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Probiotics in dermatological and cosmetic products – application and efficiency

January 2023
Macedonian Pharmaceutical Bulletin 68(1):9-26

DOI:10.33320/maced.pharm.bull.2022.68.01.002

Authors:

Edita Hyseni

Saints Cyril and Methodius University of Skopje

Marija Glavas Dodov

Saints Cyril and Methodius University of Skopje

The term “probiotics” has first been used in 1907 by Elie Metchnikoff. Since then, probiotics have been part of research not only in regards of digestive health, but also inflammatory diseases. Lately, there has been an increased interest of probiotic’s effects in skincare. The management of atopic dermatitis, acne, psoriasis, photo aging, skin cancer, intimate care, oral care, wound healing is getting harder each passing day, due to increased antibiotic resistance and other side effects of conventional therapy. Therefore, new ingredients have been investigated and probiotics have been proved to be effective in treating various skin conditions. This review aims to evaluate the scientific evidence on topical and oral probiotics, and to evaluate the efficacy of cosmetic and dermatological products containing probiotics. Many studies have shown that skin and gut microbiome alterations have an important role in skin health. Although this is a new topic in dermatology and cosmetology, there have been some promising results in lots of research studies that the use of probiotics in cosmetic products may help improve the patient’s outcome. While oral probiotics have been shown to promote gut health, which influences the host immune system and helps treat different skin diseases, the mechanism of action of topical probiotics is not yet fully understood. Although the number of commercial probiotic cosmetic products released in the market is increasing and most of the studies have not shown any serious side effect of probiotics, further studies, in larger and heterogeneous groups are needed.

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* magl@ff.ukim.edu.mk

Macedonian pharmaceutical bulletin, 68 (1) 9 - 26 (2022)

ISSN: 1857-8969

UDC: 665.584 615.262

DOI: 10.33320/maced.pharm.bull.2022.68.01.002

Review paper

Probiotics in dermatological and cosmetic products –

application and efficiency

Edita Hyseni and Marija Glavas Dodov*

Center of Pharmaceutical nanotechnology, Faculty of Pharmacy,

Ss Cyril and Methodius University in Skopje, Majka Tereza 47, 1000 Skopje, N. Macedonia

Received: September 2022; Accepted: November 2022; Published: 25th January 2023

Abstract

The term “probiotics” has first been used in 1907 by Elie Metchnikoff. Since then, probiotics have been part of research not only in

regards of digestive health, but also inflammatory diseases. Lately, there has been an increased interest of probiotic’s effects in skincare.

The management of atopic dermatitis, acne, psoriasis, photo aging, skin cancer, intimate care, oral care, wound healing is getting harder

each passing day, due to increased antibiotic resistance and other side effects of conventional therapy. Therefore, new ingredients have

been investigated and probiotics have been proved to be effective in treating various skin conditions.

This review aims to evaluate the scientific evidence on topical and oral probiotics, and to evaluate the efficacy of cosmetic and

dermatological products containing probiotics. Many studies have shown that skin and gut microbiome alterations have an important role

in skin health. Although this is a new topic in dermatology and cosmetology, there have been some promising results in lots of research

studies that the use of probiotics in cosmetic products may help improve the patient’s outcome. While oral probiotics have been shown to

promote gut health, which influences the host immune system and helps treat different skin diseases, the mechanism of action of topical

probiotics is not yet fully understood. Although the number of commercial probiotic cosmetic products released in the market is increasing

and most of the studies have not shown any serious side effect of probiotics, further studies, in larger and heterogeneous groups are needed.

Keywords: probiotics, acne, atopic dermatitis, photoaging, psoriasis, immune system, wound healing, oral care, intimate care, skin

microbiome

Introduction

The integumentary system is formed by the skin and

its derivative structures. The skin is composed of three

layers: the epidermis, the dermis, and subcutaneous tissue

(Kanitakis, 2002). The outermost level, the epidermis,

consists of a specific constellation of cells known as

keratinocytes, which function to synthesize keratin, a long,

threadlike protein with a protective role. The middle layer,

the dermis, is fundamentally made up of the fibrillar

structural protein known as collagen. The dermis lies on the

subcutaneous tissue, or panniculus, which contains small

lobes of fat cells known as lipocytes. The thickness of these

layers varies considerably, depending on the geographic

location on the anatomy of the body. The eyelid, for

example, has the thinnest layer of the epidermis, measuring

less than 0.1 mm, whereas the palms and soles of the feet

have the thickest epidermal layer, measuring

approximately 1.5 mm. The dermis is thickest on the back,

where it is 30-40 times as thick as the overlying epidermis

(James et al., 2006).

Skin is the largest organ of the human body whose

primary functions consist of thermoregulation, immune

response, a physical barrier that protects from exogenous

factors. It is colonized by a diverse and large number of

E. Hyseni, M. Glavas Dodov

Maced. pharm. bull., 68 (1) 9 – 26 (2022)

microorganisms. Some of them are commensal and some

are transient. Most of them are beneficial to the host in

normal conditions, but some of them may be pathogenic.

So far, only about 200 microorganisms has been

characterized as pathogenic. The rest are either commensal

or facultative pathogenic. Due to differences in the

environment in different anatomic sites, the abundance of

bacteria is also different. Moist areas harbor mostly

Staphylococcus and Corynebacteria species. Sebaceous

sites host lipophilic species such as Propionibacterium. Dry

areas host predominantly Staphylococcus,

Propionibacterium, Micrococcus, Corynebacterium,

Enhydrobacter and Streptococcus species.

Understanding the skin’s microbiome is crucial to

gain insight about the benefits and/or skin diseases caused

by its alterations. Culture based methods have been widely

used in the identification of skin bacteria. However, some

bacteria require fastidious growth conditions and are

difficult to isolate. The development of molecular

techniques to identify and quantify microbial organisms has

enhanced our understanding of the skin bacterial diversity.

Genomic approaches to characterize skin bacteria rely on

sequence analysis of the 16S ribosomal RNA genes, which

is present in all bacteria and archaea, but not in eukaryotes.

The 16S rRNA gene contains variable regions, enabling

taxonomic classification and conserved regions, serving as

binding sites for PCR primers. Moreover, an organism does

not need to be cultured to determine its type by 16S rRNA

sequencing (Dethlefsen et al., 2007; Turnbaugh et al.,

2007). The disadvantage of this method is that it cannot

distinguish between methicillin-resistant and methicillin-

sensitive Staphylococcus spp. isolates.

Beside metagenomic analysis, metabolomic

identification, through mass spectrometry of metabolites,

lipids and peptides; bioinformatic software for analysis of

phylogenetics, metaproteomics and metabolomics; and

artificial intelligence-based data management and

prediction of microbial interactions (i.e. artificially created

microbial ecosystems [ACMEs]) are now being used in

combination for the quantification and profiling of

microorganisms, and their genetic material, environmental

conditions, and interrelations.

Skin microbiome

The microbiota refers to any microorganism present

in and on the body, such as gut, nose, oral mucosa,

pulmonary mucosa, scalp and the skin. The skin

microbiome is the genome of the microorganisms present

on the skin to which microorganisms maintain a complex

relationship.

The early age development of skin microbiome plays

a pivotal role in the establishment of the cutaneous

homeostasis and skin immune functions. Because of the

environmental changes, from mostly sterile environment in

the womb to a gaseous one with constant microbial

interaction, the first days after birth mark significant

changes in skin barrier composition and function. These

changes include reduction in transepidermal water loss,

skin pH and sebaceous activity and increase in water

content. The early colonization is dominated by

Staphylococci, but it decreases by the end of the first year

of life, contributing to an evenness of population. The

predominant species of infant skin are Firmicutes, followed

in decreasing order by Actinobacteria, Proteobacteria and

Bacteriodetes.

The skin region specific bacteria predominance

depends on a lot of factors such as: moisture levels, sebum

content, temperature, pH and UV exposure. It is also

influenced by the place of residence, either urban or rural.

Alterations in skin microbiome caused by intrinsic

and extrinsic factors is called dysbiosis. Dysbiosis does not

only occur between bacteria, but also between bacteria and

other skin commensals, such as bacteria and fungi. A

disequilibrium between bacteria and fungi strains on the

scalp, has been observed in subjects prone to dandruff.

Host skin cells continuously sample microorganisms

that reside in the epidermis and dermis through pattern

recognition receptors (PRRs). Part of the activated immune

system and how changes are regulated, distinguish a

commensal organism from a potential pathogen. Functions

of the skin microbiota in health and disease.

Probiotics in skin homeostasis

The term probiotic has been defined as “living

microorganisms which, when consumed in adequate

amounts, confer a health effect on the host” (World Health

Organization and Food and Agriculture Organization of the

United Nations, 2001). Lactobacillus and Bifidobacterium

have emerged as two of the most commonly used probiotics

(Ouwehand et al., 2002), although newer strains such as

Bacillus coagulans are being investigated with positive

results (Benson et al., 2012). Most commonly formulated

as fermentation products, probiotics counter pathogenic

bacteria, support barrier function, and contribute to the

regulation of the innate and adaptive immune responses

(Hacini-Rachinel et al., 2009). Probiotics can now be found

in household items ranging from yogurt to children’s

popsicles to facial cream. In Table 1, the role of probiotics

in dermatology as well as in cosmetology is presented.

Table 1. Potential probiotics role in dermatology and

cosmetology

Probiotics role in dermatology and cosmetic products

Acne treatment

Di Marzio et al. (2008)

Photo aging

Satoh et al. (2015)

Atopic dermatitis

Huang et al. (2017)

Immune regulation

Savan et al. (2006)

Wound healing

Peral et al. (2009)

Probiotics in dermatological and cosmetic products – application and efficiency

Макед. фарм. билт., 68 (1) 9 – 26 (2022)

Another example of potential use of probiotics for skin

health is Lactobacillus pes-odoris, which specifically

inhibits the odor-producing bacteria of the feet and

Lactobacillus ala-odoris, which prevents the formation of

odor in armpits. Both Lactobacilli cultures can improve the

effectiveness of deodorants, foot sprays, or lotions.

