effect of L. rhamnosus GG in infants with atopic dermatitis

regardless of their IgE sensitization status (Brouwer et al., 2006;

Folster-Holst et al., 2006). In the research of Osborn and Sinn

(2007), a meta-analysis described ﬁve studies enrolling 1,477

infants. They concluded that there was no current evidence to

support the administration of probiotics to prevent eczema and

recommended further studies to determine reproducibility (Os-

born and Sinn, 2007). In the study of Lee et al. (2008), in a

meta-analysis no therapeutic difference was shown among chil-

dren receiving probiotics (Lee et al., 2008a). Their evidence

is more convincing for probiotics’ efﬁcacy in prevention than

treatment of pediatric atopic dermatitis. There have been some

reports of adverse reactions when pediatric patients with cow’s

milk protein allergy ingested probiotics (Lee et al., 2007). It is

necessary to mention that prescribing such probiotics especially

in the sensitized children need more caution.

Although there is still a potential role for probiotics in pre-

venting childhood atopic dermatitis and other allergic diseases,

there are many unanswered questions, including species/strain

selection, dosing and timing of probiotic administration and the

population or populations most likely to beneﬁt (Ji, 2009; Kopp

and Salfeld, 2009; von Hertzen et al., 2009; Ly et al., 2011).

Understanding how probiotics act to prevent eczema requires

further investigation and more research is needed to determine

the ideal composition of different types of pre- and probiotics for

atopy prevention and treatment. The main studies of probiotic

effects on atopic dermatitis are summarized in Table 1.

Effects of Probiotics on Acne

In some investigations, the impacts of internal application of

probiotic supplements on acne has been discussed (Bowe and

Logan, 2011). There are some studies that made no positive cor-

relation among fermented dairy products and acne (Adebamowo

et al., 2005, 2006, 2008). On the other hand, some studies have

stated that there is an association between acne and growth hor-

mones of milk (Melnik and Schmitz, 2009). Acne is driven with

Downloaded by [University of Maine - Orono] at 03:58 25 April 2015

Tab l e 1 Studies of probiotic effects on atopic dermatitis

Probiotic microorganisms Patients (N, age) Administered dose Period of study Conclusions and remarks References

L. rhamnosus GG ATCC

53103

925 infants 5 ×109cfu 6 mo No effect of probiotics vs placebo on cumulative

incidence of allergic diseases, but tended to reduce

IgE-associated (atopic) diseases, probiotics reduced

eczema

(Kukkonen et al., 2007)

L. rhamnosus LC705

DSM7061

5×109cfu

B. breve Bb99 DSM

13692

2×108cfu

P. freudenreichii ssp.

shermanii JS DSM

7076

2×109cfu daily

L. acidophilus LAVRI-A1 178 infants 3 ×109cfu daily 6 mo No reduction in AD at 6 mo vs placebo groups,

Paradoxical increase in sensitization to allergens in

probiotics supplemented infants

(Taylor et al., 2007)

L. reuteri ATCC 55730 188 infants 108cfu daily mothers from gestational age 36 wk

to delivery, then infants

supplemented for 1 y, then

followedfor1y

Cumulative incidence of eczema similar in probiotics

and placebo groups, Probiotics group had less

IgE-associated eczema during second year

(Abrahamsson et al.,

2007)

L. rhamnosus GG

ATCC53013

31 infants aged 2.5–15.7

months

5×108cfu 4 wk After 4 wk of intervention, signiﬁcant SCORAD score

reduction in probiotic group, decrease of

α1-antitrypsin and tumor necrosis factor α

(Majamaa and Isolauri,

1997)

L. rhamnosus GG ATCC

53103

119 infants aged 1.4–11.5 m

(mean age 6.5 m)

— 4 wk Increase of IFN-γin those with IgE-associated

dermatitis

(Pohjavuori et al., 2004)

L. rhamnosus GG

L. rhamnosus LC705

B. breve Bbi99

P. freudenreichii ssp.

Shermanii JS

L. rhamnosus 19070-2 43 patients aged 1–13 years 1010 cfu twice daily 18 weeks No overall signiﬁcant change in total SCORAD after

treatment, 56% of patients who took probiotics

experienced improvement of eczema, compared with

15% of patients who took placebo, probiotic effect

seen only in IgE-sensitized group

(Rosenfeldt et al., 2003)

L. reuteri DSM 12246

L. rhamnosus GG 35 infants, mean age 5.5

months

3×108cfu 0.4 to 45.3 wk SCORAD scores decreased 19 to 5 in viable LGG

group, Treatment with heat inactivated LGG

associated with adverse gastrointestinal symptoms

and diarrhea

(Kirjavainen et al., 2003)

LGG ATCC53103 230 Infants aged 1.4–11.9

months (mean age 6.4

months)

5×109cfu 4 weeks IgA levels tended to be higher in probiotic groups,

α1-antitrypsin decreased in the probiotic group, IL-6

and IL-10 increased in LGG and MIX groups more so

than in placebo for IgE independent AD, Probiotic

effect seen only in IgE-sensitized group

(Viljanen et al., 2005a)

1226

Downloaded by [University of Maine - Orono] at 03:58 25 April 2015

L. rhamnosus LC705 5 ×109cfu

B. breve Bbi99 2 ×108cfu

P. freudenreichi ssp

shermani JS

2×109cfu

L. fermentum VRI-033

PCC

53 children aged 6–18

months

1×109cfu 8 week Older children (mean age, 11.5 mo) with more severe

dermatitis are more likely to show improvement of

lesions statistically with probiotics, More children in

probiotics group signiﬁcantly had score improvement

than those given placebo

(Weston et al., 2005)

L. rhamnosus GG 19 children aged 6 months

to 8 years

10–20 ×109cfu 9–12 week Signiﬁcant greater decrease in severity of symptoms in

probiotic group

(Bard et al., 2008)

L. rhamnosus GG ATCC

53013

53 children aged 1–55

months

5×109— No improvement over placebo (Folster-Holst et al.,

2006)

L. rhamnosus Lcr35 39 children aged 2–12 y 1.2 ×109cfu

3 times daily

3 months Improvement in prebiotic and synbiotic groups (Passeron et al., 2006)

L. rhamnosus GG ATCC

53013

102 children aged 3–12

months

5×10912 weeks No signiﬁcant improvement in AD among probioticand

placebo groups

(Gr¨

uber et al., 2007)

L. rhamnosus GG ATCC

53103

925 infants 5 ×109cfu/capsule 2 years Decrease of prevalence of AE at age of 2 years (eczema

without IgE sensitization)

(Kukkonen et al., 2007)

L. rhamnosus LC705

DSM7061

5×109cfu/capsule

B. breve Bb99 DSM

13692

2×108cfu/capsule

P. freudenreichii spp.

Shermanii JS DSM

7076

2×109cfu/capsule

L. rhamnosus GG 94 — 2 years No difference in prevalence of AE at age of 2 years (Kopp et al., 2008)

L. rhamnosus HN001 446 infants 6 ×109cfu 2 years Decrease of prevalence of eczema in L. rhamnosus

group

(Wickens et al., 2008)

B. animalis subsp. lactis

HN019

9×109cfu daily

L. rhamnosus LC705

DSM 7061

891 infants 5 ×109cfu 6 mo No change in AE prevalence at the age of 5 years,

decrease of prevalence of AE at 5 years of life in

cesarean-delivered children

(Kuitunen et al., 2009)

LGG 53103 5 ×109cfu

B. breve Bb99 DSM

13692

2×108cfu

P. freudenreichii ssp.

shermanii JS DSM

7076

2×109cfu twice

daily

L. casei 40 infants and children

aged3moto6y

1×109cfu twice

daily

8 wk Improvement of atopic dermatitis with the mixture of

the seven strains of probiotics and

Fructooligosaccharide

(Farid et al., 2011)

L. rhamnosus

S. thermophilus

B. breve

(Continued on next page)

1227

Downloaded by [University of Maine - Orono] at 03:58 25 April 2015

Tab l e 1 Studies of probiotic effects on atopic dermatitis (Continued)

Probiotic microorganisms Patients (N, age) Administered dose Period of study Conclusions and remarks References

L. acidophilus

B. infantis

L. bulgaricus (mixture)

L. fermentum PCC 56 infants aged 6–18 mo — 8 wk Increase of IFN-γand TNF-α, decrease of IL-13 and

decrease in the severity of AD in probiotic group

(Prescott et al., 2005)

B. breve M-16V 15 children 5–15 ×109cfu 1 mo Improvement of allergic and cutaneous symptoms (Hattori et al., 2003)

L. rhamnosus GG 15 infants 3 ×108cfu/g — Signiﬁcant changes in plasma lipid PUFA composition

were detected, both groups inﬂuenced the proportions

of n-3 PUFA in neutral lipids; both reduced the

proportion of α-linolenic acid

(Kankaanpaa et al.,

2002)

B. lactis Bb-12 1 ×109cfu/g

B. lactis Bb-12 13 infants 8 ×1010 cfu/kg

body weight

— SCORAD drop in 50% of placebo group and 100% of

probiotics group

(Kirjavainen et al., 2002)

L. rhamnosus and B. lactis

(Combined)

59 Children aged 1–10 y 2 ×1010 cfu daily 12 wk Signiﬁcant AD improvement only observed in food

sensitized children

(Sistek et al., 2006)

L. rhamnosus 50 Infants 5 ×109cfu/100 mL

formula

12 wk No signiﬁcant clinical effect of probiotics on AD

severity was detected, Differences in SCORAD at

randomization and subsequent decrease in SCORAD

during treatment were not signiﬁcant

(Brouwer et al., 2006)

LGG aged 1.1–5.2 mo 3 ×108cfu/100 mL

formula

L. rhamnosus 19070-2 41 Children aged 1–13 y

(mean age 4 y)

1010 cfu 18 wk Small intestinal permeability (Lactulose-Mannitol test) (Rosenfeldt et al., 2004)

L. reuteri DSM12246

1228

Downloaded by [University of Maine - Orono] at 03:58 25 April 2015

HEALTH EFFECTS OF PROBIOTICS ON THE SKIN 1229

insulin-like growth factor I (IGF-I) and IGF-I can be absorbed

across colonic tissue (Quadros et al., 1994). It should be noted

that probiotic bacteria utilize IGF-I throughout the fermentation

when added to milk, with a resultant four-fold lower level of

IGF-I in fermented versus skim milk (Kang et al., 2006).

In a study, 40 patients added: an oral supplement of 250 mg

freeze-dried L. acidophilus and B. biﬁdum as an adjuvant to

standard care in half of the group. In addition to better clini-

cal outcomes among the patients supplemented with probiotics,

the researchers reported better tolerance and compliance with

antibiotics (Marchetti et al., 1987). Another research supported

the beneﬁt of probiotics added to standard care, with a reported

acceleration in time to signiﬁcant clinical improvement in those

who had been administered probiotics (Volkova et al., 2001).

The study of Kim et al. (2010) showed that the consumption of

aLactobacillus-fermented dairy beverage improved clinical as-

pects of acne over 12 weeks. They found that the probiotic drink

consumption led to signiﬁcant reductions in total lesion count in

association with a marked reduction in sebum production. Al-

though in their study the added lactoferrin (an anti-inﬂammatory

milk protein) to the probiotic drink provide higher efﬁcacy in

the decrease of inﬂammatory lesions, the beneﬁts of the probi-

otic drink lonely lend more support to the notion that probiotics

have an adjuvant role to play in acne therapy (Kim et al., 2010).

Various probiotic lactic acid bacteria can provide in vitro

antimicrobial activity against P. acnes (Kang et al., 2009;

Al-Ghazzewi and Tester, 2010). Kang et al. (2009) found that

topical application of an Enterococcus faecalis probiotic lo-

tion for eight weeks reduced inﬂammatory lesions by over 50%

versus placebo (Kang et al., 2009). S. salivarius (a prominent

member of the oral microbiota of healthy humans) has been

indicated to secrete a bacteriocin-like inhibitory substance ca-

pable of inhibiting P. acnes (Bowe et al., 2006). In addition to the

antimicrobial activity, S. salivarius inhibit a number of inﬂam-

matory pathways, thus acting as immune modulators (Cosseau

et al., 2008).

Acne vulgaris is multifactorial condition and is character-

ized by hypercolonization with P. acnes, inﬂammation, and im-

mune responses. Propionibacteria have been shown to have adju-

vant and antitumor activities (Eady and Ingham, 1994) and also

same species are of pathogenic relevance in acne and folliculitis

(Leyden et al., 1998). The synbiotic ability of probiotic bacteria

and Konjac glucomannan hydrolysates to inhibit the growth of

P. acnes in an in vivo study has been recently reported suggest-

ing that the development of a new alternative involving probiotic

therapy for reducing acne episodes in vivo could be encouraging

(Al-Ghazzewi and Tester, 2009).

The local burden of lipid peroxidation in acne is high, such

that it appears to place a great demand upon blood-derived an-

tioxidants (Bowe and Logan, 2010). Some recent studies have

shown that orally consumed pre- and probiotics can reduce sys-

temic markers of inﬂammation and oxidative stress (Schiffrin

et al., 2007; Mikelsaar and Zilmer, 2009). Then the ability of oral

probiotics to limit systemic oxidative stress may be an impor-

tant therapeutic pathway (Fu et al., 2010). Oral administration

of probiotics regulates the release of inﬂammatory cytokines

within the skin (Hacini-Rachinel et al., 2009), and a speciﬁc

reduction in interleukin-1α(Cazzola et al., 2010), would be of

potential beneﬁt in acne (Bowe and Logan, 2011).

Researchers have shown that S. thermophilus can increase

ceramide production when applied to the skin for seven days

as a cream (Di Marzio et al., 1999, 2003, 2008) and some

of the ceramide sphingolipids, most notably phytosphingosine,

provide both antimicrobial activity against P. acnes and direct

anti-inﬂammatory activity (Pavicic et al., 2007). Sphingolipids

have been reported to be low in acne (Yamamoto et al., 1995),

and the seasonal loss of ceramides can be a driving force be-

hind much more dermatological ofﬁce visits for acne throughout

winter months (Hancox et al., 2004).

Substance P may be a primary mediator of stress-induced

ampliﬁcation of inﬂammation and sebum production in acne

(Lee et al., 2008b). It has been reported that strains of B.

longum and L. paracasei can attenuate skin inﬂammation me-

diated by substance P (Gu´

eniche et al., 2010b, Gueniche et al.,

2010a). In this regard, Gueniche et al. (2010a) showed that

L. paracasei CNCM-I 2116 was able to abrogate vasodilation,

edema, mast cell degranulation, and TNF-alpha release which

induced by substance P, compared to control. They showed that

medium conditioned with L. paracasei (inexvivoskinorgan

culture) induced a signiﬁcantly faster barrier function recovery

after sodium lauryl sulphate disruption, compared to control

(Gueniche et al., 2010a). Also, Gueniche et al. (2010b) per-

formed an in vitro and a clinical trial using B. longum extract

proved that these nonreplicating bacteria forms applied to the

skin were able to improve sensitive skin in various parameters

associated with inﬂammation, such as decrease in vasodilation,

edema, mast cell degranulation, and TNF-alpha release. Their

ﬁndings suggested that B. longum bacterial extract may prevent

negative environmental effects (cold in winter, air dryness) and

its application contributes to reinforce skin homeostasis and

to improve skin resistance to external abuse (Gu´

eniche et al.,

2010b).

