Health Effects of Probiotics on the Skin

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DOI: 10.1080/10408398.2012.680078 · Source: PubMed
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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.
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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
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Critical Reviews in Food Science and Nutrition, 55:1219–1240 (2015)
Copyright C
Taylor and Francis Group, LLC
ISSN: 1040-8398 / 1549-7852 online
DOI: 10.1080/10408398.2012.680078
Health Effects of Probiotics
on the Skin
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
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.
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
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).
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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-
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
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.,
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
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´
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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
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
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Health consequences of
probiotics to the skin
Preventing and
improvement of
eczema and
atopic dermatitis
water loss and
stratum corneum
barrier function
Produce a
(vitamin B2)
adjuvant role
in acne
and anti-
influences on skin
inflammation, skin
homeostasis, hair
growth, and
peripheral tissue
responses to stress
Protect the skin
immune system
induced skin
skin freshness
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
Inhibition of allergen-
induced tumors
(changes in systemic
immune responses)
Immunomodulation of the
skin in numerous ways
(changes in systemic
immune responses)
application on
the skin
Barrier to harmful foreign
environmental factors that are in
contact with the skin (protective shield)
Inhibition of
harmful intestinal
Act as antioxidant agents
(protection against
oxidative stresses)
Figure 2 The main mechanisms involved in health benefits of probiotics to the skin.
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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¨
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
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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).
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).
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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
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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
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
(Kukkonen et al., 2007)
L. rhamnosus LC705
B. breve Bb99 DSM
P. freudenreichii ssp.
shermanii JS DSM
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
Cumulative incidence of eczema similar in probiotics
and placebo groups, Probiotics group had less
IgE-associated eczema during second year
(Abrahamsson et al.,
L. rhamnosus GG
31 infants aged 2.5–15.7
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,
L. rhamnosus GG ATCC
119 infants aged 1.4–11.5 m
(mean age 6.5 m)
4 wk Increase of IFN-γin those with IgE-associated
(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
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
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)
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L. rhamnosus LC705 5 ×109cfu
B. breve Bbi99 2 ×108cfu
P. freudenreichi ssp
shermani JS
L. fermentum VRI-033
53 children aged 6–18
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
53 children aged 1–55
5×109 No improvement over placebo (Folster-Holst et al.,
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
102 children aged 3–12
5×10912 weeks No significant improvement in AD among probioticand
placebo groups
uber et al., 2007)
L. rhamnosus GG ATCC
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
B. breve Bb99 DSM
P. freudenreichii spp.
Shermanii JS DSM
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
(Wickens et al., 2008)
B. animalis subsp. lactis
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
P. freudenreichii ssp.
shermanii JS DSM
2×109cfu twice
L. casei 40 infants and children
1×109cfu twice
8 wk Improvement of atopic dermatitis with the mixture of
the seven strains of probiotics and
(Farid et al., 2011)
L. rhamnosus
S. thermophilus
B. breve
(Continued on next page)
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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.,
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
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
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
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
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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.,
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
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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,
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
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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,
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
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
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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.,
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).
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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.
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¨
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¨
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.,
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).
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
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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).
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.
effects of
on the skin
mal water
loss (on the
Barrier to
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.
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
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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.
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
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–
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
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