Additionally, probiotics can result in significant

benefits in protecting and restoring the skin barrier. In

patients with acne and rosacea, living microorganisms on

the skin are recognized as foreign by the body’s immune

system. The immune system springs into action to counter

this potential threat resulting in the inflammation, redness,

or bumps common in these skin conditions. Probiotics

applied topically sit on the skin’s surface and prevent the

skin cells from seeing the bad bacteria and parasites that

can cause this immune system response. This is known as

“bacterial interference,” as probiotics could protect the skin

and interfere with the ability of the bacteria and/or parasites

to provoke an immune reaction (Bowe, 2013; Sánchez-

Pellicer et al., 2022).

When certain types of probiotics are placed in contact

with skin cells, they calm the parts of the cells that may

want to react to the presence of pathogenic bacteria that

they see as a threat. These healthy signals produced by the

probiotics stop the skin cells from sending “attack”

messages to the immune system that result in flares of acne

or rosacea (Yan and Polk, 2011).

Mechanism of action of probiotics

The mechanisms whereby probiotics may play a role

in skin physiology are not fully elucidated. However, it is

proposed that, as shown for other commensal bacteria,

probiotics could be directly sampled in the lumen by

mucosal dendritic cells, which express tight junction

proteins and penetrate the gut epithelial monolayer (Uhlig

and Powrie, 2003). It is postulated that upon interaction of

the probiotic bacteria (or their components) with the

intestinal epithelium and/or direct interaction with

dendritic cells, other immune cells, such as Band T

lymphocytes may be activated (primed) and immune

mediators, including cytokines, may subsequently be

released. These cytokines, bacterial fractions, and primed

immune cells may be transported via the blood to other

organs, including the skin, where they could modulate the

immune status.

In addition, the improvement of reactive skin after

probiotic supplementation could also result from a direct

activity of the ingredient on neurosensitive mechanisms.

On the one hand, immune-regulating properties of

probiotics at the skin level could modulate the

inflammatory reactions generated by the release of

neuromediators involved in skin neurosensitivity

(Nickoloff and Naidu, 1994; Ohta et al., 2000; Thurin and

Baumann, 2003). On the other hand, the capacity of certain

probiotics to modulate the production of regulating

cytokines and growth factors (as Transforming growth

factor beta) may play a role in the proliferation and

differentiation of skin keratinocytes, which are important

for skin barrier repair (Von der Wied et al., 2001). Such

possible effects on the process of generating the stratum

corneum allow the quality of the cutaneous barrier function

and skin dryness to be improved (Thurin and Baumann,

2003).

Probiotics in dermatotherapy and cosmetology

Acne treatment

Acne is a chronic inflammatory disease that is caused

by hyperproliferation of Propionibacterium acnes in hair

follicles, hyperkeratinisation and sebum overproduction.

Beside androgen levels and pathogenic influence, the

alterations in the skin microbiome play an important role

in the presence and severity of acne. It is one of the 10 most

prevalent disorders in the world and has severe adverse

effects on the quality of the life in patients.

The co-morbidity of chronic skin conditions and

mental health disorders has long been recognized, and in

recent years’ specialty psychodermatology and

neurodermatology groups have emerged. Acne vulgaris is

a common dermatological disorder frequently associated

with depression, anxiety and other psychological sequelae.

The mental health impairment scores among acne patients

are higher vs. a number of other chronic, non-psychiatric

medical conditions, including epilepsy and diabetes. Along

with the psychological fallout, there have also been

indications that acne patients are at a higher risk for

gastrointestinal distress. For example, one study involving

over 13,000 adolescents showed that those with acne were

more likely to experience gastrointestinal symptoms such

as constipation, halitosis, and gastric reflux. In particular,

abdominal bloating was 37% more likely to be associated

with acne and other seborrheic diseases.

Stokes and Pillsbury made numerous references to the

use of L. acidophilus and L. acidophilus-fermented milk

products as a treatment modality in the context of the brain-

gut-skin inflammatory process. Indeed, other physicians

writing in the 1930s made reference to the popularity of L.

acidophilus cultures among the general public as an

internal means to treat acne. However, despite the apparent

appeal of what would later be described as probiotics, there

was little research to determine efficacy. The first formal

clinical case report series on the potential value of

Lactobacillus probiotics was published in 1961. A

physician from Union Memorial Hospital in Baltimore,

Robert H. Siver, followed 300 patients who were

administered a commercially available probiotic (Laxtinex

tablets providing a mixture of L. acidophilus and L.

bulgaricus). He used a protocol of probiotic

supplementation for 8 days followed by two-week wash

out then re-introduction for an additional eight days. The

rationale for such a dosing regimen is unclear. In any case,

he reported that 80 percent of those with acne had some

degree of clinical improvement, and that the intervention

E. Hyseni, M. Glavas Dodov

Maced. pharm. bull., 68 (1) 9 – 26 (2022)

was most valuable in cases of inflammatory acne. Without

a placebo control, Dr Siver concluded merely that ‘interactions of skin manifestations of acne vulgaris and of

metabolic processes of the intestinal tract are suggestive’.

Table 2. Beneficial properties and application of some probiotics in dermatology and cosmetology

Probiotic

Benefit

References

Streptococcus thermophilus

Increases ceramide production

Di Marzio et al. (1999)

Enterococcus faecalis

Reduces inflammatory lesions

Kanget a l. (2009)

Streptococcus salivarius

Immune modulator

Cosseau et al (2008)

Bifidobacterium longum

Skin inflammation

Guéniche et al. (2010)

Lactobacillus paracasei

Skin inflammation

Guéniche et al. (2010)

Lactobacillus johnsonii

UV protection

Bouilly-Gauthier et al. (2010)

Lactobacillus plantarum HY7714

Anti photoaging effect

Lee et al. (2015)

Lactobacillus acidophilus IDCC 3302

tyndallizate

UVB protection

Smith, (1996)

Lactobacillus buchneri

Photoprotection

Kang et al. (2020)

Nitrosomonas eutropha

Anti-wrinkles

Notay et al. (2019)

Lactobacillus fermentum

SCORAD reduction

Huang et al. (2017)

Lactobacillus plantarum CJLP133

Prevention of AD symptoms

Han et al. (2012)

Bifidobacterium lactis UABLA-12

AD improvement

Gerasimov et al. (2010)

Vitreoscilla filiformis lysate

Improves AD symptoms

Gueniche et al. (2008)

Bifidobacterium dentium

Reduces the incidence of AD

Avershina et al. (2017)

Pseudomonas aeruginosa

Wound healing

Valdéz et al. (2005)

Streptococcus thermophilus

Acne treatment

Di Marzio et al. (2008)

Enterococcus faecalis SL-5

Acne treatment

Kang et al. (2009)

Bifidobacterium longum

Acne treatment

Guéniche, A et al. (2010)

Lactobacillus paracasei

Acne treatment

Wang and Wang, (2015)

Lactobacillus johnsonii

Photoaging

Bouilly-Gauthier et al., (2010)

Lactobacillus plantarum HY7714

Photoaging

Lee et al., (2015)

Lactobacillus acidophilus IDCC 3302

tyndallizate

Photoaging

Smith WP, (1996)

Lactobacillus buchneri

Photoaging

Kang YM et al., (2020)

Nitrosomonas eutropha

Photoaging

Notay et al. (2019)

Lactobacillus fermentum

Atopic dermatitis

Huang et al. (2017)

Lactobacillus salivarius

Atopic dermatitis

Huang et al. (2017)

Lactobacillus plantarum CJLP133

Atopic dermatitis

Han et al., (2012)

Lactobacillus rhamnosus

Atopic dermatitis

Kalliomaki et al. (2001)

Lactobacillus paracasei

Atopic dermatitis

Wang and Wang, (2015)

Lactobacillus fermentum

Atopic dermatitis

Wang and Wang, (2015)

Bifidobacteria lactis

Atopic dermatitis

Sistek et al. (2006)

Lactobacillus sakei

Atopic dermatitis

Woo et al. (2010)

Vitreoscilla filiformis lysate

Atopic dermatitis

Gueniche et al., (2008)

Propionibacterium freudenreichii

Atopic dermatitis

Sikorska and Smoragiewicz (2013)

Lactococcus lactis

Atopic dermatitis

Sikorska and Smoragiewicz (2013)

Lactobacillus bulgaricus

Atopic dermatitis

Sikorska and Smoragiewicz (2013)

Bifidobacterium dentium

Atopic dermatitis

Avershina e. et al., (2017)

Bifidobacterium lactis HN019

Atopic dermatitis

Wickens K. et al, 2018

Lactobacillus casei CRL 431

Immune regulation

Galdeano et al. (2006)

Lactobacillus paracasei CNCM I-1518

Immune regulation

Galdeano et al. (2006)

Lactobacillus plantarum

Wound healing

Peral et al. (2009)

Probiotics in dermatological and cosmetic products – application and efficiency

Макед. фарм. билт., 68 (1) 9 – 26 (2022)

The effectiveness of conventional acne treatment

including oral and topical antibiotics has been decreasing,

due to the increased antibiotic resistance. Another major

concern caused by antibiotics is the damage to stable skin

microbiome and the resistance of non-target bacteria. In

order to overcome these limits and find new ways to

improve the treatment outcome, it is recommended to avoid

the use of topical and oral antibiotics as monotherapy or

polytherapy and supports a combination of a topical

retinoid and antimicrobial, eg. Benzoyl peroxide, as the

first line therapy.

Recent studies have brought new insights in

understanding the pathophysiology of acne. It has been

found by metagenomic studies that the abundance of P.

acnes between healthy individuals and acne patients is

similar. Instead, the disbalance between phylotypes of P.

acnes appears to have a significant role in the triggering of

acne. The predominant P. acnes strain in acne patients was

found to be the phylotype IA1 (also known as the CC18

clonal complex or A1 SLST-type). Moreover, the virulence

of phylotypes IA1 and IB in acne is higher than in normal

skin. Finally, P. acnes types IA and IB were found to

induce greater levels of production of the human

antimicrobial peptide (AMP), β-defensin 2 (hBD2), from

cultured sebocytes, and displayed higher levels of lipase

activity than a type II isolate.