Anti-Allergic and Anti-Inﬂammatory Effects of Probiotics

on the Skin

The role of probiotics in prevention of allergic disease is

still not clearly established. It has been shown that probiotics

exert speciﬁc antiallergic effects on epithelial cells and immune

cells. The allergen penetration through the skin can lead to a

systemic sensitization involving the intestinal mucosa. Also, it

has been reported that inﬂammation plays an important role in

photoageing of human skin in vivo (Pillai et al., 2005).

Intervention strategies have been elaborated to balance the

intestinal microecology with oral administration of probiotics

(Miraglia and De Luca, 2004; Ogden and Bielory, 2005). The

composition of the intestinal microﬂora is the main element in

allergic diseases, and species of probiotics could play a role in

the development of healthy immunity response, participating

Downloaded by [University of Maine - Orono] at 03:58 25 April 2015

1230 M. R. ROUDSARI ET AL.

in enteric microecology, preventing, and potentially treating al-

lergic diseases (Macpherson and Harris, 2004; Noverr and Huff-

nagle, 2004; Zutavern et al., 2006). It should be mentioned that

not all probiotics have the identical immunological characteris-

tics. The anti-inﬂammatory properties of probiotics have been

shown of cell homogenates of L. rhamnosus GG, L. rhamnosus

LC705, B. animalis Bb-12, L. acidophilus NCFB-L61748, L.

bulgaricus ATCC 11842, S. thermophilus T101, and P. freuden-

reichii Shermanii strain JS (Kankaanpaa et al., 1998). Simi-

lar ﬁndings have been reported in other studies (Kankaanpaa

et al., 2002). It has been reported that L. reuteri has displayed a

slightly different proﬁle than other probiotic bacteria and seems

to possess more pronounced anti-inﬂammatory properties, as

demonstrated in animal and human in vitro studies (Ma et al.,

2004; Peˇ

na et al., 2005; Smits et al., 2005; Zeuthen et al., 2005).

Probiotic bacteria may mediate antiallergenic effects by stim-

ulating production of TH1-cytokines (Miettinen et al., 1998;

Hessle et al., 1999), transforming growth factor-β(Isolaurietal.,

2000; Paganelli et al., 2002) and and gut IgA (Fukushima et al.,

1999; Kirjavainen et al., 1999). Allergic responses are thought

to arise if there is absence of microbial exposure while the im-

mune system is still developing. Exposure to microbial ﬂora

early in life allows for a change in the TH1/TH2 balance, favor-

ing a TH1 cell response (Ogden and Bielory, 2005; Ouwehand,

2007).

Dietary supplementation using particular probiotic strains

has been found to increase interferon activity in the blood of hu-

man, and children born to families who consume traditional Lac-

tobacillus-rich fermented foods experience fewer allergies than

those from families who consume more sterile foods (Caramia

et al., 2008).

It has been conﬁrmed that children who develop allergies

present low levels of biﬁdobacteria, gram-positive aerobic or-

ganisms, and enterococci, but more elevated levels of clostridia

and S. aureus in their enteric microﬂora. Increased fecal levels

of i-caproic acid that are indicators of high level of Clostridium

difﬁcile, suggest that the enteric microﬂora could be changed

in allergic children. Many factors exert the alteration of gas-

trointestinal ﬂora equilibrium such as genetic factors, diet, and

infection frequency, antibiotic therapies, passive smoke, pollu-

tion, vaccinations, psychologic stresses, reduction of immuno-

logic activity, and development of allergic diseases and some in-

ﬂammatory diseases (Alm, 2002; Halken, 2004). For example,

antibiotic therapy leads to changes in intestinal, bacterial, and

fungal components and also to overgrowth of Candida albicans,

which can secrete potent prostaglandin-like immune response

modulators and subsequently promote the development of aller-

gic events in distal mucosal sites such as the skin (Noverr et al.,

2005). It should be noted that not all probiotic microorganisms

have the same immunologic properties and speciﬁc probiotic mi-

croorganisms of the developing intestinal microﬂora that most

inﬂuence skin health need to be deﬁned because speciﬁc devia-

tions in intestinal microﬂora may exert predisposition to allergic

disease (Caramia et al., 2008). Totally, allergic responses may

also be affected by dose and viability of the probiotic and these

factors in turn potentially modiﬁed by the host environment

(Wickens et al., 2008).

Atopic infants have been shown to have overactive phago-

cytes (Isolauri et al., 1997), which may contribute to the al-

lergic inﬂammation. Probiotics appear to modulate phagocy-

tosis differently in healthy and allergic subjects (Pelto et al.,

1998). For example, L. rhamnosus GG has been demonstrated

to be capable of alleviating the overactive phagocytic process

induced by cow’s milk challenge in milk-hypersensitive sub-

jects (Kirjavainen et al., 1999). Also in other studies its has

been demonstrated that LGG administration, along with milk,

was associated with immunostimulatory effects in healthy hosts,

whereas in milk hypersensitive infants, it was associated with

anti-inﬂammatory effects (Pelto et al., 1998).

Halper et al. (2003) investigated the anti-inﬂammatory po-

tential of probiotics, the in vitro and in vivo effects of super-

natants from L. acidophilus 4356 and 43121 on tissue repair

and angiogenesis. They found that Lactobacillus supernatant

promoted proinﬂammatory processes including chemoattrac-

tion of polymorphonuclear cells, macrophages, angiogenesis

and stimulation of production of TNFαand other cytokines

including interleukins and interferons (Halper et al., 2003). It

has been indicated that allergic sensitization/IgE-associated sta-

tus and greater pediatric atopic dermatitis severity correlated

with stronger therapeutic response to probiotics supplementa-

tion (Lee et al., 2008a). However, in a meta-analytic study, it has

been noted that there was no signiﬁcant change to conﬁrm that

IgE sensitization was indeed a factor in determining the efﬁcacy

of probiotics (Michail et al., 2008).

Effects of Probiotics on Ultraviolet-Induced Skin Damage

UVR is responsible for both acute and long-term effects

(Moyal and Fourtanier, 2004). UVR also induces cutaneous

inﬂammation with development of erythema, edema, and hyper-

proliferation of the epidermis giving rise to ﬂaking or scaling

(Soter, 1990). Approximately 50% of UVR-induced damage

has been estimated to result from production of reactive oxygen

species (Bernstein et al., 2004).

Some researchers pertained to the use of probiotics for

the preparation of a carrier for balancing the skin’s immune

function under stress conditions, such as a exposure to UVR,

speciﬁcally for enhancing the skin’s immune activity and

reducing the tendency to develop allergic reactions under such

conditions (Baur et al., 2003). Bouilly-Gauthier et al. (2010)

used L. johnsonii La1 and nutritional doses of carotenoids in

139 healthy women over 18 years of age for 10 weeks to protect

skin immune system homeostasis following UV exposure.

They concluded that nutritional supplementation containing L.

johnsonii and doses of carotenoids reduced early UV-induced

skin damage caused by simulated or natural sun exposure

(Bouilly-Gauthier et al., 2010). In their study, sun protection

factor measurement was based on the determination of the

minimal erythemal dose. Their ﬁndings indicated that probiotic

Downloaded by [University of Maine - Orono] at 03:58 25 April 2015

HEALTH EFFECTS OF PROBIOTICS ON THE SKIN 1231

dietary supplement intake resulted in a 19% increase in the

UV dose required to produce erythema. This increase could be

perceived as small regarding the sun protection factor provided

by sunscreens, but the tested nutritional supplement exhibited

this increase of minimal erythemal dose without the absorbing

or reﬂecting properties of sunscreens (Bouilly-Gauthier et al.,

2010). It should be noted that lower skin erythema could result

in less inﬁltration by neutrophils which release proteolytic

enzymes such as elastase and metalloproteases that could play a

role in skin photoageing (Rijken et al., 2005). Bouilly-Gauthier

et al. (2010) also observed that cumulative exposures to

suberythemal doses of UV daylight resulted in a signiﬁcant

decrease in Langerhans cell density. It was shown that probiotic

dietary supplement intake signiﬁcantly prevented this decrease,

suggesting a positive effect of dietary supplement in sustaining

the cutaneous immune system following UVR exposure. Also

they found that probiotic dietary supplementation signiﬁcantly

reduced the induced increase in CD45+dermal inﬂammatory

cells, suggesting a beneﬁcial effect of probiotic dietary

supplement intake on UV-induced inﬂammation and probably

on photoageing (Bouilly-Gauthier et al., 2010).

Gueniche et al. (2006) studied the oral supplementation of

probiotic L. johnsonii La1 in hairless Skh:hr1 mice for 10 days

to protect against UV-induced suppression of contact hyper-

sensitivity, decrease of Langerhans cell density and increase

of interleukin-10 serum levels. They found that in the absence

of UV exposure, L. johnsonii La1 had no detectable effect on

the immune system of the skin, thus acting only to re-establish

skin homeostasis. They also demonstrated that ingested probi-

otic bacteria can maintain cutaneous immune capacity after UV

exposure. Their results suggested that La1 contributes mainly

to reinforce skin homeostasis rather than boosting the cuta-

neous immune defense per se (Gueniche et al., 2006). It has

been revealed that L. johnsonii La-1 accelerate the recovery

of Langerhans cell functionality after UVR exposure in humans

(Peguet-Navarro et al., 2008). In another study it has been shown

that the probiotic strain L. casei DN-114001 is able to decrease

skin inﬂammation in a dinitroﬂuorobenzene contact hypersen-

sitivity model (Chapat et al., 2004) showing an effect in the

absence of any UV challenge.

Effects of Probiotics on Wound Protection

Many authors have demonstrated that certain bacterial pro-

biotic extracts have anti-adhesion and anti-microbial properties

when applied to cutaneous and mucous surfaces (Rodriguez

et al., 2005). Probiotic microorganisms use different mecha-

nisms, such as by lowering pH, to preserve skin health and

to inhibit the growth of pathogens (Arck et al., 2010). The

acidic skin environment is indeed very important as it dis-

courages bacterial colonization and provides a moisture barrier

through absorption or moisture by aminoacids, salts, and other

substances in the acid mantle (Lambers et al., 2006; Mauro,

2006).

The potential use of probiotic microorganisms capable of

producing antimicrobial toxins (bacteriocins, bacteriocin-like

substances, organic acids, and H2O2) (Bernet-Camard et al.,

1997; Coconnier et al., 1998) has received increasing attention

to successfully prevent pathogen adhesion and outcompete un-

desired species (Gillor et al., 2008). Teodorescu (1999) used

a mixture of three L. acidophilus strains, LD-11, LR-13, and

LV-17 in a eubiotic product for the maintenance and treatment

of tegument. The three noted strains could ferment rafﬁnose,

trehalose, and dextrin, respectively. Also these strains were ca-

pable to maintain the skin pH at physiological values, to destroy

the pathogenic microﬂora and to be resistant in cosmetic com-

position (Teodorescu, 1999).

Oh et al. (2006) reported the efﬁcacy of the bacteriocin from

Lactococcus sp. HY 449 in controlling skin-inﬂammation and

acnes by clinical skin irritation test. They demonstrated that this

bacteriocin was able to inhibit the growth of skin inﬂamma-

tory bacteria such as S. epidermidis,S. aureus,S. pyogenes, and

P. acnes due to bacteriolytic action on the cell wall and cell

membranes especially in P. acnes (Oh et al., 2006). It has been

claimed that extracts of Lactobacillus could stimulate the pro-

duction of beta-defensins in skin cells, which can be beneﬁcial in

the reduction or prevention of growth of microbial populations

on the skin, in a dose-dependent manner (Sullivan et al., 2009).

Effective amounts of Lactobacillus extracts can be applied to

an open cut or wound on the skin that may have been in contact

with dirt or undesirable microbes; or on a chronic basis, applied

to clean skin to maintain a healthy level of skin ﬂora. Also,

L. plantarum extract are shown to reduce the incidence of both

inﬂamed and noninﬂamed acne lesions. The extracts had fur-

ther been proposed as a preservative in cosmetic of pharmaceu-

tical products, in particular the L. plantarum, which possesses

a broad spectrum of activity against both gram-positive and

gram-negative bacteria (Cinque et al., 2011).

It has been suggested that L. plantarum and/or its products are

potential therapeutic agents in the local treatment of P. aerug-

inosa burn infections. Regarding this matter, it has been also

shown that the in vitro treatment with L. plantarum is able

to inhibit the production of the P. aeruginosa quorum-sensing

signal molecules, acyl-homoserine-lactones, and two virulence

factors controlled by these signal molecules elastase and bioﬁlm

(Vald´

ez et al., 2005). Peral et al. (2009a) studied the effect of

topical L. plantarum treatment on infected and non-infected

second-degree burn patients and on infected third-degree burn

patients. They found that the ability of L. plantarum to prevent

infection, to decrease in the bacterial load, to promote granu-

lation tissue, and to heal wounds was comparable to the silver

sulphadiazine cream one (Peral et al., 2009a). Also the study of

Peral et al. (2009b) showed the efﬁcacy of L. plantarum bac-

teriotherapy on the chronic infected leg ulcers of diabetic and

nondiabetic patients (Peral et al., 2009b).

Hansen and Jespersen (2010) invented a tissue dressing

comprising bacteria (including L. sporogenes,L. acidophilus,

L. plantarum,L. casei,L. brevis,L. delbruckii, and L. lactis)

having the property of producing lactic acid by fermentation

Downloaded by [University of Maine - Orono] at 03:58 25 April 2015

1232 M. R. ROUDSARI ET AL.

of the sugars, to use in healing wounds or in accelerating the

wound healing (Hansen and Jespersen, 2010). These species

of lactic acid bacteria were capable of lowering the pH in an

open wound environment, securing an intraspecies competitive

exclusion thus preventing growth of undesirable bacterial

species, exerting an immunomodulatory effect by inducing

“wound healing-promoting substances” and producing certain

bacteriocins such as toxins that can sustain a wound-healing

process. Jones et al. (2010) showed that the NO-producing pro-

biotic patch device containing lyophilized alginate-immobilized

L. fermentum, glucose, and nitrite salts can produce sufﬁcient

levels of gaseous NO over a therapeutically relevant duration,

to kill common bacterial and fungal pathogens existed in the

wounds of humans (Jones et al., 2010).