As for intestinal permeability in acne vulgaris, there

have been hints that the intestinal lining may be

compromised. One older study used a blood serum

complement fixation test and reported that acne patients

were more likely to show enhanced reactivity to bacterial

strains isolated from stool. Approximately 66% of the 57

patients with acne showed positive reactivity to stool

isolated coliforms, this compared to none of the control

patients without active skin disease. Furthermore, a study

involving 40 acne patients showed both the presence of,

and high reactivity to, lipopolysaccharide (LPS)

endotoxins in the blood as measured by the stellate fibrin

crystal test. None of the matched healthy controls reacted

to the E. coli lipopolysaccharide endotoxin (E. coli LPS),

while 65% of the acne patients did have a positive reaction.

The inference of these results is that circulating endotoxins

derived from gut microbes is not an uncommon feature of

acne vulgaris, and one indicating that intestinal

permeability is a potential issue for a sizable group of acne

patients.

The first report that ‘topical bacterio-therapy’ (via

local Lactobacillus bulgaricus application) may be helpful

in acne and seborrhea was published in 1912. However, it

was not until 1999 that proper scientific technique was used

to evaluate some of the potential skin-specific benefits of

lactic acid bacterial application. Specifically, researchers

showed that the lactic acid bacteria Streptococcus

thermophilus, a species found in most yogurts, can increase

ceramide production when applied to the skin for 7 days as

a cream. This work, which has since been replicated, is of

relevance to acne, particularly when considering that some

of the ceramide sphingolipids, most notably

phytosphingosine (PS), provide both antimicrobial activity

against Propionibacterium acnes (P. acnes) and direct

anti-inflammatory activity. Sphingolipids have been noted

to be low in acne, and the seasonal loss of ceramides may

be a driving force behind much higher dermatological

office visits for acne during winter months. Indeed, topical

application of 0.2% PS reduced papules and pustules by

89% in a recent 2-month pilot study. Additional studies

hinting at the value of topical probiotics in acne include

recent reports that strains of Bifidobacterium longum and

Lactobacillus paracasei can attenuate skin inflammation

mediated by substance P. This is of relevance because

substance P may be a primary mediator of stress-induced

amplification of inflammation and sebum production in

acne. Two separate reports have also indicated that various

probiotic lactic acid bacteria can provide in vitro

antimicrobial activity against P. acnes. The latter study

also used a clinical arm, the results showing that topical

application of an Enterococcus faecalis probiotic lotion for

8 weeks reduced inflammatory lesions by over 50% vs.

placebo. Certain substances secreted by bacterial strains,

such as antimicrobial peptides, have been shown to inhibit

growth of P. acnes. Streptococcus salivarius, a prominent

member of the oral microbiota of healthy humans, has been

shown to secrete a bacteriocin-like inhibitory substance

(BLIS-like substance) capable of inhibiting P. acnes. In

addition to the antimicrobial activity, S. salivarius bacterial

cells themselves inhibit a number of inflammatory

pathways, thus acting as immune modulators. Finally, the

application of select 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.

In healthy skin, P. acnes plays a beneficial role in the

cutaneous microbiota of the pilosebaceous unit. It limits

the growth of S. aureus, such as community-acquired

methicillin-resistant S. aureus, as well as that of S.

pyogenes in maintaining an acidic pH of the pilosebaceous

follicle by hydrolysing sebum triglycerides and by

secreting propionic acid.

However, during puberty, over-colonisation of the

pilosebaceous unit by P. acnes may lead to a loss of

diversification and dysbiosis, potentially causing acne. A

recent clinical study using the single-locus sequence typing

method investigated P. acnes subgroups on the face and

back in patients with severe acne and in healthy subjects.

In almost 75% of the acne patients, P. acnes phylotypes

were identical on the face and back, whereas this was only

the case in about 45% of the healthy subjects. In the healthy

group, phylotypes IA1 (39%) and II (43%) were the main

phylotypes, whereas in the acne group IA1 (84%),

especially on the back (96%), was the main phylotype. This

may confirm the hypothesis that acne severity may be

associated with a loss of diversity of P. acnes phylotypes,

E. Hyseni, M. Glavas Dodov

Maced. pharm. bull., 68 (1) 9 – 26 (2022)

following a selection of phylotype IA1/clonal complex

(CC) 18 present in all acne patients. Therefore, different

inflammatory profiles, depending on the phylotype (i.e.,

phylotype IA1, which has been mainly observed on the face

and back of acne patients and cluster of P. acnes activating

the innate immunity via the expression of protease-

activated receptors (PARs), tumor necrosis factor-α, and

the production of interferon-γ and interleukins [IL-8], have

been observed. Moreover, P. acnes activates the release of

lipases, matrix metalloproteinases, and hyaluronidases,

leading to hyperkeratinisation of the pilosebaceous unit and

finally to comedones, papules, and pustules.

The application of live bacteria on skin poses several

challenges. Postbiotic is a relatively new term used to

describe microbial metabolites. These include short-chain

fatty acids, extracellular metabolites, functional proteins,

cell lysates and other products derived from a probiotic that

can influence the microbiome composition. Postbiotics

have a long shelf life, safety and possess multiple health

benefits. They have been evaluated for anti-inflammatory,

immunomodulatory, anti-obesogenic, antihypertensive,

hypocholesterolemic, antiproliferative and antioxidant

benefits.

Various research groups have reported the presence of

bacteriocins in the Bacillus genus. LactoSporin is an

extracellular metabolite purified from Bacillus coagulans

MTCC 5856 fermented broth with an INCI name Bacillus

ferment filtrate extract. The potential mechanism of

LactoSporin as an antimicrobial agent is by pH drop,

microbial biofilms inhibition, and draining the ions from

the targeted cells.

A study suggests that LactoSporin is a postbiotic that

is thermostable and stable at an acidic pH. LactoSporin 2%

w/w cream was a safe antiacne formulation with efficacy

comparable to the standard treatment of benzoyl peroxide

2.5% gel. The onset of efficacy was very early for

LactoSporin as early as three days especially for closed

comedones, providing a quicker benefit than benzoyl

peroxide. The major finding of this study shows that

LactoSporin reduces the sebaceous secretion by its 5-alpha

reductase inhibitory and antimicrobial properties, which are

better than benzoyl peroxide and can be a potential

ingredient for other Seborrheic conditions as well.

Considering the clinical efficacy, continuous treatment and

patient satisfaction, LactoSporin is highly suitable for

treating subjects with mild-to-moderate acne vulgaris.

Further studies on a larger sample in multiple ethnic

populations may substantiate our findings.

Di Marzio et al. (2008) conducted an in vitro study

during which he added the bacterium Streptococcus

thermophilus to human keratinocyte cell cultures and found

an increase in the production of ceramides. He believed this

was due to S. thermophilus’ possession of

sphingomyelinase, an enzyme that hydrolyzes

sphingomyelin into ceramides. Many bacteria have been

reported to produce extracellular sphingomyelinase

including the genera Bacillus, Listeria, Staphylococcus,

Mycobacterium, Chlamydia, Pseudomonas, Leptospira,

and some species of Helicobacter. Although this enzyme

primarily functions as a virulence factor for the bacteria, its

ability to increase ceramide production may provide a

beneit in treating skin diseases. In the next phase of the

study, Di Marzio tested this theory in vivo on 17 healthy

subjects with normal skin. The subjects were instructed to

apply 0.5 g of a topical probiotic formulation consisting of

Streptococcus thermophilus twice a day to the volar surface

of one of their forearms. They applied the vehicle alone to

the contralateral forearm for comparison. An additional

four subjects were treated with sphingomyelinase purified

from Bacillus cereus to ensure that the results produced

were specific to the sphingomyelinase and not another

component within the bacterium. After seven consecutive

days of application, the probiotic formulation containing S.

thermophilus caused an increase in the production of

ceramides in the stratum corneum, which was comparable

to the results seen using the sphingomyelinase extracted

from B. cereus. These results demonstrated that the

sphingomyelinase produced by S. thermophilus may

improve skin barrier function.

Ceramides not only have a role in water permeability,

but they also play a part in the antimicrobial and anti-

inflammatory properties of the skin. The exact

antimicrobial mechanism of ceramides has not been

confirmed; however, there are many theories: reduction of

bacteria adherence to epithelial cells, inhibition of bacterial

protein kinases, and/or damage to the cell wall of the

bacteria. Aware of their antimicrobial properties, Pavicic et

al. performed a study in 2007 to evaluate the role of

ceramides in patients with acne. The study consisted of

both an in vitro and in vivo phase. In vitro, he found that

phytosphingosine (PS), one of the four types of sphingoid

bases that make up ceramides, inhibited growth of

Propionibacterium acnes, an important contributor to acne

formation. From these findings, he performed a two-part in

vivo pilot study testing a 0.2% PS formulation on subjects

with acne. In the first part, 30 subjects with acne applied a

topical medication containing PS with benzoyl peroxide

(PS-BPO) to half of their face versus benzoyl peroxide

(BPO) alone to the contralateral side of their face two times

per day. After 2 months, comedones were reduced by 72%

and inflammatory papules and pustules by 88% in the PS-

BPO group versus 22 and 32%, respectively, in BPO only

group. In another arm of the trial, 10 subjects applied PS

alone to half of their face and a placebo cream alone to the

other side of their face twice a day. After 2 months, the

placebo increased comedones by 43% compared to only

6% in the PS group. More significant results were seen in

inflammatory acne numbers with an 89% reduction

observed in the PS group compared to no change in the

placebo group.

A similar study in 2009 by Kang et al. demonstrated

the effects of the bacterium, Enterococcus faecalis SL-5 (a

very common inhabitant of the human gastrointestinal

tract) and its effect on P. acnes. He conducted in vitro and

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Макед. фарм. билт., 68 (1) 9 – 26 (2022)

in vivo studies. In the in vitro aspect of the study, E. faecalis

proved to be bacteriocidal to P. acnes due to a bacteriocidin

named ESL5. In the clinical trial, 70 subjects with mild-to-

moderate acne were enrolled in an 8-week double-blind,

randomized, placebo-controlled phase III study. Subjects

were randomized into the probiotic or placebo group.

Those in the experimental group applied a lotion

containing ESL5 to the areas of the face involved with acne

twice per day, and the control group applied a placebo

lotion twice daily. After 8 weeks of application, a decrease

in the number of comedones was seen in the probiotic

group compared to the placebo group; however, these

results were not statistically significant. In the

inflammatory lesion counts, a statistically significant

reduction of greater than 50% was observed in the E.

faecalis group compared to placebo.

Photoaging

Skin aging has intrinsic and extrinsic components.

Intrinsic aging is related to genetic factors and is a set of

physiologic processes related to the passage of time that

includes thinning of epidermal and dermal skin layers and

increasing dryness. The extrinsic skin-aging process is

characterized by coarse wrinkles, loss of elasticity,

epidermal thickening, dryness, laxity, rough appearance,

and pigmentation disorder.

Photoaging refers to premature aging of the skin due to

repeated light exposure. Its clinical manifestations,

histopathology, and biochemical changes are different

from the natural aging of skin. Photoaging reduces the

amount of mature type I collagen and elastic fibers in the

dermis of the skin. The clinical characteristics of

photoaging occur mainly on exposed skin, such as the face,

neck, and forearm, where rough skin, loss of elasticity,

deepening and thickening of wrinkles, a leather-like

appearance, pigmentation, and dilated capillaries can occur

(Qin et al., 2018). Studies have shown that approximately

65% of patients with melanoma and 90% of patients with

non-melanoma skin cancers, including BCC and SCC, are

associated with skin photoaging (Damiani and Ullrich,

2016). Many external factors are attributed to photoaging

of the skin, such as ultraviolet (UV), infrared, chemical

smog, dust, and smog, among which UV radiation is the

most significant (Markiewicz and Idowu, 2018).

The occurrence and development of skin photoaging

mediated by UV radiation involves multiple pathways,

including apoptosis, proliferation, autophagy, DNA repair,

checkpoint signal transduction, cell transduction, and

inflammation. UV radiation is generally categorized

according to wavelength into long-wave UVA (315–400

nm), medium-wave UVB (280–315 nm), and short-wave

UVC (200–280 nm). Although UVB radiation (280–315

nm) accounts for only 1–2% of the UV rays of the Sun, it

is considered to be the main environmental carcinogen that

causes skin cancer and is related to the occurrence and the

development of tumors (Panich et al., 2016; Gherardini et

al., 2019). Experimental models are the most widely used

photoaging models. This type of experimental model often

uses UVB because the skin tissue changes caused by UVB

are very similar to photoaging of human skin (Kim et al.,

2019b).

It has been reported that probiotic bacteria may be

highly effective in protecting the skin from photoaging, as

oral supplementation prior to UVB exposure was

demonstrated to prevent TEWL, increase epidermal

thickness, and alleviate damage to tight junction structures

and the basement membrane in a mouse model (Bouilly-

Gauthier et al., 2010; Satoh et al., 2015). The probiotic

gram-positive bacterium Lactobacillus acidophilus

inhabits the intestines and serves an important role in the

maintenance of gut health; however, it is not known

whether it can protect against photoaging induced by UV

radiation.

Recent clinical trials have shown protective effects of

dietary supplements containing Lactobacillus johnsonii

alone or combined with carotenoids against early UV-

induced skin via regulation of immune cells and

inflammatory cytokines (Bouilly-Gauthier et al., 2010).

Recent experiments in hairless mice have suggested

that in addition to regulating immune responses in the skin,

orally administered probiotics may exert anti-aging effects

by suppressing wrinkle formation and increasing skin

elasticity. Furthermore, our recent experiments in hairless

mice have shown that oral administration of L. plantarum

HY7714 (HY7714) exerts anti-photoaging effects through

reduction of wrinkle formation and suppression of

epidermal thickening and that skin hydration increases in

association with increasing ceramide level via regulation

of serine palmitoyltransferase and ceramidase expression

in the mice skin (Lee et al., 2015).

A study demonstrated the protective effect of L.

acidophilus IDCC 3302 tyndallizate on HaCaT

keratinocyte damage induced by UVB exposure.

Tyndallizate was analyzed for its nutrients including

carbohydrate, crude protein, crude fat, moisture, and ash

(Smith WP, 1996). For small molecule analysis, lactic acid

was detected as a major chemical component and it is

reported that topical lactic acid has cosmetic benefit

(LeBlanc et al., 2017). In previous studies beneficial

effects of short-chain fatty acids and vitamins produced by

probiotics have been reported (Preidis et al., 2011). In this

study Im et al. (2019), tyndallizate was hypothesized to be

helpful in skin rejuvenation. The detailed mechanisms

regarding anti-wrinkle activity require further study.

Sharma et al. (2016) explain that probiotics can restore

acidic skin pH, alleviate oxidative stress, attenuate

photoaging, improve skin barrier function, and enhance

hair quality.

Plant extracts fermented with Lactobacillus buchneri

(PELB), found in Kimchi, were evaluated regarding their

anti-photoaging effects. The authors investigated the anti-

photoaging effect of PELB in ultraviolet light (UVB)-

induced photoaging in in vitro models. They pre-treated

normal human dermal fibroblasts and epidermal

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keratinocytes with PELB and that had been exposed to

UVB. They found that PELB decreased elastase activity

and increased type I collagen expression in the UVB-

induced photoaging in vitro model, reduced collagenase

activity, and promoted the expression of moisture factor

and antioxidant enzymes. The study results show that the

PELB could be useful in the cosmetic industry due to its

protective effects against UVB-induced photoaging (Kang

et al., 2020).

Notay et al. (2019) investigated the use of topical

Nitrosomonas eutropha for cosmetic improvement of facial

wrinkles. They found a significant improvement in wrinkle

depth severity, hyperpigmentation of the forehead and

glabella in the group receiving high topical concentration

of the probiotic formula.

Atopic dermatitis

Atopic dermatitis is a chronic inflammatory disease

that affects 1 in 10 people in their lifetime. The etiology of

atopic dermatitis is very complex. It can be caused by

microbiome alterations, genetic factors, environmental

factors, immune dysregulation and is characterized by

scaly, pruritic, erythematous lesions.

AD is known to initiate with Th2, Th22 and Th17 cell

activation (acute phase), before chronicity, defined by the

onset of a Th1 cell response alongside the continued

activation of Th2 and Th22 cells. This mechanism could be

explained by the presence of a positive feedback loop made

by TSLP (thymic stromal lymphopoietin), IL-4 and IL-13.

TSLP, produced by keratinocytes, drives Th2 polarization

and activates dendritic cells, while IL-4 and IL-13 act on

keratinocytes to further increase TSLP level. Thymus and

activation-regulated chemokine (TARC) levels also

increase in the stratum corneum of skin lesions of AD

patients, which is correlated with disease severity,

especially with erythema, oedema/papules, and

oozing/crusts. These two cytokines have been used as

indicators of skins inflammation in AD lesions.

The conventional treatment strategy for AD includes

hydration with emollients, avoidance of individual trigger

factors, anti-inflammatory therapy with topical

corticosteroids or calcineurin inhibitors and treatment of

secondary infections. For severe AD treatment, a recent

antibody has been approved, Dupilumab, which is an

injectable human lgG4 monoclonal antibody that inhibits

IL-4 and IL-13 cytokine responses, and has provided

remarkable results. However, its use is still debated

regarding its suitability as a routine treatment. Although

anti-inflammatory drugs are considered as the first

pharmacological treatment, in recent years, concerns have

arisen due to the high incidence of side effects. In addition,

corticosteroids are not feasible for delicate parts of the

body, such as the eyelids, and are discouraged in childhood.

Increasing evidence shows that patients affected by AD

have a modified composition of the gut microbiome and

lack microbial diversity compared to healthy controls. This

bacterial dysbiosis may be considered a possible target for

the treatment and prevention of AD. Therefore, the

supplementation of the diet with probiotics, prebiotics and

postbiotics may have a role in the management of AD

because of their capacity of modulation of the microbiota.

Recent studies have shown that gut microbiomes have

been implied in the development and shaping of the host

immune system. Gut dysbiosis-alterations of microbial

diversity and abundance due to lifestyle and diet

correspond to the impaired inflammatory response to a

particular antigen. This phenomenon has been

demonstrated in patients with AD (Lee JH et al., 2016). In

general, it is known for its short-chain fatty acid- (SCFA-)

producing capability. Bifidobacterium, Propionibacterium,

Coprococcus, Blautia, and Eubacterium are significantly

reduced in patients with AD (Ellis et al., 2019; Zheng et al.,

2016). Since SCFA can induce regulatory T (Treg) cell

expansion, reduction of SCFA may result in a shift of Treg-

)17 balance towards )17, T helper cell known for its role in

orchestrating proinflammatory immune response.

Repopulating gut microbiota has been suggested to be an

alternative mechanism to treat various immunologic

diseases, including AD (Forbes et al., 2016). However, the

approach is still controversial (Williams et al., 2008).

An analysis of the gut microbiota of patients with AD

has shown an intraspecies compositional change in

Faecalibacterium prausnitziithat reduces the number of

high butyrate and propionate producers. Butyrate and

propionate are microbial-produced short-chain fatty acids

with an anti-inflammatory role. Moreover, butyrate has

been shown to be a key player in maintaining gut barrier

integrity. Therefore, reduced levels in the microbiota of

both butyrate and propionate producers may result in a pro-

inflammatory state in the gut and a loss of barrier integrity.

All these data indicate the potential role of probiotics as

microbiota recovery players, and consequently as potential

nutritional supplements in AD treatment.

Huang et al. (2017) included 13 randomized

controlled studies (1,070 total subjects) in a recent meta-

analysis. The data suggested an overall benefit of probiotics

supplementation in children with AD, indicated by a

reduction of the SCORAD values of −4.50 (95%

confidence interval=−7.45 to −1.54, p value < 0.001) in

children aged 1–18 years. The beneficial effect was

especially evident for Lactobacillus fermentum (mean

difference=−11.42, 95% confidence interval=−13.81 to

−9.04), Lactobacillus salivarius (mean difference=−7.21,

95% confidence interval=−9.63 to −4.78) and a mixture of

different strains (mean difference=−3.52, 95% confidence

interval=−5.61 to −1.44).