Ouwehand et al. (2003) studied the in vitro potential use of

probiotic Propionibacteria (P. acidipropionici 4900, P. freuden-

reichii ssp. Shermanii 4902, P. freudenreichii ssp. Freudenreichii

20271, P. thoenii 20277 and P. jensenii 20278) and L. rhamnosus

for the skin and their production of anti-microbial substances

against selected skin pathogens (Malassezia furfur 6170, M. fur-

fur L1510, M. furfur L1796, C. albicans 1665, C. albicans 3454,

S. aureus 346 and S. aureus 20231) as well as their adhesion to

human keratin (the main protein of the skin). In their study, P.

freudenreichii ssp. freudenreichii 20271 and L. rhamnosus 5.5a

exhibited signiﬁcantly higher adhesion to keratin than the other

tested strains. Also they found that C. albicans strains were

found to be sensitive and S. aureus 346 exhibited higher adhe-

sion to keratin, signiﬁcantly better than all other tested strains,

both the potential probiotics and the target strains. According

to their results, although P. freudenreichii ssp. Freudenreichii

20271 and L. rhamnosus 5.5a adhered in relatively high lev-

els to the immobilized keratin, they were not able to prevent

the adhesion of the tested target organisms (Ouwehand et al.,

2003). In some studies, to avoid the risk of infection, it has been

advised not to apply probiotics to damaged skin (Ouwehand

et al., 2003). Some selection criteria for probiotics in the skin

have been advised to apply. For example, adhesion, inhibition of

pathogen adhesion and production of antimicrobial substances

is important for an application on the skin (Ouwehand et al.,

2003).

MECHANISMS OF INTESTINAL EFFECTS

OF PROBIOTICS ON THE SKIN

Studies suggest that probiotics potentially act favorably in

the host through several different mechanisms. The knowledge

of these mechanisms provided a useful molecular model to fo-

cus on innovative therapeutic applications. The mechanism of

probiotic bacteria in atopic dermatitis patients is not exactly un-

derstood, but it has been reported that inﬂammatory responses

have been detected after treatment with probiotic bacteria, indi-

cating that an innate immune response pattern may underlie the

therapeutic effect (Viljanen et al., 2005).

A number of immunologic pathways have been indicated

to be inﬂuenced by probiotic microorganisms, involving differ-

ent mechanisms. Probiotic effects may be local, and potentially

include reduction of permeability and systemic penetration of

antigens, alteration of local inﬂammation or tolerance induc-

tion, anti-inﬂammatory effects mediated by Toll-like receptors,

activation of tolerogenic dendritic cells, TH1 skewing of re-

sponses; alteration of T-regulatory function, and increased local

IgA production (Wickens et al., 2008). Systemic effects with

increased monocytes and effects on T cells, B cells, and stem

cells have also been suggested (Prescott and Bjorksten, 2007).

Some strains of lactobacilli and biﬁdobacteria have been shown

to modulate IL-10 production, possible enhancing regulatory

or tolerance-inducing mechanisms (Niers et al., 2005). It has

been reported that certain probiotic bacteria are able to stim-

ulate the production of TH1 cytokines (Miettinen et al., 1998;

Hessle et al., 1999), transforming growth factor beta (Paganelli

et al., 2002), and gut IgA (Fukushima et al., 1999; Kirjavainen

et al., 2003). Also, in other studies it has been reported that the

transient protection offered by probiotics against IgE-associated

allergic diseases is based on stimulation of Toll-like receptors,

which produce mediators such as IL-6 and these further induce

IgA differentiation from naive B cells (Sato et al., 2003).

It has been indicated that L. rhamnosus weakly stimulates

dendritic cell maturation (Veckman et al., 2004). Its peptido-

glycan cell wall binds to Toll-like receptor 2 (Yoshimura et al.,

1999) and induces the expression of proinﬂammatory and anti-

inﬂammatory cytokines (Netea et al., 2004). Probiotic strains

that stimulate the expression of regulatory cytokines have effec-

tively prevented or alleviated eczema (Majamaa and Isolauri,

1997; Kalliom¨

aki et al., 2001; Ling et al., 2004). In a research,

combining LGG with three other probiotics suppressed the ben-

eﬁcial effects seen with LGG alone, perhaps due to an interfer-

ence of immunostimulating effects between the strains (Viljanen

et al., 2005).

Allergic diseases are associated with an imbalance in the

TH1/TH2 cytokine, activation of TH2 cells and with stimula-

tion of IgE and IgA synthesis, leading to allergic reactions

(Kruisselbrink et al., 2001; Winkler et al., 2007). Probiotics in-

hibit the TH2 response while stimulating the production of TH1

and TH1 cytokines, such as interferon γ(Isolauri et al., 2001;

Ghadimi et al., 2008). Also, some studies on the effect of lacto-

bacilli on immune cells in animal or in vitro models have shown

promotion of TH1-like responses with IFN-g, IL-12, and IL-18

activation, which inhibites development of a TH2-like deviation

in infants (Vaarala, 2003). Probiotics have a strain-dependent

capability to endow T cells with regulatory properties (Tregs).

Such induction of Tregs by probiotics may involve APCs (mono-

cytes, dendritic cells), or a direct action on T cells, and may take

place in the intestine, where these cells encounter commensal

bacteria (Feleszko et al., 2007; Adkinson et al., 2009; Fink,

2010). It has been found that the use of probiotics is associated

with an inhibition of allergen-induced tumor necrosis factor

α, IgE, and several allergy-induced cytokine (Prescott et al.,

2005; Flinterman et al., 2007).

Downloaded by [University of Maine - Orono] at 03:58 25 April 2015

HEALTH EFFECTS OF PROBIOTICS ON THE SKIN 1233

It has been demonstrated that in atopic dermatitis and

allergic contact dermatitis, skin-activated T cells stimulated

Fas-induced keratinocyte apoptosis. In particular, diseased

skin-inﬁltrating T cells produce IFN-γthat increasing Fas

receptor number on keratinocyte membrane renders them

susceptible to apoptosis by Fas ligand expressed on or released

by T cell surface (Trautmann et al., 2001). The discovery

of TH17, a new lineage of THcells that produce IL-17 and

effects of microbiota on the balance between these cells and T

cells with regulatory properties development is a new era for

research (Mucid and Salek-Ardekani, 2009).

It can be concluded that the mechanism of the effects of

probiotic gut ﬂora on skin is represented by changes in sys-

temic immune responses. In particular, modulation of speciﬁc

T-cell subsets such as stimulation of TH1 cells in the gut mu-

cosa which may subsequently inﬂuence immune responses in

other tissues can be the main inﬂuential factor (Lammers et al.,

2003; Pohjavuori et al., 2004; Prescott et al., 2005). Although

evidence supporting probiotic efﬁcacy against atopic diseases is

quite convincing, further studies investigating the mechanisms

of disease pathogenesis are required.

COSMETIC APPROACH OF THE PROBIOTICS

REGARDING THE SKIN

To date, only a few specialized suppliers propose primarily

ultrasound-inactivated bacterial extracts from lactic bacteria or

yeasts for potential use in cosmetic products (Gu´

eniche et al.,

2010b). Nowadays, recent studies have demonstrated the suc-

cessful development of a prebiotic cosmetic approach to balance

the composition of the cutaneous microbiota (Simmering and

Breves, 2009). In these studies skin microbiota has been ana-

lyzed by ﬂuorescence in situ hybridization method (Bockm¨

uhl

et al., 2006). In this method, drawbacks of cultural methods

are avoided and the direct observation of bacteria is allowed

(Harmesen et al., 2000).

It has been observed that twice daily using of a cosmetic

product containing selected plant extracts from either Ginseng

or Black currant or pine to human skin for a total of three weeks

was effective in preventing the growth of P. acnes, whereas co-

agulase negative staphylococci were not impressed (Bockm¨

uhl

et al., 2006). It can be concluded that it is totally feasible to

ameliorate the composition of the skin microbiota and to re-

strict or reduce the growth of pathogenic species and at the

same time to preserve and stimulate the growth of beneﬁcial

bacteria. Accordingly, such a probiotic cosmetic approach is

obviously preferable to antibacterial cosmetic products which

unselectively decrease bacterial growth using antibiotics or an-

timicrobial agents (Holland and Bojar, 2002). Gueniche (2010)

disclosed methods directed to the cosmetic use of an effective

amount of at least one probiotic microorganism especially from

the genus Lactobacillus and/or Biﬁdobacterium, or a fraction

thereof and/or a metabolite thereof, as an active agent for lim-

iting, preventing or treating skin irritation, and/or irritative skin

disorders (Gueniche, 2010).

Environmental stress such as UV irradiation may cause ox-

idative stress in exposed skin.

Both UVB and UVA light can induce the generation of re-

active oxygen or nitrogen species (ROS/RNS) in the skin (Xu

and Fisher, 2005). Increased ROS/RNS production induced by

UV light alters gene and protein structure and function, lead-

ing to skin damage (Ritti´

e and Fisher, 2002). Many evidences

indicate that probiotics may be helpful as antioxidant agents,

both in vitro and in vivo (Lin and Chang, 2000) and in some stud-

ies probiotics have been reported to exert systemic protection

from oxidative stress and decrease human low-density lipopro-

tein oxidation (Peguet-Navarro et al., 2008; Bouilly-Gauthier

et al., 2010). It has been concluded that probiotics represent a

useful therapeutic tool for the prevention of epidermal oxidative

stress either via the topical route or via ingestion (Cinque et al.,

2011).

Probiotics’ ability to act as antioxidant can be attributed to

the presence of antioxidant enzymes such as superoxide dismu-

tase (Shen et al., 2010) to the release of antioxidant compounds

such as glutathione (Peran et al., 2006) and to the production

of extracellular polysaccharide biomolecules (Kodali and Sen,

2008). Considering the role of nitric oxide (NO) in inﬂamma-

tory conditions, L. brevis (having arginine deiminase) metabo-

lize arginine to citrulline and ammonia and subsequently it can

inhibit NO generation by competing with nitric oxide synthase

(NOS) for the same substrate, arginine (Di Marzio et al., 2001).

De Simone (2003) revealed the use of bacteria such as L. brevis

endowed with arginine deiminase to induce apoptosis and/or

reduce an inﬂammatory reaction, and pharmaceutical composi-

tions containing such bacteria, including creams and ointments

(De Simone, 2003). Also, it has been indicated that the presence

of L. brevis extracts in cell culture strongly inhibited inducible

NOS activity, IFN-g/PGE2 production, and MMP activity in

LPS-activated macrophages (Della Riccia et al., 2007).

Gu´

eniche (2010) reported three potential mechanisms may

account for the effect of Biﬁdobacterium lysate on skin sensitiv-

ity including a direct action by inhibiting the release of neuro-

mediators involved in sensitivity phenomena, a direct action

by decreasing neurogenic inﬂammation frequently associated

with sensitive skin symptoms and an indirect action by improv-

ing skin barrier function and protecting neurones from external

stimuli (Gu´

eniche et al., 2010b). Baba et al. (2006) reported that

L. helveticus-fermented milk was able to promote differentiation

of cultured normal human epidermal keratinocytes by enhancing

production of the differentiation-related element proﬁlaggrin, a

precursor of a natural moisturizing factor that controls normal

epidermal hydration and ﬂexibility (Baba et al., 2006).

Some preliminary researches have suggested that there

could be a link between probiotics and the youthfulness of

the skin. Biﬁdobacterial species may enhance the production

of hylauronic acid in the skin. Hylauronic acid is involved

in the elasticity of the skin (Tannis, 2008). Two studies have

tested the ability of a biﬁdobacteria-fermented soy milk extract

Downloaded by [University of Maine - Orono] at 03:58 25 April 2015

1234 M. R. ROUDSARI ET AL.

to stimulate hylauronic acid and improve properties of the

skin. The results showed that there was an improvement in the

appearance of the skin (Miyazaki, 2003, 2004).

EFFECTS OF PREBIOTICS ON THE SKIN

Prebiotics have been deﬁned as non-digestible food ingredi-

ents that beneﬁcially affect the host by selectively stimulating

the growth and/or activity of one, or a limiting number of, bac-

teria in the colon (Mohammadi and Mortazavian, 2010; Heydari

et al., 2011). Manipulation of the composition and function of

the skin microbiota by prebiotic strategies (in contrast to antibi-

otics), may allow selective inhibition of detrimental and at the

same time preservation and stimulation of beneﬁcial bacteria,

is therefore of obvious interest in dermatology (Cogen et al.,

2008). Studies have suggested that prebiotics can modulate the

immune system and prevent allergic disorders (Arslanoglu et al.,

2008). In the other words, prebiotics are potentially important

regulators of immune response and have been used in the pre-

vention and treatment of the immune-mediated disorders such

as allergies (Holma et al., 2011). Prebiotics may modulate the

immune system directly through ligation of carbohydrate or

pattern recognition receptors on immune and epithelial cells

(Seifert and Watzl, 2007; Roberfroid et al., 2010).

Prebiotic oligosaccharides have been shown to reduce the

incidence of atopic dermatitis when given to infants at risk for

atopy during the ﬁrst six months of age (Moro et al., 2006). Sev-

eral randomized controlled trials have pointed toward a positive

effect of synbiotics and prebiotics on the course of atopic der-

matitis in older children (Passeron et al., 2006) and it has been

found that both groups had a signiﬁcant reduction in the SCO-

RAD (severity scoring of atopic dermatitis) score after three

months. In the study of Passeron and Lacour (2005) children

with atopic dermatitis receiving placebo treatment improved

signiﬁcantly within a much shorter than expected time. They

used cellulose and maltose dextran as placebo, which could

have a prebiotic effect thus explaining the improvement seen in

the placebo group (Passeron and Lacour, 2005). Kukkonen et al.

(2007) used a combination of four probiotics, including two Lac-

tobacillus species in pregnant women carrying high risk children

for two to four weeks before delivery. In their study the infants

received the same probiotics plus galacto-oligosaccharides for

six months. Their results suggest an inverse association between

atopic diseases and colonization of the gut by probiotics. This

study demonstrated a reduction in eczema that was stronger for

the subgroup with atopic eczema (Kukkonen et al., 2007). Also

they concluded that probiotics especially affect IgE-associated

dermatitis is also supported by the ﬁndings that boys beneﬁted

from the treatment more than did girls and the boys’ total IgE

level was also higher. Similar results have been reported in other

studies (Kukkonen et al., 2008).

It has been reported that consumption of galactooligosaccha-

rides together with probiotics (mixture of L. rhamnosus GG,

L. rhamnosus 29 LC705, Propionibacterium freudenreichii ssp.

Healthful

effects of

prebiotics

on the skin

Increasing

probiotic

efficiency

Immuno-

modulation

(regulating

immune

response)

Reducing

transepider

mal water

loss (on the

skin)

Barrier to

harmful

environmenta

l factors that

are in contact

with the skin

Figure 3 Main mechanisms for healthful effects of prebiotics on the skin.

shermanii JS, and B. breve Bb-99) stimulates the in vitro pe-

ripheral blood mononuclear cell proliferation and interferon γ

production (Holma et al., 2011). As it was previously discussed,

the increase in interferon γwas directly proportional to the de-

crease in the severity of atopic dermatitis (Prescott et al., 2005).

A number of studies have found conﬂicting results concerning

the effect of synbiotics on atopic dermatitis. Some studies have

failed to show efﬁcacy of probiotics or synbiotics in treating

atopic dermatitis (Boyle et al., 2009; Kopp and Salfeld, 2009;

van der Aa et al., 2010). Optimal dosage, frequency and duration

of treatment, single strain or a mixture of probiotics and effects

of prebiotics should be determined because different probiotic

strains vary in their ability to modulate the immune system (Gill

and Prasad, 2008).

Researches have revealed that prebiotics help to balance the

composition of the skin’s microﬂora by inhibiting the growth

of P. acnes and in the mean time preserving the growth of

beneﬁcial bacteria such as Staphylococcus epidermidis, which is

regarded as a commensal bacterium that serves to protect human

skin from infections (Krutmann, 2009). Main mechanisms for

healthful effects of prebiotics on the skin are presented in Fig. 3.

CONCLUSION

Recent researches about health effects of probiotics are hope-

fully favorable. They have a potential role in the prevention and

treatment of skin diseases such as atopic dermatitis. However,

the articles regarding this matter are unanimous that more evi-

dences are needed to prove the impact of probiotics in the treat-

ment of skin diseases especially allergic disorders. Application

Downloaded by [University of Maine - Orono] at 03:58 25 April 2015

HEALTH EFFECTS OF PROBIOTICS ON THE SKIN 1235

of the probiotic bacteria to the skin may provide a protective

shield, similar to a physical barrier. This so-called bacterial

interference, through competitive inhibition of binding sites, is

thought to prevent colonization by other, potentially pathogenic,

bacterial strains. It is necessary to identify other probiotic strains

or combinations of strains that could potentially show efﬁcacy.

The effects of probiotics are strain-speciﬁc, and also depend

on the immunological condition of the host. Furthermore, pro-

biotic combinations should be planned using careful in vitro

preclinical studies on their properties and strain interactions,

prior to proceeding to clinical trials in humans. Further investi-

gations are required, in vitro and in clinical trials, with different

species and strains of probiotic microorganisms in relevance

to their effects on the skin, investigating their modes of action

and considerably more supporting evidence beyond what is cur-

rently provided in this review. Also, customers should be more

aware of the healthful role of probiotics in skin-therapy. This

important role could be implemented via planning by national

health organizations in the countries of use and through proper

advertisements by media.

REFERENCES

Abrahamsson, T., Jakobsson, T., Bottcher, M., Fredrikson, M., Jenmalm, M.

and Oldaeus, N. B. G. (2007). Probiotics in prevention of IgE-associated

eczema: A double-blind, randomized, placebo-controlled trial. J. Allergy Clin.

Immunol. 119:1174–1180.

Adebamowo, C. A., Spiegelman, D., Berkey, C. S., Danby, F. W., Rockett, H. H.,

Colditz, G. A., Willett, W. C. and Holmes, M. D. (2006). Milk consumption

and acne in adolescent girls. Dermatol. Online J. 12:1.

Adebamowo, C. A., Spiegelman, D., Berkey, C. S., Danby, F. W., Rockett, H. H.,

Colditz, G. A. Willett, W. C. and Holmes, M. D. (2008). Milk consumption

and acne in teenaged boys. J. Am. Acad. Dermatol. 58:787–793.

Adebamowo, C. A., Spiegelman, D., Danby, F. W., Frazier, A. L., Willett, W.

C. and Holmes, M. D. (2005). High school dietary dairy intake and teenage

acne. J. Am. Acad. Dermatol. 52:207–214.

Adkinson, N. F. J., Busse, W. W., Bochner, B. S., Holgate, S. T., Simons, F. E.

R. and Lemanske, R. F. (2009). Middleton’s Allergy: Principles and Practice,

7th ed., Mosby, Philadelphia.

Al-Ghazzewi, F. H. and Tester, R. F. (2009). Effect of konjac glucomannan

hydrolysates and probiotics on the growth of the skin bacterium Propionibac-

terium acnes in vitro. Int. J. Cosmet. Sci. 32:139–142.

Al-Ghazzewi, F. H. and Tester, R. F. (2010). Effect of konjac glucomannan

hydrolysates and probiotics on the growth of the skin bacterium Propionibac-

terium acnes in vitro. Int. J. Cosmet. Sci. 32:139–142.

Alm, J. S. (2002). An anthroposophic lifestyle and intestinal microﬂora in

infancy. Pediatr. Allergy Immunol. 3:402–411.

Anon. (1993). Severity scoring of atopic dermatitis: The SCORAD index: Con-

sensus Report of the European TaskForce on Atopic Dermatitis. Dermatology

186:23–31.

Anon. (2006). FAO/WHO. Guidelines for the Evaluation of Probiotics in Food.

Report of a Joint FAO/WHO Working Group on Drafting Guidelines for the

Evaluation of Probiotics in Food.

Arck, P., Handjiski, B., Hagen, E., Pincus, M., Bruenahl, C., Bienenstock, J.

and Paus, R. (2010). Is there a ‘gut-brain-skin axis’? Exp. Dermatol. 19:401–

405.

Arikawa, J., Ishibashi, M., Kawashima, M., Takagi, Y., Ichikawa, Y. and

Imokawa, G. (2002). Decreased levels of sphingosine, a natural antimicro-

bial agent, may be associated with vulnerability of the stratum corneum from

patients with atopic dermatitis to colonization by Staphylococcus aureus. J.

Invest. Dermatol. 119:433–439.

Arslanoglu, S., Moro, G. E., Schmitt, J., Tandoi, L., Rizzardi, S. and Boehm, G.

(2008). Early dietary intervention with a mixture of prebiotic oligosaccharides

reduces the incidence of allergic manifestations and infections during the ﬁrst

two years of life. J. Nutr. 138:1091–1095.

Baba, H., Masuyama, A. and Takano, T. (2006). Effects of Lactobacillus

helveticus-fermented milk on the differentiation of cultured normal human

epidermal keratinocytes. J. Dairy Sci. 89:2072–2075.

Bard, S., Kroshinsky, D., Solomon, H. and Glick, S. (2008). A prospective

randomized, double-blinded, placebo-controlled pilot study of lactobacillus

GG in the treatment of atopic dermatitis. J. Am. Acad. Dermatol. 53:S620.

Baur, M., Breton, L., Couzy, F. and Gueniche, A. (2003). Use of Probiotic Lactic

Acid Bacteria for Balancing the Skin’s Immune System. 20040013706.

Bernet-Camard, M. F., Lievin, V., Brassart, D., Neeser, J. R., Servin, A. L. and

Hudault, H. (1997). The human Lactobacillus acidophilus strain LA1 secretes

a nonbacteriocin antibacterial substance(s) active in vitro and in vivo. Appl.

Environ. Microbiol. 63:2747–2753.

Bernstein, E. F., Brown, D. B., Schwarz, M. D., Kaidbey, K. and Ksenzenko, S.

M. (2004). The polyhydroxy acid gluconolactone protects against ultraviolet

radiation in an in vitro model of cutaneous photoaging. Dermatol. Surg.

30:189–196.

Bockm¨

uhl, D., Jasoy, C., Nieveler, S., Scholtyssek, R., Wadle, A. and

Waldmann-Laue, M. (2006). Prebiotic cosmetics: An alternative to antibac-

terial products. IFSSC Mag. 9:1–5.

Bouilly-Gauthier, D., Jeannes, C., Maubert, Y., Duteil, L., Queille-Roussel, C.,

Piccardi, N., Montastier, C., Manissier, P., Pierard, G. and Ortonne, J. P.

(2010). Clinical evidence of beneﬁts of a dietary supplement containing pro-

biotic and carotenoids on ultraviolet-induced skin damage. Br. J. Dermatol.

163:534–543.

Bowe, W. P., Filip, J. C., Dirienzo, J. M., Volgina, A. and Margolis, D. J.

(2006). Inhibition of propionibacterium acnes by bacteriocin-like inhibitory

substances (BLIS) produced by Streptococcus salivarius. J. Drugs Dermatol.

5:868–870.

Bowe, W. P. and Logan, A. C. (2010). Clinical implications of lipid peroxidation

in acne: Old wine in new bottles. Lipids Health Dis.9:141–151.

Bowe, W. P. and Logan, A. C. (2011). Acne vulgaris, probiotics and the gut-

brain-skin axis—back to the future? Gut Pathogens 3:1–11.

Boyle, R. J., Bath-Hextall, F. J., Leonardi-Bee, J. and Al., E. (2009). Probi-

otics for the treatment of eczema: A systematic review. Clin. Exp. Allergy

39:1117–27.

Boyle, R. J. and Tang,M. L. K. (2006). The role of probiotics in the management

of allergic disease. Clin. Exp. Allergy 36:568–576.

Brouwer, M. L., Wolt-Plompen, S. A. and Dubois, A. E. (2006). No effects of

probiotics on atopic dermatitis in infancy: A randomized placebo-controlled

trial. Clin. Exp. Allergy 36:899–906.

Bunselmeyer, B. and Buddendick, K. (2010). Probiotics and prebiotics-

prevention and therapy in atopic eczema. In: Bioactive Foods in Promoting

Health: Probiotics and Prebiotics. Watson, R. R. and Preedy, V. R., Eds.,

Elsevier, USA.

Caffarelli, C., Cavagni,G., Menzies, I. S., Bertolini, P. and Atherton, D. J. (1993).

Elimination diet and intestinal permeability in atopic eczema: A preliminary

study. Clin. Exp. Allergy 23:28–31.

Caramia, G., Atzei, A. and Fanos, V. (2008). Probiotics and the skin. Clin.

Dermatol. 26:4–11.

Carroll, C. L., Balkrishnan, R., Feldman, S. R., Fleischer, A. B. J. and Manuel,

J. C. (2005). The burden of atopic dermatitis: Impact on the patient, family,

and society. Pediatr. Dermatol. 22:192–199.

Cazzola, M., Tompkins, T. A. and Matera, M. G. (2010). Immunomodulatory

impact of a synbiotic in T(h)1 and T(h)2 models of infection. Ther. Adv.

Respir. Dis. 4:259–270.

Chapat, L., Chemin, K., Dubois, B., Bourdet-Sicard, R. and Kaiserlian, D.

(2004). Lactobacillus casei reduces CD8+T cell-mediated skin inﬂamma-

tion. Eur. J. Immunol. 34:2520–2528.

Charman, C. and Williams, H. (2000). Outcome measures of disease severity in

atopic eczema. Arch. Dermatol. 136:763–769.

Downloaded by [University of Maine - Orono] at 03:58 25 April 2015

1236 M. R. ROUDSARI ET AL.

Chiba, K. (2007). Development of functional cosmetic ingredients using lactic

acid bacteria in Japan. Jpn. J. Lactic Acid Bact. 18:105–112.

Cinque, B., Palumbo, P., La Torre, C., Melchiorre, E., Corridoni, D., Miconi,

G., Di Marzio, L., Cifone, M. G. and Giuliani, M. (2010). Probiotics in aging

skin. In: Textbook of Aging Skin, Farage, M. A., Miller, K. W., and Maibach,

H. I., eds. Springer, Berlin.

Cinque, B., Torre, C., Melchiorre, E., Marchesani, G., Zoccali, G., Palumbo,

P., Marzio, L. D., Masci, A., Mosca, L., Mastromarino, P., Giuliani, M.

and Cifone, M. G. (2011). Use of probiotics for dermal applications. In:

Probiotics, Microbiology Monographs. Liong, M.-T., Ed., Springer Verlag,

Berlin, Heidelberg.

Coconnier, M. H., Lievin, V., Hemery, E. and Servin, A. L. (1998). Antag-

onistic activity against Helicobacter infection in vitro and in vivo by the

human Lactobacillus acidophilus strain LB. Appl. Environ. Microbiol.

64:4573–4580.

Cogen, A. L., Nizet, V. and Gallo, R. L. (2008). Skin microbiota: A source of

disease or defense? Br. J. Dermatol. 158:442–455.

Cosseau, C., Devine, D. A., Dullaghan, E., Gardy, J. L., Chikatamarla, A.,

Gellatly, S., Yu, L. L., Pistolic, J., Falsaﬁ, R., Tagg, J. and Hancock, R. E.

W. (2008). The commensal Streptococcus salivarius K12 downregulates the

innate immune responses of human epithelial cells and promotes hostmicrobe

homeostasis. Infect. Immunol. 76:4163–4175.

Cross, M. L. (2002). Immunoregulation by probiotic lactobacilli: Pro-Th1

signals and their relevance to human health. Clin. Appl. Immunol. Rev.

3:115–125.

De Simone, C. (2003). Use of Bacteria Endowed with Arginine Deiminase to In-

duce Apoptosis and/or Reduce an Inﬂammatory Reaction and Pharmaceutical

or Dietetic Compositions Containing Such Bacteria.

del Giudice Jr, M. M., De Luca, M. G. and Capristo, C. (2002). Probiotics

and atopic dermatitis. A new strategy in atopic dermatitis. Digest. Liver Dis.

34:S68–S71.

Della Riccia, D. N., Bizzini, F., Perilli, M. G., Polimeni, A., Trinchieri, V.,

Amicosante, G. and Cifone, M. G. (2007). Anti-inﬂammatory effects of Lac-

tobacillus brevis (CD2) on periodontal disease. Oral Dis. 13:376–385.

Di Marzio, L., Centi, C., Cinque, B., Masci, S., Giuliani, M. and Arcieri, A.

(2003). Effect of the lactic acid bacterium streptococcus thermophilus on

stratum corneum ceramide levels and signs and symptoms of atopic dermatitis

patients. Exp. Dermatol. 12:615–620.

Di Marzio, L., Cinque, B., Cupelli, F., De Simone, C., Cifone, M. G. and

Giuliani, M. (2008). Increase of skin-ceramide levels in aged subjects fol-

lowing a short-term topical application of bacterial sphingomyelinase from

Streptococcus thermophilus. Int. J. Immunopathol. Pharmacol. 21:137–143.

Di Marzio, L., Cinque, B., De Simone, C. and Cifone, M. G. (1999). Effect of

the lactic acid bacterium Streptococcus thermophilus on ceramide levels in

human keratinocytes in vitro and stratum corneum in vivo. J. Invest Dermatol.

113:98–106.

Di Marzio, L., Russo, F. P., D’AL `

o, S., Biordi, L., Ulisse, S., Amicosante, G.,

De Simone, C. and Cifone, M. G. (2001). Apoptotic effects of selected strains

of lactic acid bacteria on a human T leukemia cell line are associated with

bacterial arginine deiminase and/or sphingomyelinase activities. Nutr. Cancer

40:185–196.

Duramad, P., Harley, K. and Lipsett, M. (2006). Early environmental exposures

and intracellular Th1/Th2 cytokine proﬁles in 24-month-old children living

in an agricultural area. Environ. Health Perspect. 114:1916–1922.