A randomized, double-blind, placebo-controlled

study investigated the effects of the use of the L. plantarum

CJLP133 strain in the prevention of AD symptoms. The

study was performed for a time period of 12 weeks among

children who were one and 12 years old. It was found that

there was an improvement in AD scores (SCORAD), with

a concomitant decrease in IFN-γ, eosinophil, and

Interleukin-4 counts (Han et al., 2012).

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The effect of Lactobacillus rhamnosus in the

management of AD has been assessed by Kalliomaki et al.

(2001) in a double-blind, placebo-controlled, randomized

trial. In this trial 159 pregnant women with a family history

of allergic disorders such as asthma, allergic rhinitis or

eczema received placebo or Lactobacillus rhamnosus for 2

to 4-weeks before delivery and for a 6 month period after.

The percentage of children aged 2 years old with atopic

eczema was 23% in the probiotic group and 46% on

placebo (p= 0.008). A subgroup analysis conducted on 57

breastfed infants confirmed the benefit of a defensive effect

against eczema from supplementation with Lactobacillus

rhamnosus (Rautava, 2002). In recent trials by Wickens et

al., supplementation with Lactobacillus rhamnosus HN001

or Bifidobacterium lactis HN019 to mothers and infants

showed a significant protective effect only in the groups

receiving the supplementation with Lactobacillus

rhamnosus HN001 by 2 years of age (Wickens et al., 2008)

and 4 years of age (Wickens et al., 2012). The reported data

suggest that many probiotics may share common properties

but their effect may be strain-specific (Allen et al., 2003).

For instance, Gruber et al. (2007) found that

Lactobacillus rhamnosus strain GG (LGG) exerted no

therapeutic effects in infants with mild-to-moderate AD.

Another randomized, double-blind, placebo controlled

study investigated the use of L. paracasei (LP), L.

fermentum (LF), and LP+LF together in children, and it

was observed that the SCORAD scores were lower in the

group that received probiotics than those of the placebo

group 4 months after discontinuing the probiotic treatment

(Wang and Wang, 2015).

Sistek et al. (2006) conducted a 12-week trial in the

UK and found that a combination of LR and Bifidobacteria

lactis (BL) improved AD symptoms in food-sensitive

children.

Woo et al. (2010) compared children who received L.

sakei supplementation to those who received a placebo in

a double-blind, placebo-controlled trial. It was found that

the supplementation of L. sakei was associated with

substantial clinical improvement with concomitant

decrease in chemokine levels.

Gerasimov et al. (2010) reported that Lactobacillus

acidophilus DDS-1 and Bifidobacterium lactis UABLA-12

afforded significant clinical improvements in children with

moderate-to-severe AD.

A prospective, double-blind, placebo-controlled study

tested a lotion containing 5% of nonpathogenic Vitreoscilla

filiformis lysate. Seventy-five volunteers with AD applied

the lotion or placebo twice a day for 30 days. Then, the

severity of the disease (Scoring Atopic Dermatitis –

SCORAD), the transepidermal water loss, the microbiome,

and the patient’s report on itchiness and slvitreoscieep loss

were evaluated. The lysate has significantly improved AD

in all evaluated items, reducing skin colonization by S.

aureus. Authors concluded that the results are not only

because of S. aureus bacterial load reduction but also

immunomodulatory effect on the skin. Later, the lysate’s

immunomodulatory action was proved through analysis of

dendritic cells differentiation and effector functions of

dendritic and T-helper cells in vitro and in vivo. The topical

treatment with the bacteria significantly reduced

inflammation in mice, and the combination of allergen and

lysate showed lower induced dermatitis, indicating active

immunomodulation. It was observed that the innate

sensibility of nonpathogenic bacteria for Toll-Like

Receptor 2 (TLR2) induces dendritic tolerogenic cells and

Tr1 regulatory cells, suppressing T-effector cells and

cutaneous inflammation (Gueniche et al., 2008).

A revision performed by Sikorska and Smoragiewicz

(2013) found a series of evidence that various strains of

Lactobacillus and Bifidobacterium isolated from a variety

of sources inhibit in vitro growth of S. aureus. The most

active strains were Lactobacillus reuteri, Lactobacillus

rhamnosus GG, Propionibacterium freudenreichii, P.

acnes, L. paracasei, L. acidophilus, L. casei, Lactobacillus

plantarum, Lactobacillus bulgaricus, Lactobacillus

fermentum, and Lactococcus lactis. This revision also

included evidence that probiotics may also eliminate or

reduce colonization of methicillin-resistant S. aureus.

According to authors, their effects are mediated by both

cellular competitive exclusion and acid or Bacteriocin-

Like Inhibitors’ secretion.

Administration of the strain Bifidobacterium dentium

in mothers from 36-week gestation to 3 months post-

partum reduced the incidence of AD in offspring by 40%.

The group responding to the probiotic intervention had a

gut microbiota similar to the non-atopic children

(Avershina et al., 2017).

In a randomized double blind control trial using

Lactobacillus rhamnosus HN001 or Bifidobacterium lactis

HN019 taken (dose 6X109 colony-forming units (CFU)

daily) from 35 weeks of gestation to 6 months post-partum

in mothers while breastfeeding and from birth to age 2

years in infants, the authors showed that HN001

significantly protected against the development of eczema

at 2, 4, 6, and 11 years and atopic sensitization at 6 years,

while the strain HN019 had no significant effect on these

outcomes (Wickens et al, 2018).

In a randomized double blind control trial from 36

weeks of gestation until 3 months’ post-partum, 415

pregnant women were randomized to receive either

probiotics (LGG, L acidophilus La-5, and B animalis subsp

lactis Bb-12 dose: 5 × 1010 CFU daily) or placebo. At 6

years, there was a trend toward a lower cumulative

incidence of AD in the probiotic group, but the prevalence

of asthma and atopic sensitization was not significantly

affected by the probiotic regime (Simpson MR et al.,

2015). In a RDBCT, a total of 290 participants were

randomized to receive a daily mixture of LGG and B

animalis subsp lactis BB-12 each at a dose of 109 CFU, or

placebo. During the follow-up (mean age: 16.1 months), a

significantly lower incidence of eczema was observed in

the probiotic group (Schmidt et al., 2019).

Probiotic’s mechanism of action in atopic dermatitis

relies on their immunomodulatory effect, normalizing

microbial composition and metabolic effect. The

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Maced. pharm. bull., 68 (1) 9 – 26 (2022)

immunomodulatory effect is achieved by their ability to

inhibit the T-helper cell type 2 (Th2) mediated response and

improve the Th1/Th2 ratio; inhibiting Th2 cell response,

cytokines such as IL-4, IL-5, IL-6 and IL-13 are no longer

released, (Nwanodi, 2018) phagocytosis is stimulated,

serum IgA is increased. Probiotics can reduce inflammation

by reducing proinflammatory cytokines, IL4, IL6, tumor

necrosis factor-α (TNF-α), INF-γ and high sensitivity C

reactive protein (hsCRP) and by increasing expression of

IL-10 and Treg-related cytokines at mesenteric lymph

nodes. A new mechanism proposed to demonstrate the

effectiveness of probiotics is the inhibition of the mature

dendritic cell differentiation and transformation of naive T

cells into Th2. Immunomodulation decreases the

susceptibility to inflammatory and allergic factors

modulating the intestine skin axis. Probiotics also modulate

brain function including stress response on the intestine-

brain axis in rats and human subjects (Messaoudi M. et al.,

2010). Normalization of microbial composition provides

protection against pathogens at the mucosal surface. It has

been shown that the levels of Bifidobacterium longum in

the feces of healthy children were significantly higher than

in children with allergy, suggestigLDEng the role of this

strain in preventing the occurrence of bronchial asthma and

allergic dermatitis (Akay, 2014).

The metabolic effect via probiotic consumption, can

be associated with the reduction of blood glucose,

insulinemia and insulin resistance.

Psoriasis

Psoriasis is a systemic inflammatory disease

characterized by scaly lesioned plaques with defined

borders. These lesions are mainly located on the scalp and

large areas of the extremities but can occur at any site of the

body. The prevalence of psoriasis is around 1–3%, with

differences between countries, corresponding the highest

prevalence to Western countries.

The etiopathogenesis of psoriasis is not fully known,

although most authors postulate that it would be a skin

disorder of genetic origin, finally triggered by external

factors that would cause changes at the immune level. The

disease is associated with inflammation in other systems

and organs, as evidenced by the fact of finding a correlation

with inflammatory bowel disease, where between 7 and

11% of diagnosed patients also suffer from psoriasis. Other

components as triggers of psoriasis are age, the

comorbidity, environmental and external factors.

Although data on probiotic supplementation in

psoriasis treatment are limited, promising outcomes have

been documented with oral probiotics interventions, and

more studies are needed to explore the role of topical

probiotics in psoriasis therapy.

Immune regulation

One of the most important properties required for a

potential probiotic strain is the capacity of sticking to the

epithelial cells. In this regard, Galdeano et al. (2006)

demonstrated using electronic microscopy that 2 probiotic

microorganisms, L. casei CRL 431 and L. paracasei CNCM

I-1518, adhere to the intestinal epithelial cells (IECs)

through the Toll-like receptors (TLRs) and mediate

immune stimulation. Following this interaction, an increase

in the cytokines production such as IL-6 and macrophage

chemoattractant protein 1 from the IECs occurred, without

altering the intestinal barrier; only a slight increase in the

mononuclear cell infiltration of small intestine was

observed. The authors also demonstrated that only

fragments of the probiotic bacteria, and not the whole

bacteria, were internalized inside the IECs. As a

consequence, the IECs initiate a complex network of

signals that stimulate the immune cells associated with the

lamina propria and activate mainly the innate response and

the cytokines released by T cells.

The immunomodulatory effect of probiotics is

attributed to the release of cytokines, including interleukins

(ILs), tumor necrosis factors (TNFs), interferons (IFNs),

transforming growth factor (TGF), and chemokines from

immune cells (lymphocytes, granulocytes, macrophages,

mast cells, epithelial cells, and dendritic cells (DCs))

(Savan et al., 2006) which further regulate the innate and

adaptive immune system (Follign’e et al., 2010). In

addition, two surface phagocytosis receptors (FcRIII and

tool-like receptor (TLR)) are also upregulated by NO

(Delcenserie et al., 2008; Schwandner et al., 1999).