Eady, E. A. and Ingham, E. (1994). Propionibacterium acnes-friend or foe? Rev.

Med. Microbiol. 5:163–173.

Elias, P. M. and Choi, E. H. (2005). Interactions among stratum cormeum

defensive functions. Exp. Dermatol. 14:719–726.

Euvrard, S., Kanitakis, J. and Claudy, A. (2003). Skin cancers after organ

transplantation. N. Engl. J. Med. 348:1681–1691.

Farid, R., Ahanchian, H., Jabbari, F. and Moghiman, T. (2011). Effect of a new

synbiotic mixture on atopic dermatitis in children: A randomized-controlled

trial. Iran. J. Pediatr. 21:225–230.

Farmer, S. (2005). Topical Compositions Containing Probiotic Bacillus Bacte-

ria, Spores, and Extracellular Products and Uses Thereof. 14 June 2005 patent

application.

Feingold, K. R. (2007). Thematic review series: Skin lipids. The role of epi-

dermal lipids in cutaneous permeability barrier homeostasis. J. Lipid Res.

48:2531–2546.

Feleszko, W., Jaworska, J., Rha, R. D., Steinhausen, S., Avagyan, A., Jaud-

szus, A., Ahrens, B., Groneberg, D. A., Wahn, U. and Hamelmann, E.

(2007). Probioticinduced suppression of allergic sensitization and airway

inﬂammation is associated with an increase of T regulatory-dependent

mecha-nisms in a murine model of asthma. Clin. Exp. Allergy 37:

498–505.

Fink, L. N. (2010). Induction of regulatory T cells by probiotics: Potential for

treatment of allergy? Clinl. Exper. Allergy 40:5–8.

Flinterman, A. E., Knol, E. F., van Ieperen-van Dijk, A. G., Timmerman, H. M.,

Knulst, A. C., Bruijnzeel-Koomen, C. A., Pasmans, S. G. and van Hoffen,

E. (2007). Probiotics have a different immunomodulatory potential in vitro

versus ex vivo upon oral administration in children with food allergy. Int.

Arch. Allergy Immunol. 143:237–244.

Flohr, C., Pascoe, D. and Williams, H. C. (2005). Atopic dermatitis and

the ehygiene hypothesisf: Too clean to be true? Br. J. Dermatol. 152:

202–216.

Folster-Holst, R., M¨

uller, F., Schnopp, N., Abeck, D., Kreiselmaier, I., Lenz,

T., v on R ¨

uden, U., Schrezenmeir, J., Christophers, E. and Weichenthal, M.

(2006). Prospective, randomized controlled trial on Lactobacillus rhamno-

sus in infants with moderate to severe atopic dermatitis. Br. J. Dermatol.

155:1256–1261.

Fu, Y. R., Yi, Z. J., Pei, J. L. and Guan, S. (2010). Effects of Biﬁdobacterium

biﬁdum on adaptive immune senescence in aging mice. Microbiol. Immunol.

54:578–583.

Fukushima, Y., Kawata, Y., Mizumachi, K., Kurisaki, J. and Mitsuoka, T.(1999).

Effect of biﬁdobacteria feeding on fecal ﬂora and production of immunoglob-

ulins in lactating mouse. Int. J. Food Microbiol. 46: 193–197.

Ghadimi, D., F¨

olster-Holst, R., de Vrese, M., Winkler, P., Heller, K. J.

and Schrezenmeir, J. (2008). Effects of probiotic bacteria and their ge-

nomic DNA on TH1/TH2-cytokine production by peripheral blood mononu-

clear cells (PBMCs) of healthy and allergic subjects. Immunobiology 213:

677–692.

Gill, H. and Prasad, J. (2008). Probiotics, immunomodulation, and health ben-

eﬁts. Adv. Exp. Med. Biol. 606:423–454.

Gillor, O., Etzion, A. and Riley, M. A. (2008). The dual role of bacteriocins as

anti- and probiotics. Appl. Microbiol. Biotechnol. 81:591–606.

Grice, E. A., Kong, H. H., Renaud, G., Young, A. C., Bouffard, G. G. and

Blakesley, R. W. (2008). A diversity proﬁle of the human skin microbiota.

Genome Res.18:1043–1050.

Gromert, N. and Axelsson, I. (2009). Dietary supplementation with Lactobacil-

lus reuteri ATCC 55730 and its effect on atopic eczema in childhood. In:

Proceedings for the 42nd European Society for Pediatric Gastroenterology

Hepatology and Nutrition (ESPGHAN).

Gr¨

uber, C., Wendt, M., Sulser, C., Lau, S., Kulig, M., Wahn, U., Werfel, T.

and Niggemann, B. (2007). Randomized, placebo-controlled trial of Lacto-

bacillus rhamnosus GG as treatment of atopic dermatitis in infancy. Allergy

62:1270–1276.

Guenche, A., Benyacoub, J., Buetler, T. M., Smola, H. and Blum, S. (2006).

Supplementation with oral probiotic bacteria maintains cutaneous immune

homeostasis after UV exposure. Eur. J. Dermatol. 16:511–517.

Gueniche, A. (2010a). Use of Probiotic Microorganisms to Limit Skin Irritation.

US Patent, US20100226892.

Gueniche, A., Bastien, P., Ovigne, J. M., Kermici, M., Courchay, G. and Cheva-

lier, V. (2010b). Biﬁdobacterium longum lysate, a new ingredient for reactive

skin. Exp. Dermatol. 19:1–8.

Gueniche, A., Benyacoub, J., Blum, S., Breton, L. and Castiel, I. (2009). Pro-

biotics for skin beneﬁts. In: Nutritional Cosmetics: Beauty from Within.

Tabor, A. and Blair, R. M., Eds., William Andrew Applied Science Publish-

ers/Elsevier.

Gueniche, A., Benyacoub, J., Breton, L., Bastien, P., Bureau-Fanz, I., Blum,

S. and Leclaire, J. (2007). A combination of Lactobacillus paracasei CNCM

I-2116 and Biﬁdobacterium lactis CNCM I-3446 probiotic strains decreases

skin reactivity. J. Invest. Dermatol. 102:S17.

Downloaded by [University of Maine - Orono] at 03:58 25 April 2015

HEALTH EFFECTS OF PROBIOTICS ON THE SKIN 1237

Gueniche, A., Benyacoub, J., Buetler, T. M., Smola, H. and Blum, S. (2006).

Supplementation with oral probiotic bacteria maintains cutaneous immune

homeostasis after UV exposure. Eur. J. Dermatol. 16:511–517.

Gueniche, A., Benyacoub, J., Philippe, D., Bastien, P., Kusy, N. and Breton,

L. (2010a). Lactobacillus paracasei CNCM I-2116 (ST11) inhibits substance

P-induced skin inﬂammation and accelerates skin barrier function recovery

in vitro. Eur. J. Dermatol. 20:731–737.

Hacini-Rachinel, F., Gheit, H., Le Luduec, J. B., Dif, F., Nancey, S. and Kaiser-

lian, D. (2009). Oral probiotic control skin inﬂammation by acting on both

effector and regulatory T cells. PLoS One 4:4903–4911.

Halken, S. (2004). Prevention of allergic disease in childhood: Clinical and

epidemiological aspects of primary and secondary allergy prevention. Pediatr.

Allergy Immunol. 4–5:9–32.

Halper, J., Leshin, L. S., Lewis, S. J. and Li, W. I. (2003). Wound healing and

angiogenic properties of supernatants from Lactobacillus cultures. Exp. Biol.

Med. 228:1329–1337.

Halvarsson, K. and Lod´

en, M. (2007). Increasing quality of life by improving

the quality of skin in patients with atopic dermatitis. Int. J. Cosmet. Sci.

29:69–83.

Hancox, J. G., Sheridan, S. C., Feldman, S. R. and Fleischer, A. B. (2004).

Seasonal variation of dermatologic disease in the USA: A study of ofﬁce

visits from 1990 to 1998. Int. J. Dermatol. 43:6–11.

Hansen, J. E. and Jespersen, L. K. (2010). Woundor Tissue Dressing Comprising

Lactic Acid Bacteria. 10 June 2010 patent application.

Harmesen, H. J., Gibson, G. R., Elfferich, P., Raanags, G. C., Wildeboer-Veloo,

A. C. and Argaiz, A. (2000). Comparison of viable ell counts and ﬂuorescence

in situ hybridization using speciﬁc rRNA-based probes for the quantiﬁcation

of human feel bacteria. FEMS Microbiol. Lett. 183:125–129.

Hattori, K., Yamamoto, A. and Sasai, M. (2003). Effects of administration of

biﬁdobacteria on fecal microﬂora and clinical symptoms in infants with atopic

dermatitis. 52, 20–30.

Hessle, C., Hanson, L. A. and Wold, A. E. (1999). Lactobacilli from human

gastrointestinal mucosa are strong stimulators of IL-12 production. Clin.

Exp. Immunol. 116:276–282.

Heydari, S., Mortazavian, A. M., Ehsani, M. R., Mohammadifar, M. A., Ez-

zatpanah, H. and Sohrabvandi, S. (2011). Biochemical, microbiological and

sensory characteristics of probiotic yougurt containing various prebiotic or

ﬁber compounds. Ital. J. Food Sci. 23:153–163.

Holland, K. T. and Bojar, R. A. (2002). Cosmetics. What is their inﬂuence on

the skin microﬂora? Am. J. Clin. Dermatol. 3:445–449.

Holma, R., Kekkonen, R. A., Hatakka, K. H., Poussa, T., Vaarala, O., Adler-

creutz, H. and Korpela, R. (2011). Consumption of Galactooligosaccharides

Together with Probiotics Stimulates the in vitro Peripheral Blood Mononu-

clear Cell Proliferation and IFNγProduction in Healthy Men. ISRN Immunol-

ogy,2011: 1–6.

Hou, J. W., Yu, R. C. and Chou, C. C. (2000). Changes in some components of

soymilk during fermentation with biﬁdobacteria. Food Res. Int. 33:393–397.

Isolauri, E., Arvola, T. and Sut¨

as, Y. (2000). Probiotics in the management of

atopic eczema. Clin. Exp. Allergy 30:1604–1610.

Isolauri, E., Pelto, L., Nuutila, J., Majamaa, H., Lilius, E.-M. and Salminen,

S. (1997). Altered expression of IgG and complement receptors indicates a

signiﬁcant role of phagocytes in atopic dermatitis. J. Allergy Clin. Immunol.

99: 707–713.

Isolauri, E., Sutas, Y., Kankaanpaa, P., Arvilommi, H. and Salminen, S. (2001).

Probiotics: Effects on immunity. Am.J.Clin.Nutr.73:444S–450S.

Ji, G. E. (2009). Probiotics in primary prevention of atopic dermatitis. For u m .

Nutr. 61:117–128.

Johnson, C. C., Ownby, D. R. and Alford, S. H. (2005). Antibiotic exposure

in early infancy and risk for childhood atopy. J. Allergy Clin. Immunol.

115:1218–1224.

Jones, M. L., Ganopolsky, J. G., Labbe, A. and Prakash, S. (2010). A novel nitric

oxide producing probiotic patch and its antimicrobial efﬁcacy: Preparation

and in vitro analysis. Appl. Microbiol. Biotechnol. 87:509–516.

Kalliom¨

aki, M., Salminen, S. and Arvilommi, H. (2001). Probiotics in primary

prevention of atopic disease: A randomised placebo-controlled trial. Lancet

357:1076–1079.

Kalliom¨

aki, M., Salminen, S. and Poussa, T. (2003). Probiotics and prevention

of atopic disease: R-year follow-up of a randomised placebo-controlled trial.

Lancet 361:1869–1871.

Kalliom¨

aki, M., Salminen, S., Poussa, T. and Isolauri, E. (2007). Probiotics

during the ﬁrst 7 years of life: A cumulative risk reduction of eczema in a ran-

domized, placebo-controlled trial. J. Allergy Clin. Immunol. 119:1019–1021.

Kang, S. H., Kim, J. U., Imm, J. Y., Oh, S. and Kim, S. H. (2006). The effects of

dairy processes and storage on insulin-like growth factor-I (IGF-I) content in

milk and in model IGF-I-fortiﬁed dairy products. J. Dairy Sci. 89:402–409.

Kang, B. S., Seo, J. G., Lee, G. S., Kim, J. H., Kim, S. Y., Han, Y. W. and Al.,

E. (2009). Antimicrobial activity of enterocins from Enterococcus faecalis

SL-5 against Propionibacterium acnes, the causative agent in acne vulgaris,

and its therapeutic effect. J. Microbiol. 47:101–109.

Kankaanpaa, P., Sutas, Y., Arvilommi, H., Salminen, S. and Isolauri, E. (1998).

Comparison of antiproliferative effects of probiotic cell extracts and gluco-

corticoids. Gastroenterol. Int. 11:S139–S146.

Kankaanpaa, P. E., Yang, B., Kallio, H. P., Isolauri, E. and Salminen, S. J.

(2002). Inﬂuence of probioticsupplementedinfant formulaon composition of

plasma lipidsin atopicinfants. J. Nutr. Biochem. 13:364–369.

Karimi, R., Mortazavian, A. M. and Amiri-Rigi, A. (2012). Selective enumera-

tion of probiotic microorganisms in cheese. Food Microbiol. 29:1–9.

Karimi, R., Mortazavian, A. M. and Cruz, A. G. (2011). Viability of probiotic

microorganisms in cheese during production and storage: A review. Dairy

Sci. Technol. 91:283–308.

Kidd, P. (2003). Th1/Th2 balance: The hypothesis, its limitations, and implica-

tions for health and disease. Altern. Med. Rev. 8: 223–246.

Kim, J., Ko, Y., Park, Y. K., Kim, N. I., Ha, W. K. and Cho, Y. (2010). Dietary

effect of lactoferrinenriched fermented milk on skin surface lipid and clinical

improvement of acne vulgaris. Nutr. Cancer 26:902–909.

Kim, J. Y., Kwon, J. H., Ahn, S. H., Lee, S. I., Han, Y. S., Choi, Y. O., Lee, S.

Y., Ahn, K. M. and Ji, G. E. (2009). Effect of probiotic mix (Biﬁdobacterium

biﬁdum, Biﬁdobacterium lactis, Lactobacillus acidophilus) in the primary

prevention of eczema: A double-blind, randomized, placebo-controlled trial.

Pediatr. Allergy Immunol. 21:e386–e393.

Kirjavainen, P. V., Arvola, T., Salminen, S. J. and Isolauri, E. (2002). Aberrant

composition of gut microbiota of allergic infants. a target of biﬁdobacterial

therapy at weaning? Gut 51, 51–55.

Kirjavainen, P. V., Apostolou, E., Salminen, S. J. and Isolauri, E. (1999). New

aspects of probiotics - a novel approach in the management of food allergy.

Allergy 54:909–915.

Kirjavainen, P. V., Salminen, S. J. and Isolauri, E. (2003). Probiotic bacteria in

the management of atopic disease: Underscoring the importance of viability.

J. Pediatr. Gastroenterol. Nutr. 36:223–227.

Kliegman, R. M., Behrman, R. E., Jenson, H. B. and Stanton, B. F. (2007).

Nelson Textbook of Pediatrics. Saunders, Philadelphia.

Kodali, V. P. and Sen, R. (2008). Antioxidant and free radical scavenging ac-

tivities of an exopolysaccharide from a probiotic bacterium. Biotechnol. J.

3:245–251.

Kopp, M., Hennemuth, I., Heinzmann, A. and Urrbanek, R. (2008). Random-

ized, double-blind, placebo-controlled trial for primary prevention: No clini-

cal effects of Lactobacillus GG supplementation. Pediatrics 121:1–7.

Kopp, M. V. and Salfeld, P. (2009). Probiotics and prevention of allergic disease.

Curr. Opin. Clin. Nutr. Metab. Care. 12:298–303.

Korbekandi, H., Mortazavian, A. M. and Iravani, S. (2011). Technology and

stability of probiotic in fermented milks. In: Probiotic and Prebiotic Foods:

Technology, Stability and Beneﬁts to the Human Health. Shah, N. P., Ed.,

Nova Science Publishers, New York.

Kruisselbrink, A., Bak-Glashouwer, M. J. H. D., Havenith, C. E., Thole, J. E.

and Janssen, R. (2001). Recombinant Lactobacillus plantarum inhibits house

dust mite-speciﬁc T-cell responses. Clin. Exp. Immunol. 126:2–8.

Krutmann, J. (2009). Pre- and probiotics for human skin. J. Dermatol. Sci.

54:1–5.

Kuitunen, M., Kukkonen, K., Juntunen-Backman, K., Korpela, R., Poussa, T.,

Tuure, T., Haahtela, T. and Savilahti, E. (2009). Probiotics prevent IgE-

associated allergy until age 5 years in cesarean-delivered children but not in

the total cohort. J. Allergy Clin. Immunol. 123:335–341.

Downloaded by [University of Maine - Orono] at 03:58 25 April 2015

1238 M. R. ROUDSARI ET AL.

Kukkonen, K., Savilahti, E. and Haahtela, T. (2008). Long-term safety and

impact on infection rates of postnatal probiotic and prebiotic (synbiotic)

treatment: Randomized, double-blind, placebo-controlled trial. Pediatrics

122:8–12.

Kukkonen, K., Savilahti, E., Haahtela, T., Juntunen-Backman, K., Korpela,

R., Poussa, T., Tuure, T. and Kuitunen, M. (2007). Probiotics and prebi-

otics galacto-oligosaccharides in the prevention of allergic disease: A ran-

domized, double-blind, placebo-controlled trial. J. Allergy Clin. Immunol.

119:192–198.

Kummeling, I., Stelma, F. F. and Dagnelie, P. C. (2007). Early life exposure to

antibiotics and the subsequent development of eczema, wheeze, and allergic

sensitization in the ﬁrst 2 years of life: The KOALA Birth Cohort Study.

Pediatrics 119:225–231.

Kunz, B., Oranje, A. P. and Labreze, L. (1997). Clinical validation and guidelines

for the SCORAD index: Consensus report of the European Task Force on

Atopic Dermatitis. Dermatology 195:9–10.

Lakshini, A. V. (1998). Riboﬂavin metabolism-relevance to human nutrition.

Ind. J. Med. Res. 108:182–190.

Lammers, K. M., Brigidi, P. and Vitali, B. (2003). Immunomodulatory effects of

probiotic bacteria DNA: Il-1 and IL-10 response in human peripheral blood

mononucelar cells. FEMS Immunol. Med. Microbiol. 38:165–172.

Lambers, H., Piessens, S., Bloem, A., Pronk, H. and Finkel, P. (2006). Natural

skin surface pH is on average below 5, which is beneﬁcial for its resident

ﬂora. Int. J. Cosmet. Sci. 28:359–370.

Laughter, D., Istvan, J. A., Tofte, S. J. and Haniﬁn, J. M.. (2000). The preva-

lence of atopic dermatitis in Oregon schoolchildren. J. Am. Acad. Dermatol.

43:649–655.

Lee, W. J., Jung, H. D., Lee, H. J., Kim, B. S., Lee, S. J. and Kim Do, W.

(2008b). Inﬂuence of substance-P on cultured sebocytes. Arch. Dermatol.

Res. 300:311–316.

Lee, T. T., Morisset, M., Astier, C., Moneret-Vautrin, D. A., Cordebar, V.,

Beaudouin, E., Codreanu, F., Bihain, B. E. and Kanny, G. (2007). Contam-

ination of probiotic preparations with milk allergens can cause anaphylaxis

in children with cow’s milk allergy. J. Allergy Clin. Immunol. 119:746–

747.

Lee, J., Seto, D. and Bielory, L. (2008a). Meta-analysis of clinical trials of pro-

biotics for prevention and treatment of pediatric atopic dermatitis. J. Allergy

Clin. Immunol. 121:116–121.

Leyden, J. J., Mcginley, K. J. and Bowels, B. (1998). Propionibacterium acnes

colonization in acne and nonacne. Dermatology 196:55–58.

Leyden, J. J., Mcginley, K. J., Nordstrom, K. M. and Webster, G. F. (1987).

Skin microﬂora. J. Invest. Dermatol. 88:65s–72s.

Lin, M. Y. and Chang, F. J. (2000). Antioxidative effect of intestinal bacteria

Biﬁdobacterium longum ATCC 15708 and Lactobacillus acidophilus ATCC

4356. Dig. Dis. Sci. 45:1617–1622.

Ling, E. M., Smith, T., Nguyen, X. D., Pridgeon, C., Dallman, M. and Arbery,

J. (2004). Relation of CD41CD251 regulatory T-cell suppression of allergen-

driven T-cell activation to atopic status and expression of allergic disease.

Lancet 363:608–615.

Ly, N. P., Litonjua, A., Gold, D. R. and Celed ´

on, J. C. (2011). Gut microbiota,

probiotics, and vitamin D: Interrelated exposures inﬂuencing allergy, asthma,

and obesity? J. Allergy Clin. Immunol. 127:1087–1094.

Ma, D., Forsythe, P. and Bienenstock, J. (2004). Live Lactobacillus reuteri is

essential for the inhibitory effect on tumour necrosis factor alpha-induced

Interleukin-8 expression. Infect. Immunol. 72:5308–5314.

Macpherson, A. J. and Harris, N. L. (2004). Opinion: Interactions between

commensal intestinal bacteria and the immune system. Nat. Rev. Immunol.

4:478–485.

Majamaa, H. and Isolauri, E. (1997). Probiotics: A novel approach in the man-

agement of food allergy. J. Allergy Clin. Immunol. 99:179–185.

Marchetti, F., Capizzi, R. and Tulli, A. (1987). Efﬁcacy of regulators of the

intestinal bacterial ﬂora in the therapy of acne vulgaris. Clin. Ter. 122:

339–343.

Mauro, T. (2006). SC pH: Measurement, origins, and functions. In: Skin Barrier.

Elias, P. and Feingold, K., Eds., Taylor & Francis, New York.

Melnik, B. C. and Schmitz, G. (2009). Role of insulin, insulin-like growth

factor-1, hyperglycaemic food and milk consumption in the pathogenesis of

acne vulgaris. Exp. Dermatol. 18:833–841.

Metze, D., Kerssten, A., Jurecka, W. and Gebhart, W. (1991). Immunoglobulins

coat microorganisms of skin surface: A comparative immunohistochemical

and ultrastructural study of cutaneous and oral microbial symbionts. J. Invest.

Dermatol. 96:439–445.

Michail, S. (2009). The role of Probiotics in allergic diseases. Allergy Asthma

Clin. Immunol. 5:1–7.

Michail, S., Onady, G., Stolﬁ, A. and Johnson, T. (2008). Efﬁcacy of probiotics

in treatment of pediatric atopic dermatitis a meta-analysis of randomized,

controlled trials. Ann. Allergy Asthma Immunol. 101:508–516.

Miettinen, M., Matikainen, S., Vuopio-Varkila, J., Pirhonen, J., Varkila, K.,

Kurimoto, M. and Julkunen, I. (1998). Lactobacilli and streptococci induce

interleukin-12 (IL-12), IL-18, and gamma interferon production in human

peripheral blood mononuclear cells. Infect. Immunol. 66:6058–6062.

Mikelsaar, M. and Zilmer, M. (2009). Lactobacillus fermentum ME-3 - an

antimicrobial and antioxidative probiotic. Microb. Ecol. Health Dis. 21:1–27.

Miraglia, D. G. M. and De Luca, M. G. (2004). The role of probiotics in the clin-

ical management of food allergy and atopic dermatitis. J. Clin. Gastroenterol.

38:S84–S85.

Miyazaki, K. (2003). Biﬁdobacterium-fermented soy milk extract stimulates

hylauronic acid production in human skin cells and hairless mouse skin. Skin

Pharmacol. Appl. Skin Physiol. 16:108–116.

Miyazaki, K. (2004). Topicalapplication of Biﬁdobacterium-fermented soy milk

extract containing genistein and daidzein improves rheological and physio-

logical properties of skin. J. Cosmet. Sci. 55:473–479.

Mohammadi, R. and Mortazavian, A. M. (2010). Technological aspects of pre-

biotics in probiotic fermented milks. Food Rev. Int. 27:192–212.

Moro, G., Arslanoglu, S. and Stahl, B. (2006). A mixture of prebiotic oligosac-

charides reduces the incidence of atopic dermatitis during the ﬁrst six months

of age. Arch. Dis. Child. 91:814–819.

Moyal, D. and Fourtanier, A. (2004). Acute and chronic effects of UV on skin.

In: Photoaging. Rigel, D. S., Weiss, R. A., Lim, H. W. and Dover, J. S., Eds.,

Marcel Dekker, New York.

Mucid, D. and Salek-Ardekani, S. H. (2009). Regulation of TH17 cells in the

mucosal surfaces. J. Allergy Clin. Immunol. 123:997–1003.

Negoro, T., Orihara, K. and Irahara, T. (2006). Inﬂuence of SNPs in cytokine-

related genes on the severity of food allergy and atopic eczema in children.

Pediatr. Allergy Immunol. 17:583–590.

Netea, M. G., Van der Meer, J. W. and Kullberg, B. J. (2004). Toll-like re-

ceptors as an escape mechanism from the host defense. Trends Microbiol.

12:484–488.

Niers, L., Mart´

ın, R., Rijkers, G., Sengers, F., Timmerman, H., van Uden,

N., Smidt, H., Kimpen, J. and Hoekstra, M. (2009). The effects of selected

probiotic strains on the development of eczema (the PandA study). Allergy

64:1349–1358.

Niers, L., Timmerman, H., Rijkers, G., Van Bleek, G., van Uden, N. and Knol,

E. (2005). Identiﬁcation of strong interleukin-10 inducing lactic acid bac-

teria which down-regulate T helper type 2 cytokines. Clin. Exp. Allergy

35:1481–1489.

Noverr, M. C., Falkowski, N. and Mcdonald, R. A. (2005). Development of

allergic airway disease in mice following antibiotic therapy and fungal mi-

crobiota increase: Role of host genetics, antigen, and interleukin-13. Infect.

Immunol. 73:30–38.

Noverr, M. C. and Huffnagle, G. B. (2004). Does the microbiota regulate im-

mune responses outside the gut? Trends Microbiol.12:562–568.

Noverr, M. C. and Huffnagle, G. B. (2005). The “microﬂora hypothesis” of

allergic diseases. Clin. Exp. Allergy 35:1511–1520.

Ogden, N. S. and Bielory, L. (2005). Probiotics: A complementary approach in

the treatment and prevention of pediatric atopic disease. Curr. Opin. Allergy

Clin. Immunol. 5:179–184.

Oh, S., Kim, S. H., Ko, Y., Sim, J. H., Kim, K. S., Lee, S. H., Park, S. and Kim,

Y. J. (2006). Effect of bacteriocin produced by Lactococcus sp. HY 449 on

skin-inﬂammatory bacteria. Food Chem. Toxicol. 44:552–559.

Downloaded by [University of Maine - Orono] at 03:58 25 April 2015

HEALTH EFFECTS OF PROBIOTICS ON THE SKIN 1239

Osborn, D. and Sinn, J. (2007). Probiotics in infants for prevention of aller-

gic disease and food hypersensitivity [review]. Cochr. Database Syst. Rev.

CD006474.

Ouwehand, A. C. (2007). Antiallergic effects of probiotics. J. Nutr. 137:

794S–797S.

Ouwehand, A. C., B˚

atsman, A. and Salminen, S. (2003). Probiotics for the skin:

A new area of potential application? Letters Appl. Microbiol. 36:327–331.

Ouwehand, A. C., Salminen, S. and Isolauri, E. (2002). Probiotics: An overview

of beneﬁcial effects. Antonie van Leuwenhoek 82:279–289.

Paganelli, R., Ciuffreda, S., Verna, N., Cavallucci, E., Paolini, F., Ramondo, S.

and Di Gioacchino, M. (2002). Probiotics and food-allergic diseases. Allergy

57:97–99.

Passeron, T. and Lacour, J. (2005). Effects of probiotics on atopic dermatitis.

Arch. Dis. Child. 20:171–176.

Passeron, T., Lacour, J. P. and Fontas, E. (2006). Prebiotics and synbiotics: Two

promising approaches for the treatment of atopic dermatitis in children above

2 years. Allergy 61:431–437.

Pavicic, T., Wollenweber, U., Farwick, M. and Korting, H. C. (2007). Anti-

microbial and -inﬂammatory activity and efﬁcacy of phytosphingosine: An

in vitro and in vivo study addressing acne vulgaris. Int. J. Cosmet Sci.

29:181–190.

Peguet-Navarro, J., Dezutter-Dambuyant, C., Buetler, T. M., Leclaire, J., Smola,

H., Blum, S., Bastien, P., Breton, L. and Gueniche, A. (2008). Supplementa-

tion with oral probiotic bacteria protects human cutaneous immune homeosta-

sis after UV exposure-double blind, randomized, placebo controlled clinical

trial. Eur. J. Dermatol. 18:504–511.

Pelto, L., Isolauri, E., Lilius, E.-M., Nuutila, J. and Salminen, S. (1998). Probi-

otic bacteria downregulate the milk-induced inﬂammatory response in milk-

hypersensitive subjects but have an immunostimulatory effect in healthy sub-

jects. Clin. Exp. Allergy 28:1474–1479.

Peˇ

na, J., Rogers, A., Ge, Z., Ng, V., Li, S., Fox, J. and Versalovic, J. (2005). Probi-

otic Lactobacillus spp diminish Helicobacter hepaticus-induced inﬂammatory

bowel disease in Interleukin-10-deﬁcient mice. Infect. Immunol. 73:912–920.