Probiotics have been reported to interact with enterocytes

and dendritic, T1, T2, and Treg cells in the intestine and to

modulate the adaptive immunity into pro- and/or anti-

inflammatory action. Studies with BALB/c (20–30 g)

inbred mice and Fisher-344 inbred rats demonstrated that

Lactobacillus paracasei subsp. Paracasei DC412 strain

and L. acidophilus NCFB 1748 induced early innate

immune responses and specific immune markers through

phagocytosis, polymorphonuclear (PMN) cell recruitment,

and TNFalpha (TNF-α) production (Kourelis A. et al.,

2010). In another experimental animal model involving

BALB/c mice, oral administration of L. casei favored rapid

activation of immune cells and produced a higher number

of specific markers such as CD-206 and TLR2 cells

(Galdeano et al., 2006), while TLRs improve the

immunological defense mechanism in terms of pro- and

anti-inflammatory cytokine production upon the detection

of foreign objects (Anderson, 2000).

One of the ways probiotics promote human health is

by inhibiting the growth of pathogenic bacteria through the

synthesis of low molecular weight compounds such as

organic acid and large molecular weight antimicrobial

compounds termed bacteriocins. Organic acids are acetic

and lactic acids. These compounds have been proven to

exhibit strong inhibitory effects against pathogenic gram-

negative bacteria such as H. pylori. Some bacteriocins

produced by probiotics are lactacin B from L. acidophilus,

bifidocin B produced by Bifidobacterium bifidum NCFB,

plantaricin from L. plantarum, and nisin from Lactococcus

lactis.

Probiotics modulate the composition of gut microbial

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species by maintaining the balance and suppressing the

growth of potential pathogenic bacteria in the gut. It has

been reported that L. acidophilus or L. casei increased LAB

with a concomitant decrease of fecal coliforms and

anaerobes. In addition, a study by Li et al. (2016) found

that probiotics caused shifts in the gut microbiota

composition toward specific beneficial bacteria, for

example, Prevotella and Oscillibacter. These bacteria are

known to produce anti-inflammatory metabolites, which

subsequently decreased the Th17 polarization and favored

the differentiation of anti-inflammatory Treg/Type 1

regulatory T (Tr1) cells in the gut.

Wound healing

Skin microorganisms contribute to the host immunity

via different pathways. S. epidermidis has been shown to

boost the host immunity by inducing AMPc such as β

defensins 2 and 3 to S. aureus, by activating mast cell-

mediated antiviral immunity, by suppressing uncontrolled

inflammatory reactions during wound healing, inducing

skin’s AMP production and by stimulating cutaneous T-

cell maturation.

The use of Lactobacillus plantarum as a potential

therapeutic agent for the local treatment of Pseudomonas

aeruginosa burn infections have shown positive results.

The same bacteria has been investigated for the treatment

of non-diabetic and diabetic ulcers. Peral et al. (2009)

found that it reduced bacterial load, neutrophils, and

apoptotic and necrotic cells, modified interleukin-8

production, and induced wound healing.

Regulatory aspects (labeling, marketing)

The U.S. Food and Drugs Administration (FDA)

categorizes probiotics into different categories, such as

dietary supplements, foods, food additives, cosmetics, or

drugs, based on each individual product. However, there is

no regulation for topical probiotics, and currently there are

no topical probiotic products approved by the FDA, which

shows a need to improve the regulations for these products.

There are scores of topical cosmetic probiotic skin care

products marketed and sold in the U.S., and the number

continues to grow. While there is no restriction on

including probiotics in cosmetic products, and FDA pre-

market approval is not required, companies must still

ensure their products are safe before they are marketed to

consumers. In addition to testing for safety, products that

include live microorganisms should be tested to ensure

stability for the anticipated life of the product under normal

use indications. FDA continues to evaluate scientific data

on the safety of probiotics, but, as of the date of

publication, has not issued any guidance documents

addressing the use of such ingredients in cosmetics.

As with any other cosmetic product, companies that

market topical probiotic skin care products are proscribed

from claiming the product affects the structure or function

of the body; such claims effectively convert a product from

a legally marketed cosmetic into an unapproved drug. For

example, claims that a probiotic skin care product can

reverse the signs of aging, stimulate the growth of collagen

and elastin, or treat acne are structure/function claims that

cannot be used to legally market cosmetics in the U.S.

While a number of company’s market probiotic cosmetic

products making such claims, they do so at their peril and

run the risk FDA will categorize the products as

unapproved adulterated drugs that cannot lawfully be

marketed in the U.S. without pre-market approval. To

avoid regulatory challenges and possible product recall,

companies marketing probiotic skin care products should

ensure all product claims are truthful and not misleading

and refrain from making structure/function or disease

claims on the product label or labeling accompanying the

product, as well as on company web sites and social media

accounts.

In the EU, as with all cosmetics, prebiotics, probiotics

and postbiotics must meet key cosmetic principles.

However, there is still no specific regulation or guidelines

regarding these cosmetically active substances in relation

to the microbiome. Namely, although the skin microbiota

cannot be separated from the skin, in cosmetic regulation,

skin microbiome / microbiota not yet defined, it is not even

described. However, the expectation is that scientific

results will be implemented in the regulation for cosmetic

products and the basic ones will be introduced definitions

and security aspects. Most importantly, it should be noted

that these cosmetic substances are not prohibited (for

example, not listed in Annex II of EC12323 / 2009) and

can therefore be used safely. Therefore, they can be

considered for "classic" substances, which clearly indicates

the need to comply with cosmetics definition and key

principles.

Prebiotics and postbiotics can be used and are already

used as cosmetics substances. Probiotics, when used in

cosmetics, have in order to protect the skin from external

influences and to feed healthy bacteria for affect the pH or

hydration of the skin, for example. Consequently, in the

absence of a cosmetic policy on probiotics, living

organisms may for the time being are considered classic

cosmetic ingredients that fall under the general definition

of cosmetic raw materials.

It is worth mentioning that the Voluntary International

Group of Regulatory Authorities for Cosmetics

(International Cooperation on Cosmetics Regulation - from

Brazil, Canada, China, EU, Japan, Republic of Korea and

USA) in 2018 formed a joint working group precisely in

order to examine in detail the probiotic-based products in

the cosmetics sector. Based on the observations, the group

was identified the potential need to develop internationally

accepted terminology guidelines, safety and quality of

these substances in cosmetic products.

In this regard, it is important to emphasize the

cosmetic key principles and their association when it

comes to probiotics as active substances. Namely, if we

E. Hyseni, M. Glavas Dodov

Maced. pharm. bull., 68 (1) 9 – 26 (2022)

look at the cosmetic regulatory framework, each country

has its own definition of what 31 is a cosmetic product but

has similarities in criteria such as location of application

and cosmetic function. As such, to be considered a cosmetic

product, the product must contain the following:

Place of application: The product must be used on the

outside of the body, e.g. epidermis, nails, teeth, hair, lips

and external genitalia organs.

Function: The function of the product should be to

clean, beautify, correct body odors or otherwise to keep the

body in good condition. While probiotic-based products

meet the above criteria above, cosmetic key principles

include additional factors such as safety, microbiological

quality and permissible claims, as well as shelf life and

packaging.

Safety: The cosmetic product (and its ingredients)

must be safe for its intended use. Safety assessment is a

mandatory requirement in EU cosmetics legislation (and

widely sought after by companies and regulators in North

America, ASEAN countries and China) as proof that the

product is safe to use. Security is the responsibility of

industry. Probiotics are living organisms that are dynamic

and therefore different from other cosmetic substances.

Hence, in the cosmetics industry there is a need to adjust

and design a safety assessment applicable to cosmetics

based on probiotic. For example, it is essential to prove that

the microorganism used does not produce toxins, to prove

the absence of pathogenicity and to determine antibiotic

resistance and metabolic activity (common criteria for a

similar safety assessment as in the food sector).

Microbiological quality: Cosmetic products are not

expected to be sterile, but they still must meet the

microbiological quality requirements (total number of

aerobic mesophilic microorganisms (bacteria, yeasts and

molds) and the absence of specific microorganisms

(Candida albicans, Staphylococcus aureus, Pseudomonas

aeruginosa, Escherichia coli). It is described in the

instructions of EU Scientific Committee on Consumer

Safety (SCCS): even if it is not legally required, this

microbiological test is necessary to guarantee the quality of

the cosmetic product and the safety of the consumer

(Regulation (EC) No 1223/2009 of the European

Parliament and of the Council of 30 November 2009 on

cosmetic products).

Hence, it remains unclear how well probiotics meet

the requirements for microbiological quality that generally

applies to all cosmetic products. Microorganisms are

generally considered contaminants, with a focus on

pathogens microorganisms, because cosmetics are

formulated to minimize their growth. Therefore, it is

important to educate both cosmetic companies and

consumers/patients about the specifics when it comes to

probiotics as active substances in cosmetics products.

Claims: Cosmetic claims must be confirmed, not false

or unproven. In the context of naming a particular product

as a probiotic, that means that the final manufactured

cosmetic product must contain probiotics and most

importantly, probiotics must be alive throughout shelf life

of the product. However, more and more products on the

market contain claims to contain probiotic ingredients, but,

as already mentioned, research has shown that many of

these products on the market contain primarily postbiotics

and prebiotics, not live bacteria. As a result, inappropriate

use of various undefined terms (probiotic, prebiotic and

postbiotic) creates confusion about these products.

It is therefore clear that it is necessary to develop

internationally accepted definitions of key terms that need

to be used consistently in order to minimize confusion and

to avoid misunderstanding, both with regulators and

consumers. In the food and food supplements industry,

each European country has its own country-specific

labeling rules, but in some European countries

manufacturers cannot even put the word "probiotic" on the

label of the product.

For all the above reasons, the joint working group

“Microbiome and ICCR's Cosmetics” works to educate key

stakeholders (regulatory bodies, cosmetics industry and

consumers) in order to achieve a better understanding and

augmentation.

Conclusion

Topical probiotics are definitely a promising range of

products in treating various skin conditions. It has been

demonstrated that different probiotics strains can help

improve the outcomes of acne, atopic dermatitis, psoriasis,

wound healing, oral and intimate care, but there is yet a lot

to be understood.

The lack of knowledge regarding skin’s microbiome,

the site-specific diversity of microorganisms makes it

difficult for topical probiotics developers to achieve the

desired formulation. The optimal dosage and strain for

various skin conditions has yet to be determined. However,

there is enough topical probiotics evidence to keep

searching new ways or strains to achieve their full potential

worth it.

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Резиме

Пробиотици во дерматолошки и козметички

производи - употреба и ефикасност

Едита Хисени и Марија Главаш Додов*

Центар за фармацевтска нанотехнологија, Фармацевтски факултет,

Универзитет „Св. Кирил и Методиј“, Мајка Тереза 47, 1000 Скопје, С. Македонија

Клучни зборови: пробиотици, акни, атопичен дерматитис, фотостареење, псоријаза, имунолошки систем,

заздравување на рани, орална нега, интимна нега, микробиом на кожатa

Терминот „пробиотици“ првпат е употребен во 1907. година од страна на Ели Мечникоф. Оттогаш,

пробиотиците се дел од истражувањата не само за дигестивното здравје, туку и за воспалителните болести. Во

последно време, постои зголемен интерес за ефектите на пробиотиците во негата на кожата. Третирањето на

атопичен дерматитис, акни, псоријаза, фото стареење, рак на кожата, спроведувањето на интимна нега, орална

нега, како и заздравувањето на раните е сѐ потешко, поради зголемената резистентност кон антибиотиците и

другите несакани ефекти од конвенционалната терапија. Согласно претходно наведеното, резултатите од многу

истражувања покажуваат дека пробиотиците се ефикасни во лекувањето на различни кожни заболувања.

Овој преглед има за цел да ги оцени научните докази за локални и орални пробиотици и да ја оцени

ефикасноста на козметичките и дерматолошките производи кои содржат пробиотици. Многу студии покажале дека

промените на микробиомот на кожата и цревата имаат важна улога во здравјето на кожата. Иако ова е нова тема

во дерматологијата и козметологијата, постојат ветувачки резултати добиени од многу истражувачки студии во

однос на подобрување на исходот на пациентот при употребата на пробиотици во козметичките производи. И

покрај тоа што, оралните пробиотици е покажано дека го промовираат здравјето на цревата, што влијае на

имунолошкиот систем на домаќинот и помага во лекувањето на различни кожни болести, механизмот на дејство

на локалните пробиотици сè уште не е целосно разбран. Иако бројот на комерцијални пробиотски козметички

производи достапни на пазарот се зголемува и повеќето од студиите не покажале сериозни несакани ефекти од

пробиотиците, потребно е да се спроведат дополнителни студии, во поголеми и хетерогени групи.

Current Approaches in Cosmeceuticals: Peptides, Biotics and Marine Biopolymers

Article

Full-text available

Mar 2025

Today’s consumer perception and expectations of personal care have gone beyond merely cleansing, moisturizing, and makeup products, focusing more on the reduction or elimination of signs of aging. Cosmeceuticals, developed to create a more youthful appearance, commonly contain substances with therapeutic and physiological effects. The development of cosmeceutical products containing peptides, biotic ingredients, and marine-based compounds has become a highly popular strategy to enhance anti-aging effects and better address consumer demands. Peptides are frequently used in anti-aging products due to their effects on enhancing fibroblast proliferation and collagen synthesis, contributing to the skin’s barrier function, and reducing skin pigmentation. Meanwhile, biotic components are extensively evaluated for their potential to improve barrier function by maintaining the balance of the skin microflora. On the other hand, the increasing interest of cosmetic consumers in natural and eco-friendly products, along with the rich biodiversity in the oceans and seas, has made marine-derived substances highly significant for the cosmetic industry. Marine polysaccharides are particularly valuable as biopolymers, offering useful properties for gel formation in cosmetic formulations. This review discusses scientific studies and commercially available products using peptides, biotic and marine-based compounds in cosmetic formulations, their cosmetic and cosmeceutical benefits, and the challenges in the formulation design of these products.

Role of probiotics in skin health: Current trends and future perspectives

Article

Full-text available

Jan 2025

The human skin is a complex ecosystem that plays a crucial role in maintaining overall health and well-being. In recent years, there has been a growing interest in the potential benefits of probiotics in promoting skin health. Probiotics are live microorganisms that confer health benefits when administered in adequate amounts. Probiotics have been shown to have a positive impact on the skin microbiome, promoting the growth of beneficial microorganisms and inhibiting the growth of pathogens. In addition to their effects on the skin microbiome, probiotics have also been shown to have anti-inflammatory, antioxidant, and immune-modulating effects, which may contribute to their beneficial effects on skin health. Their role in skin health is a relatively new area of research. This review aims to provide an overview of the current state of knowledge on the role of probiotics in skin health, including their potential benefits, mechanisms of action, and future perspectives.

In Vitro Exploration of the Multi-Functional Dermatological Benefits of a Lactobacillus-Turmeric Synbiotic

Article

Mar 2025

Revolutionizing Cosmetic Ingredients: Harnessing the Power of Antioxidants, Probiotics, Plant Extracts, and Peptides in Personal and Skin Care Products

Article

Full-text available

Sep 2024

The burgeoning interest in natural components in personal care products has led to significant research and development of ingredients such as plant extracts, antioxidants, peptides, and probiotics. These components have been recognized for their potential to enhance skin health through various mechanisms, addressing consumer demand for products that are both effective and benign. Plant extracts, known for their rich composition of bioactive compounds, offer a myriad of benefits including antioxidant, anti-inflammatory, and antimicrobial properties, making them invaluable in skin care formulations. Antioxidants, derived from both plants and other natural sources, play a pivotal role in protecting the skin from oxidative damage, thereby preventing premature aging and promoting skin vitality. Bioactive peptides have garnered attention owing to their multifunctional activities that include promoting collagen synthesis, inhibiting enzymes responsible for skin degradation, and reducing inflammation, thereby contributing to skin regeneration and anti-aging. Probiotics have expanded their utility beyond gut health to skin care, where they help in maintaining skin microbiome balance, thus enhancing skin barrier function and potentially mitigating various skin disorders. The purpose of this review is to explore the individual roles of plant extracts, antioxidants, peptides, and probiotics in personal care products, while emphasizing their synergistic effects when combined. By integrating these natural components, this paper aims to highlight the potential for developing innovative skincare formulations that not only address specific skin concerns but also contribute to overall skin health, aligning with the increasing consumer preference for natural and holistic skincare solutions.

Applications of Synbiotics as Cosmeceuticals

Chapter

Mar 2024

Acne, Microbiome, and Probiotics: The Gut–Skin Axis

Article

Full-text available

Jun 2022

The objective of this narrative review was to check the influence of the human microbiota in the pathogenesis of acne and how the treatment with probiotics as adjuvant or alternative therapy affects the evolution of acne vulgaris. Acne is a chronic inflammatory skin disease involving the pilosebaceous units. The pathogenesis of acne is complex and multifactorial involving genetic, metabolic, and hormonal factors in which both skin and gut microbiota are implicated. Numerous studies have shown the bidirectionality between the intestinal microbiota and skin homeostasis, a communication mainly established by modifying the immune system. Increased data on the mechanisms of action regarding the relevance of Cutibacterium acnes, as well as the importance of the gut–skin axis, are becoming known. Diverse and varied in vitro studies have shown the potential beneficial effects of probiotics in this context. Clinical trials with both topical and oral probiotics are scarce, although they have shown positive results, especially with oral probiotics through the modulation of the intestinal microbiota, generating an anti-inflammatory response and restoring intestinal integrity, or through metabolic pathways involving insulin-like growth factor I (IGF-1). Given the aggressiveness of some standard acne treatments, probiotics should continue to be investigated as an alternative or adjuvant therapy.

Skin Protective Activity of LactoSporin-the Extracellular Metabolite from Bacillus Coagulans MTCC 5856

Article

Full-text available

Oct 2020

Background: Probiotics and their products are increasingly used in skincare in recent years. Postbiotics are defined as any substance derived through the metabolic activity of a probiotic microorganism, which exerts a direct or indirect beneficial effect on the host. The extracellular metabolites of probiotic bacteria have antimicrobial activities, protect against acne, and improve skin condition. We studied skin protective activities of the extracellular metabolite (LactoSporin) of a spore-forming probiotic Bacillus coagulans MTCC 5856 in vitro. Methods: LactoSporin was evaluated for antioxidant activity by free radical scavenging activity and reactive oxygen quenching activity in human dermal fibroblast cells. Protection of fibroblasts from UV-induced apoptosis and cell death was studied by flow cytometry and neutral red uptake assays. Enzyme inhibition assays were carried out for collagenase, Elastase, and Hyaluronidase. Gene expression studies were carried out using polymerase chain reaction. Results: LactoSporin showed antioxidant activity and was found to protect skin cells from UV-induced apoptosis and cell death. LactoSporin inhibited collagenase, elastase, and hyaluronidase activity and upregulated the expression of hyaluronan synthase, transforming growth factor and epidermal growth factor, which are associated with extracellular matrix integrity. Conclusions: These results suggest LactoSporin is a skin protective postbiotic with wide application in cosmetic formulations.