Penders, J., Stobberingh, E. E., Thijs, C., Adams, H., Vink, C., van Ree, R.

and van den Brandt, P. A. (2006). Molecular ﬁnger printing of the intestinal

microbiota of infants in whom atopic eczema was or was not developing.

Clin. Exp. Allergy 36:1602–1608.

Peral, M. C., Martinez, M. A. and Valdez, J. C. (2009a). Bacteriotherapy with

Lactobacillus plantarum in burns. Int. Wound J. 6:73–81.

Peral, M. C., Rachid, M. M., Gobbato, N. M., Martinez, M. A. H. and Valdez, J.

C. (2009b). Interleukin-8 production by polymorphonuclear leukocytes from

patients with chronic infected leg ulcers treated with Lactobacillus plantarum.

Clin. Microbiol. Infect. 16:281–286.

Peran, L., Camuesco, D., Comalada, M., Nieto, A., Concha, A., Adrio, J. L.,

Olivares, M., Xaus, J. Z. A. and Galvez, J. (2006). Lactobacillus fermentum,

a probiotic capable to release glutathione, prevents colonic inﬂammation in

the TNBS model of rat colitis. Int. J. Colorectal Dis. 21:737–746.

Pike, M. G., Heddle, R. J., Boulton, P., Turner, M. W. and Atherton, D. J. (1986).

Increased intestinal permeability in atopic dermatitis. J. Invest. Dermatol.

110:101–104.

Pillai, S., Oresajo, C. and Hayward, J. (2005). Ultraviolet radiation and skin

aging: Role of reactive oxygen species, inﬂammation and protease activa-

tion, and strategies for prevention of inﬂammation induced: A review. Int. J.

Cosmet. Sci. 27:17–34.

Pohjavuori, E., Viljanen, M. and Korpela, R. (2004). Lactobacillus GG effect

in increasing IFN-gamma production in infants with cow’s milk allergy. J.

Allergy Clin. Immunol. 114:131–136.

Prescott, S. and Bjorksten, B. (2007). Probiotics for the prevention or treatment

of allergic diseases. J. Allergy Clin. Immunol. 120:255–262.

Prescott, S. L., Dunstan, J. A. and Hale, J. (2005). Clinical effects of probiotics

are associated with increased interferon-gamma responses in very young

children with atopic dermatitis. Clin. Exp. Allergy 35:1557–1564.

Pucci, N., Novembre, E., Cammarata, M. G., Bernardini, R., Monaco, M. G.,

Calogero, C. and Vierucci, A. (2005). Scoring atopic dermatitis in infants

and young children: Distinctive features of the SCORAD index. Allergy

60:113–116.

Puch, F., Samson-Villeger, S., Guyonnet, D., Blachon, J. L., Rawlings, A. V. and

Lassel, T. (2008). The consumption of functional fermented milk containing

borage oil, green tea and vitamin E enhances skin barrier function. Exp.

Dermatol. 7:668–674.

Quadros, E., Landzert, N. M., Leroy, S., Gasparini, F. and Worosila, G. (1994).

Colonic absorption of insulin-like growth factor I in vitro. Pharm. Res.

11:226–230.

Rautava, S., Kalliom¨

aki, M. and Isolauri, E. (2002). Probiotics during pregnancy

and breast-feeding might confer immunomodulatory protection against atopic

disease in the infant. JACI, 109–121.

Rautava, S., Kalliomaki, M. and Isolauri, E. (2005). New therapeutic strategy for

combating the increasing burden of allergic disease: Probiotics-A nutrition,

allergy, mucosal immunology and intestinal microbiota (NAMI) research

group report. J. Allergy Clin. Immunol. 116:31–37.

Rijken, F., Kiekens, R. C. M. and Bruijnzeel, P. L. B. (2005). Skin-inﬁltrating

neutrophils following exposure to solar-simulated radiation could play an

important role in photoageing of human skin. Br. J. Dermatol. 152:321–328.

Ritti´

e, L. and Fisher, G. J. (2002). UV-light-induced signal cascades and skin

aging. Ageing Res. Rev. 1:705–720.

Roberfroid, M., Gibson, G. R., Hoyles, L., Mccartney, A. L., Rastall, R. and

Rowland, I. (2010). Prebiotic effects: Metabolic and health beneﬁts. Br. J.

Nutr. 104:S1–S63.

Rodriguez, K. L., Caputo, L. R. G., Carvalho, J. C. T., Evangelista, J. and

Schneedorf, J. M. (2005). Antimicrobial and healing activity of keﬁr and

keﬁran extract. Int. J. Antimicrobial. Agents. 25:404–408.

Romagnani, S. (1996). Thiand Th2 in human diseases. Clin. Immunol. Im-

munopathol. 80:225–235.

Rosen, L. D. and Breuner, C. C. (2007). Primary care from infancy to adoles-

cence. Pediatr. Clin. N. Am. 54:837–858.

Rosenfeldt, V., Benfeldt, E. and Nielsen, S. D. (2003). Effect of probiotic Lac-

tobacillus strains in children with atopic dermatitis. J. Allergy Clin. Immunol.

111:389–395.

Rosenfeldt, V., Benfeldt, E., Valerius, N. H., Pærregaard, A. and Michaelsen, K.

F. (2004). Effect of probiotics on gastrointestinal symptoms and small intesti-

nal permeability in children with atopic dermatitis. J. Pediatr. 145:612–616.

Salminen, S. J., Gueimonde, M. and Isolauri, E. (2005). Probiotics that modify

disease risk. J. Nutr. 135:1294–1298.

Sato, A., Hashiguchi, M., Toda,E., Iwasaki, A., Hachimura, S. and Kaminogawa,

S. (2003). CD11b+Peyer’s patch dendritic cells secrete IL-6 and induce IgA

secretion from naive B cells. J. Immunol. 171:3684–3690.

Schiffrin, E. J., Thomas, D. R., Kumar, V. B., Brown, C., Hager, C. and Van’t

Hof, M. A. (2007). Systemic inﬂammatory markers in older persons: The

effect of oral nutritional supplementation with prebiotics. J. Nutr. Health.

Aging 11:475–479.

Schmidt, W. P. (2004). Model of the epidemic of childhood atopy. Med. Sci.

Monit. 10:5–9.

Schultz-Larsen, F. H. J. (2002). Epidemiology of atopic dermatitis. Immunol.

Allergy Clin. North Am. 22:1–24.

Seifert, S. and Watzl, B. (2007). Inulin and oligofructose: Review of experimen-

tal data on immune modulation. J. Nutr. 137:2563–2567.

Shen, Q., Zhang, B., Xu, R., Wang, Y., Ding, X. and Li, P. (2010). Antioxi-

dant activity in vitro of the selenium-contained protein from the Se-enriched

Biﬁdobacterium animalis 01. Anaerobe 16:380–386.

Shida, K., Makino, K. and Morishita, A. (1998). Lactobacillus casei inhibits

antigeninduced IgE secretion through regulation of cytokine production in

murine splenocyte cultures. Int. Arch. Allergy Immunol. 115:278–287.

Sicherer, S. H. and Sampson, H. A. (1999). Food hypersensitivity and atopic

dermatitis: Pathophysiology, epidemiology, diagnosis, and management. J.

Allergy Clin. Immunol. 104:S114–S122.

Simmering, R. and Breves, R. (2009). Pre- and probiotic cosmetics. Hautarzt

60:809–814.

Sistek, D., Kelly, R., Wickens, K., Stanley,T., Fitzharris, P.and Crane, J. (2006).

Is the effect of probiotics on atopic dermatitis conﬁned to food sensitized

children? Clin. Exp. Allergy 36:629–633.

Smits, H. H., Engering, A. and van der Kleij, D. (2005). Selective pro-

biotic bacteria induce IL-10-producing regulatory T cells in vitro by

Downloaded by [University of Maine - Orono] at 03:58 25 April 2015

1240 M. R. ROUDSARI ET AL.

modulating dendritic cell function through dendritic cell-speciﬁc intercellu-

lar adhesion molecule 3-grabbing nonintegrin. J. Allergy Clin. Immunol. 115:

1260–1267.

Soter, N. A. (1990). Acute effects of ultraviolet radiation on the skin. Semin.

Dermatol. 9:11–15.

Sullivan, M., Schnittger, S. F., Mammone, T. and Goyarts, E. C. (2009). Skin

Treatment Method with Lactobacillus Extract. US Patent, US7510734B2.

Tannis, A. (2008). The Future of Probiotics: Superbugs, Asthma, Oral Health

and More. Wiley, Mississauga, Canada.

Tannock, G. W. (1995). Normal Microﬂora. An Introduction to Microbes In-

habiting the Human Body. Chapman & Hall, London, UK.

Taylor, A. L., Hale, J., Wiltschut, J., Lehmann, H., Dunstan, J. A. and Prescott,

S. L. (2006). Effects of probiotic supplementation for the ﬁrst 6 months of

life on allergen-and vaccine-speciﬁc immune responses. Clin. Exp. Allergy

36:1227–1235.

Taylor, A., Dunstan, J. and Prescott, S. (2007). Probiotic supplementation for

the ﬁrst 6 months of life fails to reduce the risk of atopic dermatitis and

increases the risk of allergen sensitization in high-risk children: A randomized

controlled trial. J. Allergy Clin. Immunol. 119:184–191.

Teodorescu, R. (1999). A Natural Eubiotic Product for Maintenance and Treat-

ment of Teguments. WIPO Patent, WO1999007332.

Trautmann, A., Akdis, M., Schmid-Grendelmeier, P., Disch, R., Br¨

oocker, E.

B., Blaser, K. and Akdis, C. A. (2001). Targeting keratinocyte apoptosis in

the treatment of atopic dermatitis and allergic contact dermatitis. J. Allergy

Clin. Immunol.108:839–846.

Vaarala, O. (2003). Immunological effects of probiotics with special reference

to lactobacilli. Clin. Exp. Allergy 33:1634–1640.

Vald´

ez, J. C., Peral, M. C., Rachid, M., Santana, M. and Perdig´

on, G. (2005).

Interference of Lactobacillus plantarum with Pseudomonas aeruginosa in

vitro and in infected burns: The potential use of probiotics in wound treatment.

Clin. Microbiol. Infect. 11:472–479.

van der Aa, L. B., Heymans, H. S., van Aalderen, W. M. and Al., E. (2010). The

Synbad Study Group. Effect of a new synbiotic mixture on atopic dermatitis

in infants: A randomized-controlled trial. Clin. Exp. Allergy 40:795–804.

Veckman, V., Miettinen, M., Pirhonen, J., Siren, J., Matikainen, S. and

Julkunen, I. (2004). Streptococcus pyogenes and Lactobacillus rhamnosus

differentially induce maturation and production of Th1-type cytokines and

chemokines in human monocyte-derived dendritic cells. J. Leukoc. Biol. 75:

764–771.

Viljanen, M., Savilahti, E. and Haahtela, T. (2005). Probiotics in the treatment

of atopic eczema/dermatitis syndrome in infants: A double-blind placebo-

controlled trial. Allergy 60:494–500.

Volkova, L. A., Khalif, I. L. and Kabanova, I. N. (2001). Impact of the impaired

intestinal microﬂora on the course of acne vulgaris. Klin. Med. 79:39–41.

von Hertzen, L. C., Savolainen, J., Hannuksela, M., Klaukka, T., Lauerma, A.,

M¨

akel¨

a, M. J., Pekkanen, J., Pietinalho, A., Vaarala, O., Valovirta, E., Varti-

ainen, E. and Haahtela, T. (2009). Scientiﬁc rationale for the ﬁnnish allergy

programme 2008–2018: Emphasis on prevention and endorsing tolerance.

Allergy 64:678–701.

Weston, S., Halbert, A. and Richmond, P. (2005). Effects of probiotics on atopic

dermatitis: A randomised controlled trial. Arch. Dis. Child. 90:892–897.

Wickens, K., Black, P. N., Stanley, T. V., Mitchell, E., Fitzharris, P., Tannock,

G. W., Purdie, G. and Crane, J. (2008). A differential effect of 2 probiotics

in the prevention of eczema and atopy: A double-blind, randomized, place-

bocontrolled trial. J. Allergy. Clin. Immunol. 122:788–794.

Winkler, P., Ghadimi, D., Schrezenmeir, J. and Kraehenbuhl, J. P. (2007).

Molecular and cellular basis of microﬂorahost interactions. J. Nutr. 137:

756S–772S.

Woods, G. M., Malley, R. C. and Muller, H. K. (2005). The skin immune

system and the challenge of tumour immunosurveillance. Eur. J. Dermatol.

15:63–69.

Xu, Y. and Fisher, G. J. (2005). Ultraviolet (UV) light irradiation induced signal

transduction in skin photoaging. J. Dermatol. Sci. 1:S1–S8.

Yamamoto, A., Takenouchi, K. and Ito, M. (1995). Impaired water barrier

function in acne vulgaris. Arch. Dermatol. Res. 287:214–218.

Yoshimura, A., Lien, E., Ingalls, R. R., Tuomanen, E., Dziarski, R. and Golen-

bock, D. (1999). Cutting edge: Recognition of gram-positive bacterial cell

wall components by the innate immune system occurs via Toll-like receptor

2. J. Immunol. 163:1–5.

Zeuthen, L., Christensen, H. R. and Frøkiær, H. (2005). Lactic acid bacte-

ria inducing a weak Interleukin-12 and Tumour Necrosis Factor Alpha re-

sponse in human dendritic cells inhibit strongly stimulating lactic acid bacteria

but act synergistically with gram negative bacteria. Clin. Vaccine Immunol.

13:365–375.

Zutavern, A., Brockow, I. and Schaaf, B. (2006). Timing of solid food in-

troduction in relation to atopic dermatitis and atopic sensitization: Results

from a prospective birth cohort study. LISA Study Group. Pediatrics 117:

401–411.

Downloaded by [University of Maine - Orono] at 03:58 25 April 2015

The Hygienic Significance of Microbiota and Probiotics for Human Wellbeing

Article

Full-text available

Dec 2024

The human body can be viewed as a combination of ecological niches inhabited by trillions of bacteria, viruses, fungi, and parasites, all united by the microbiota concept. Human health largely depends on the nature of these relationships and how they are built and maintained. However, personal hygiene practices have historically been focused on the wholesale elimination of pathogens and “hygiene-challenging microorganisms” without considering the collateral damage to beneficial and commensal species. The microbiota can vary significantly in terms of the qualitative and quantitative composition both between different people and within one person during life, and the influence of various environmental factors, including age, nutrition, bad habits, genetic factors, physical activity, medication, and hygienic practices, facilitates these changes. Disturbance of the microbiota is a predisposing factor for the development of diseases and also greatly influences the course and severity of potential complications. Therefore, studying the composition of the microbiota of the different body systems and its appropriate correction is an urgent problem in the modern world. The application of personal hygiene products or probiotics must not compromise health through disruption of the healthy microbiota. Where changes in the composition or metabolic functions of the microbiome may occur, they must be carefully evaluated to ensure that essential biological functions are unaffected. As such, the purpose of this review is to consider the microbiota of each of the “ecological niches” of the human body and highlight the importance of the microbiota in maintaining a healthy body as well as the possibility of its modulation through the use of probiotics for the prevention and treatment of certain human diseases.