Novel Topical Application of a Postbiotic, LactoSporin®, in Mild to Moderate Acne: A Randomized, Comparative Clinical Study to Evaluate its Efficacy, Tolerability and Safety

Article

Full-text available

Sep 2020

Acne vulgaris is a common skin disorder of pilosebaceous units. The therapy for mild-to-moderate acne includes topical antibiotics, benzoyl peroxide and retinoids. In this open-label, randomized monocentric study, we compared the efficacy of LactoSporin® 2% w/w cream with benzoyl peroxide in 64 male and female subjects with mild-to-moderate acne for three weeks. The efficacy parameters were evaluated based on the dermatologist visual assessment and instrumental measurements using Sebumeter® MPA580, Antera 3DTM and VISIA CR 2.2 and subject self-assessment questionnaires. Adverse events were recorded throughout the study period. In order to understand the mechanism of action and properties of LactoSporin, the pH stability, thermostability, antimicrobial activity and 5-alpha reductase activity were evaluated in vitro. A significant improvement was observed in the dermatological assessment of closed comedones (p < 0.0001), open comedones (p = 0.0069) and papules count (p < 0.0001) in comparison to the baseline in both LactoSporin and benzoyl peroxide groups. The antera analysis showed significant improvement in redness (p < 0.0001) and elevation (p < 0.0001) (small and medium) in both the treatment groups. The sebumeter analysis showed a significant decrease in sebaceous secretion (p < 0.0001) for LactoSporin, which resulted in reduced oiliness, pimples, acne spots and redness around the acne spot. The product was found to be safe without any irritancy. LactoSporin was stable at an acidic pH and temperature range of 70 to 90 °C, with antimicrobial activity against various pathogenic bacteria, including Cutibacterium acnes. It was also a potent inhibitor of 5-alpha reductase activity. Thus, it can be concluded that the efficacy of LactoSporin is equivalent to benzoyl peroxide in the treatment of mild-to-moderate acne lesions and better than benzoyl peroxide for reducing the sebaceous secretion and oily, greasy nature of the skin, implying its efficacy in other sebohorriec conditions.

The Skin Microbiome: A New Actor in Inflammatory Acne

Article

Full-text available

Sep 2020
AM J CLIN DERMATOL

Our understanding of the role of Cutibacterium acnes in the pathophysiology of acne has recently undergone a paradigm shift: rather than C. acnes hyperproliferation, it is the loss of balance between the different C. acnes phylotypes, together with a dysbiosis of the skin microbiome, which results in acne development. The loss of diversity of C. acnes phylotypes acts as a trigger for innate immune system activation, leading to cutaneous inflammation. A predominance of C. acnes phylotype IA1 has been observed, with a more virulent profile in acne than in normal skin. Other bacteria, mainly Staphylococcus epidermis, are also implicated in acne. S. epidermidis and C. acnes interact and are critical for the regulation of skin homeostasis. Recent studies also showed that the gut microbiome is involved in acne, through interactions with the skin microbiome. As commonly used topical and systemic antibiotics induce cutaneous dysbiosis, our new understanding of acne pathophysiology has prompted a change in direction for acne treatment. In the future, the development of individualized acne therapies will allow targeting of the pathogenic strains, leaving the commensal strains intact. Such alternative treatments, involving modifications of the microbiome, will form the next generation of 'ecobiological' anti-inflammatory treatments.

Skin Microbiome and its Interplay with the Environment

Article

Full-text available

Sep 2020
AM J CLIN DERMATOL

Advances in sequencing, bioinformatics and analytics now allow the structure, function and interrelations of whole microbial communities to be studied in greater detail. Collaborative efforts and multidisciplinary studies, crossing the boundary between environmental and medical microbiology, have allowed specific environmental, animal and human microbiomes to be characterized. One of the main challenges for microbial ecology is to link the phylogenetic diversity of host-associated microbes to their functional roles within the community. Much remains to be learned on the way microbes colonize the skin of different living organisms and the way the skin microbiome reacts to the surrounding environment (air, water, etc.). In this review, we discuss examples of recent studies that have used modern technology to provide insights into microbial communities in water and on skin, such as those in natural resources (thermal spring water), large mammals (humpback whales) and humans (the skin microbiome). The results of these studies demonstrate how a greater understanding of the structure and functioning of microbiota, together with their interactions with the environment, may facilitate the discovery of new probiotics or postbiotics, provide indicators for the quality of the environment, and show how changes in lifestyle and living environment, such as urbanization, can impact on the skin microbiome and skin health and disease in humans.

The potential of probiotics for treating acne vulgaris: A review of literature on acne and microbiota

Article

Full-text available

Apr 2020
DERMATOL THER

Acne is known as a chronic inflammatory skin disease with sever adverse effects on quality of life in the patients. The increasing resistance to antibiotics has decreased their effectiveness in treating acne. As viable microbial dietary supplements, probiotics provide health benefits through fighting pathogens and maintaining the homeostasis of the gut and skin microbiome. The present article reviewed the potential of probiotics as beneficial microorganisms for treating acne vulgaris. This review of literature was conducted through a bibliographic search of popular databases, including Science Direct, PubMed, Scielo and Medline, using keywords such as probiotics, prebiotics, synbiotics, microbiome, and acne vulgaris to determine potential applications of these beneficial microbiomes in treating acne vulgaris. Acne lesions are associated with increases in proportion of Propionibacterium acnes as a skin commensal bacterium. The environmental studies showed inhibitory effects of probiotics on P. acnes, mediating by antibacterial proteins and bacteriocin‐like inhibitory substances, and their immunomodulatory effects onkeratinocytes and epithelial cells. Probiotics were also found to inhibit cytokine IL‐8 in epithelial cells and keratinocytes, suggesting immunomodulatory activities. Moreover, glycerol fermentation by Staphylococcus epidermidis was found to be a natural skin defense against acne and an overgrowth inhibitor of P. acnes. As an antimicrobial agent in lotions and cosmetic formulations, Lactococcus sp. can decrease the inflammatory mediators that are produced by P. acnes and cause vasodilation, edema, mast cell degranulation and TNF‐alpha release. Oral administration of probiotics was found to constitute an adjuvant therapy to conventional modalities for treating mild‐to‐moderate acne vulgaris.

Anti-Photoaging Effect of Plant Extract Fermented with Lactobacillus buchneri on CCD-986sk Fibroblasts and HaCaT Keratinocytes

Article

Full-text available

Jan 2020

Ultraviolet (UV) exposure triggers the abnormal production of reactive oxygen (ROS) species and the expression of matrix metalloproteinases (MMPs) that are responsible for photoaging. Probiotics are widely used in healthcare and for immune enhancement. One probiotic, Lactobacillus buchneri is found in Kimchi. This study was aimed at assessing the anti-photoaging effect of plant extracts fermented with L. buchneri (PELB) to develop functional cosmetics. We investigated the anti-photoaging effect of PELB in a UVB-induced photoaging in vitro model and selected effective extracts using the elastase inhibition assay, ELISA for Type I procollagen and collagenase-1, and quantitative real time PCR. Normal human dermal fibroblasts and epidermal keratinocytes were pre-treated with PELB and exposed to UVB. We found that PELB decreased elastase activity and increased type I collagen expression in a UVB-induced photoaging in vitro model. In addition, PELB greatly reduced collagenase activity and MMP mRNA levels in a UVB-induced photoaging in vitro model. Furthermore, PELB promoted the expression of moisture factor and anti-oxidant enzymes in a UVB-induced photoaging in vitro model. These results indicated that the PELB could be potential candidates for the protective effects against UVB-induced photoaging. Overall, these results suggest that PELB might be useful natural components of cosmetic products.

Regulation of Probiotic and Other Live Biologic Products

Article

Sep 2020

This chapter discusses the regulation of probiotic products in the United States. In the U.S, the intended use determines how a product is regulated. Products marketed to treat or prevent disease are regulated as drug or biologic products. Ingestible products, other than conventional foods, marketed to supplement the diet are regulated as dietary supplements while topical products that are designed to cleanse or beautify the body are regulated as cosmetics. The Federal Food and Drug Administration (FDA) is the primary agency responsible for regulating drugs, foods (including dietary supplements), and cosmetics. The Federal Trade Commission (FTC) shares jurisdiction with FDA and is the agency charged with ensuring that products are marketed truthfully and claims are properly substantiated. The myriad of U.S. regulations pursuant to which these agencies exercise their regulatory oversight of probiotic products is discussed below.

MONOCLONAL ANTIBODY THERAPIES for Atopic Dermatitis: Where Are We Now in the Spectrum of Disease Management?

Article

Feb 2019

James Q Del Rosso

Atopic dermatitis (AD) is a chronic disorder that requires thorough patient education and a therapeutic management strategy designed to control flares, decrease recurrences, and reduce pruritus. In cases that cannot be controlled by proper skin care and barrier repair, topical therapy, and avoidance of triggers, systemic therapy is often required to control flares and maintain remission. It is important for clinicians to avoid becoming overly dependent on the intermittent use of systemic corticosteroid therapy to control flares, without incorporating other treatment options that might more optimally control AD over time. This article provides an overview of systemic therapies, including conventional oral therapy options and injectable biologic agents, that modulate the immune dysregulation in AD. Major emphasis is placed on the monoclonal antibodies currently available (e.g., dupilumab) for the treatment of AD, as well as those in latter stages of development, with a focus on agents targeting IL-4and/or IL-13.

Atopic Dermatitis: Diagnosis and Treatment

Article

May 2020

Atopic dermatitis (atopic eczema) is a chronic relapsing and remitting inflammatory skin disease affecting one in 10 people in their lifetime. Atopic dermatitis is caused by a complex interaction of immune dysregulation, epidermal gene mutations, and environmental factors that disrupts the epidermis causing intensely pruritic skin lesions. Repeated scratching triggers a self-perpetuating itch-scratch cycle, which can have a significant impact on the patient's quality of life. The American Academy of Dermatology has created simple diagnostic criteria based on symptoms and physical examination findings. Maintenance therapy consists of liberal use of emollients and daily bathing with soap-free cleansers. Use of topical corticosteroids is the first-line treatment for atopic dermatitis flare-ups. Pimecrolimus and tacrolimus are topical calcineurin inhibitors that can be used in conjunction with topical corticosteroids as first-line treatment. Ultraviolet phototherapy is a safe and effective treatment for moderate to severe atopic dermatitis when first-line treatments are not adequate. Antistaphylococcal antibiotics are effective in treating secondary skin infections. Oral antihistamines are not recommended because they do not reduce pruritus. Evidence is lacking to support the use of integrative medicine in the treatment of atopic dermatitis. Newer medications approved by the U.S Food and Drug Administration, such as crisaborole and dupilumab, are effective in treating atopic dermatitis but are currently cost prohibitive for most patients.

Probiotics in dermatological and cosmetic products – application and efficiency

Abstract

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