NEUROCOSMETICS: AN EXTENSIVE OVERVIEW

Article

Full-text available

Mar 2025

The review on this fast-evolving field of neuro cosmetics, at the intersection of neuroscience and cosmetic science, has interestingly led to innovative skincare treatment approaches. The paper progresses from a basic discovery of neurogenic inflammation made by substance P in 1996 the more recent skin-brain axis of 2015 to its applications. The review focuses on neurotransmitters such as acetylcholine and serotonin, neuropeptides such as substance P and Calcitonin Gene-Related Peptide (CGRP), and the neuroendocrine cells, Merkel, and Langerhans cells, to achieve skin homeostasis, inflammation control, and aging. The article looks at neurocosmetic applications such as anti-aging, skin barrier enhancement, and pigmentation management to active ingredients such as acetyl hexapeptide-8, niacinamide, and cannabidiol. Also reviewed are delivery systems including nanoencapsulation, microneedle technology, and iontophoresis in enhancing bioavailability and penetration of neuroactive compounds. A meta-analysis of clinical trials is shown. One study, which lasted up to 24 w, registered a 27% decrease in wrinkles and an 18% increase in elasticity with the peptide complex; the second one described a 45% decrease in rosacea erythema with Alpha-Melanocyte Stimulating Hormone (α-MSH) and Transient Receptor Potential Vanilloid (TRPV1) antagonists. In this review, emerging areas for future research are AI-driven personalized neurocosmetics, interventions of the gut-brain-skin axis, chronocosmetics, epigenetic modulation, smart nanocarriers, and bioelectronic skin therapies. Safety and regulatory issues that arise are commented on, emphasizing long-term studies and standardized approaches. The review is apt for any researcher or dermatologist looking for a comprehensive overview of how neurocosmetics hold transformative promise in topical peptide formulations.

Evaluation of the Anti-Aging Properties of Ethanolic Extracts from Selected Plant Species and Propolis by Enzyme Inhibition Assays and 2D/3D Cell Culture Methods

Article

Full-text available

Mar 2025

Background: Skin aging is a complex biological process affected by internal and external factors that disrupt the skin structure, especially in sun-exposed areas. Elastin and collagen in the dermis layer, responsible for the skin’s resistance and elasticity, have been the main subject of research. Since tyrosinase (TYR) is an enzyme found in different organisms and plays an essential role in melanogenesis, inhibitors of this enzyme have been the target mechanism for skin-bleaching product research. Methods: We selected the plant species Cotinus coggygria Scop., Garcinia mangostana L., Pistacia vera L., Vitis vinifera L., and propolis, which exhibited activity against a minimum of three target enzymes—elastase, collagenase, and TYR—in our previous screening study to find the suitable raw material for a cosmetic product. In the current research, the extracts from these samples were tested through a cell-free enzyme assay using validated elastase, collagenase, and TYR inhibition kits. We also performed the safety and efficacy tests of the selected extracts with 2D/3D cell culture methods. Results: Our data revealed the propolis extract among the tested ones displayed remarkable anti-inflammatory activity in the 2D (NF-κB induction: 10.81%) and 3D assays. Cotinus coggygria leaf and Garcinia mangostana shell extracts exhibited anti-inflammatory activity in the 2D luciferase reporter assay via TNFα addition. C. coggygria leaf, V. vinifera (grape) seed, and propolis extracts were selected for testing in 3D cell culture methods based on the 2D cytotoxicity results with cell viability values of 54.75%, 93.19%, and 98.64% at 34.25 µg/mL, respectively. The general phytochemical profiles of these three extracts were examined in terms of 53 phenolic compounds with LC-MS/MS, revealing that quinic acid, epicatechin, and acacetin were the dominant phenolics among the tested ones. Conclusions: It is the first study conducted to evaluate the use of the extracts indicated above in cosmetics by employing procedures involving 3D cell culture.

Clinical Potential of Novel Microbial Therapeutic LP51 Based on Xerosis-Microbiome Index

Article

Full-text available

Dec 2024

Xerosis, characterized by dry, rough skin, causes discomfort and aesthetic concerns, necessitating effective treatment. Traditional treatments often show limited efficacy, prompting the need for innovative therapies. This study highlights the efficacy of microbiome therapeutic LP51, derived from a healthy vaginal microbiome, in improving xerosis. A double-blind clinical trial involving 43 subjects with dry inner arm skin compared the effects of a 2.9% LP51 extract formulation to a placebo over 4 weeks. The LP51 group exhibited a significant increase in stratum corneum hydration (10.0 A.U.) compared to the placebo group (4.8 A.U.) and a 21.4% decrease in transepidermal water loss (TEWL), whereas the placebo group showed no significant change. LP51 also demonstrated benefits in enhancing skin hydration, improving the skin barrier, and exhibited anti-atopic, anti-inflammatory, and antioxidant properties. Safety was confirmed through in vitro cytotoxicity tests. These effects are attributed to the microbiome-safe component in LP51 and its role in improving xerosis, reflected by an increase in the xerosis-microbiome index, defined by the Firmicutes/Actinobacteria ratio. These findings position microbiome therapeutic LP51 as a promising novel treatment for xerosis.

Tackling transmission of infectious diseases: A probiotic‐based system as a remedy for the spread of pathogenic and resistant microbes

Article

Full-text available

Jul 2024

Built environments (BEs) currently represent the areas in which human beings spend most of their life. Consistently, microbes populating BEs mostly derive from human occupants and can be easily transferred from BE to occupants. The hospital microbiome is a paradigmatic example, representing a reservoir for harmful pathogens that can be transmitted to susceptible patients, causing the healthcare‐associated infections (HAIs). Environmental cleaning is a crucial pillar in controlling BE pathogens and preventing related infections, and chemical disinfectants have been largely used so far towards this aim. However, despite their immediate effect, chemical‐based disinfection is unable to prevent recontamination, has a high environmental impact, and can select/increase antimicrobial resistance (AMR) in treated microbes. To overcome these limitations, probiotic‐based sanitation (PBS) strategies were recently proposed, built on the use of detergents added with selected probiotics able to displace surrounding pathogens by competitive exclusion. PBS was reported as an effective and low‐impact alternative to chemical disinfection, providing stable rebalance of the BE microbiome and significantly reducing pathogens and HAIs compared to disinfectants, without exacerbating AMR and pollution concerns. This minireview summarizes the most significant results obtained by applying PBS in sanitary and non‐sanitary settings, which overall suggest that PBS may effectively tackle the infectious risk meanwhile preventing the further spread of pathogenic and resistant microbes.

Progress in Probiotic Science: Prospects of Functional Probiotic-Based Foods and Beverages

Article

Full-text available

Apr 2025

Musaalbakri Abdul Manan

This comprehensive review explores the evolving role of probiotic-based foods and beverages, highlighting their potential as functional and “future foods” that could significantly enhance nutrition, health, and overall well-being. These products are gaining prominence for their benefits in gut health, immune support, and holistic wellness. However, their future success depends on addressing critical safety concerns and navigating administrative complexities. Ensuring that these products “do more good than harm” involves rigorous evaluations of probiotic strains, particularly those sourced from the human gastrointestinal tract. Lactic acid bacteria (LABs) serve as versatile and effective functional starter cultures for the development of probiotic foods and beverages. The review emphasizes the role of LABs as functional starter cultures and the development of precision probiotics in advancing these products. Establishing standardized guidelines and transparent practices is essential, requiring collaboration among regulatory bodies, industry stakeholders, and the scientific community. The review underscores the importance of innovation in developing “friendly bacteria,” “super probiotics,” precision fermentation, and effective safety assessments. The prospects of functional probiotic-based foods and beverages rely on refining these elements and adapting to emerging scientific advancements. Ultimately, empowering consumers with accurate information, fostering innovation, and maintaining stringent safety standards will shape the future of these products as trusted and beneficial components of a health-conscious society. Probiotic-based foods and beverages, often infused with LABs, a “friendly bacteria,” are emerging as “super probiotics” and “future foods” designed to “do more good than harm” for overall health.

Preclinical Safety Assessment of the Oral Administration of Lactobacillus plantarum GUANKE in Animal Models

Article

Full-text available

Mar 2025

Probiotics have a long history as fermented food or food supplements. The health benefits and safety profiles of probiotics are strain-specific and should be evaluated individually. The aim of this study was to assess the safety of the Lactobacillus plantarum GUANKE (GUANKE) strain by conducting pharmacological studies, oral toxicity assessments, and investigating the colonization and translocation of GUANKE in experimental animal models. Three pharmacological studies were conducted to examine the effects of oral administration of GUANKE on gastric emptying, bile secretion, and gastric juice secretion. In an acute toxicity study, rats were orally administrated with different doses of GUANKE and monitored for 14 days. In the subacute toxicity study, both rats and beagles were administrated with varying doses of GUANKE for 28 consecutive days to evaluate hematologic, biochemical, and histological effects. The results showed that GUANKE administration did not result in any adverse effect on hematological parameters, biochemical parameters, urinary parameters, and organ indices. Importantly, no translocation of GUANKE to extra-intestinal organs or blood was observed following administration of the CFDA-SE labeled strain. In summary, this study demonstrated the safety of GUANKE intake, which encourages its potential application as a probiotic in clinical trials.

Gut–X axis

Article

Full-text available

Feb 2025

Recent advances in understanding the modulatory functions of gut and gut microbiota on human diseases facilitated our focused attention on the contribution of the gut to the pathophysiological alterations of many extraintestinal organs, including the liver, heart, brain, lungs, kidneys, bone, skin, reproductive, and endocrine systems. In this review, we applied the “gut–X axis” concept to describe the linkages between the gut and other organs and discussed the latest findings related to the “gut–X axis,” including the underlying modulatory mechanisms and potential clinical intervention strategies.

Applications of Synbiotics as Cosmeceuticals

Chapter

Mar 2024

The Role of Probiotics in Skin Care: Advances, Challenges, and Future Needs

Article

Full-text available

Jul 2024

The skin, being the largest organ in the human body, plays a pivotal role in safeguarding the body against invasive pathogens. Therefore, it is essential to reinforce and protect this vital organ. Current research supports the impact of probiotics on skin health and their ability to alleviate various skin disorders. However, the effectiveness and probable side effects of probiotics in skin care remain a subject of debate, necessitating further investigation and analysis. Hence, this study aims to highlight existing gaps and future needs in the current research on probiotics in skin care and pave the way for future investigations. Therefore, we scrutinized the effects of oral (fermented foods and dietary supplements) and non-oral/topical probiotics on skin care, and the mechanism of probiotics that affect skin health. The results of most studies showed that fermented foods containing probiotics, particularly dairy products, positively impact skin health. The research results regarding the efficacy of probiotic supplements and live strains in treating skin disorders show promising potential. However, safety evaluations are crucial, to identify any potential adverse effects. While research has identified numerous potential mechanisms by which probiotics may influence skin health, a complete understanding of their precise mode of action remains elusive. However, it seems that probiotics can exert their positive effects through the gut-skin and gut-skin-brain axis on the human body. Therefore, following the identification of safe probiotics, additional studies should be carried out to establish optimal dosages, potential side effects, suitable regulatory guidelines, and validation methods.

Probiotics in Aging Skin

Chapter

Full-text available

Sep 2017

Health benefits of probiotics have been established recently and the scientific literature shows that the clinical uses of probiotics are broad and are open to continuing evaluation. The most common microorganisms used as probiotics are strains of lactic acid bacteria (LAB) including Lactobacilli and Bifidobacteria, which are part of the intestinal microbiota. Most probiotics are included in foods or dietary supplements and are aimed at functioning in the intestine. However, even if gastrointestinal tract has been the primary target, it is becoming evident that other conditions not initially associated with the gut microbiota might also be affected by probiotics.

US 8377679: Use of probiotic lactic acid bacteria for balancing the skin's immune system

Patent

Full-text available

Feb 2013

The present invention pertains to the use of probiotics for the preparation of a carrier for balancing the skin's immune function. In particular, the present invention pertains to the use of probiotic micro-organisms for balancing the skin's immune function under stress conditions, such as a exposure to ultraviolet radiation, specifically for enhancing the skin's immune activity and reducing the tendency to develop allergic reactions under such conditions.

A combination of Lactobacillus paracasei CNCM I-2116 and Bifidobacterium lactis CNCM I-3446 probiotic strains decreases skin reactivity

Conference Paper

Full-text available

Oct 2007

Lactobacillus fermentum ME-3 - an antimicrobial and antioxidative probiotic

Article

Mar 2009
Microb Ecol Health Dis

Interactions between commensal intestinal bacteria and the immune system

Article

Jan 2004

Although we might shudder at the thought of billions of bacteria living in our lower intestine, we are colonized by these passengers shortly after birth. However, the relationship is mostly of mutual benefit, and they shape our immune system throughout life. Here, we describe our developing understanding of the far-reaching effects that the commensal flora have on mucosal and systemic immunity and their relevance to the effects of hygiene on human disease.

Normal Microflora: an introduction to microbes inhabiting the human body

Article

Jan 1994

Gerald W Tannock

Probiotics prevent IgE-associated allergy until age 5 in cesarean-delivered children but not in the total cohort

Conference Paper

Jan 2009

Middleton's Allergy: Principles and Practice: Eighth Edition

Article

Jan 2013

Boasting a worldwide reputation as the leading text in allergy and immunology, Middletons Allergy continues its steadfast tradition of providing comprehensive coverage of state-of-the-art basic science, as well as authoritative guidance on the clinical concepts of day-to-day diagnosis and management of allergic disorders. Offering timely information that's suited for clinicians and researchers alike, Middleton's is a user-friendly and versatile source for the knowledge you need to provide optimal care to your patients!. "A valuable source of reference and pre-sifted information ...the editors are to be commending in keeping the book up-to-date and clinically valuable." Reviewed by: Imnunology News Date: March 2015.

A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age

Article

Jan 2007
Year Bk Dermatol Dermatol Surg

S. Raimer

Probiotics during the first 7 years of life: A cumulative reduction of eczema in a randomized, placebo-controlled trial

Article

Jan 2007
J ALLERGY CLIN IMMUN

Health Effects of Probiotics on the Skin

Abstract and Figures

Recommended publications

Probiotic For Skin Care

Effect of a New Synbiotic Mixture on Atopic Dermatitis in Children: a Randomized-Controlled Trial

PROBIÓTICOS NO TRATAMENTO DE DERMATITE ATÓPICA E ACNE

The Impact of Inoculation Rate and Order on Physicochemical, Microstructural and Sensory Attributes...

Future perspective of probiotics in dermatology: An old wine in new bottle