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Received: 13 February 2020 Accepted: 18 February 2020
DOI: 10.1111/dth.13279

REVIEW ARTICLE

The potential of probiotics for treating acne vulgaris: A review

of literature on acne and microbiota

Azadeh Goodarzi1 | Samaneh Mozafarpoor2 | Mohammad Bodaghabadi3 |

Masoumeh Mohamadi1

1
Department of Dermatology, Rasoul Akram
Hospital, Iran University of Medical Sciences
(IUMS), Tehran, Iran
2
Skin Disease and Leishmaniasis Research
Center, Department of Dermatology, Isfahan
University of Medical Sciences, Isfahan, Iran
3
Department of Geriatric, Tehran University of
Medical Sciences (TUMS), Ziaeian Hospital,
Tehran, Iran
Correspondence
Masoumeh Mohamadi, Department of
Dermatology, Rasoul Akram Hospital, Niayesh
Aven., Sattarkhan st., Tehran, Iran.
Email: Mohamadi11248@gmail.com
Abstract
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, pro-
biotics provide health benefits through fighting pathogens and maintaining the
homeostasis of the gut and skin microbiome. The present article reviewed the poten-
tial 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 pro-
biotics, 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 com-
mensal bacterium. The environmental studies showed inhibitory effects of probiotics
on P. acnes, mediating by antibacterial proteins and bacteriocin-like inhibitory sub-
stances, 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 fermen-
tation 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 adju-
vant therapy to conventional modalities for treating mild-to-moderate acne vulgaris.

KEYWORDS

acne vulgaris, microbiome, prebiotics, probiotics, review, synbiotics

1 | I N T RO DU CT I O N reported to be significantly associated with increases in the risks of

insomnia, depression, anxiety, and attention deficit/hyperactivity disor-
As a prevalent disease in adolescents and adults and one of the 10 most der (Silverberg & Silverberg, 2014).The destructive effects of acne on
prevalent disorders in the world, acne affects 47–90% of adolescents quality of life resemble those of certain chronic diseases, including dia-
and the young (Cooper, 1998; Hay et al., 2014; Patel, Bowe, betes and coronary artery diseases. Acne normally affects the patients
Heughebaert, & Shalita, 2010; Perkins, Maglione, Hillebrand, from their school age to adulthood (Cresce, Davis, Huang, & Feldman,
Miyamoto, & Kimball, 2012). The psychological effects of acne were 2014).Given the need for long-term poly-therapies and their side

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https://doi.org/10.1111/dth.13279

2 of 6
effects, which sometimes require changes in treatment regimens, the
patients usually fail to completely adhere to the medications. The bur-
den of medical expenses associated with this prevalent disease has not
been accurately calculated; nevertheless, calculating the work or school
time lost by the patients and their parents and the costs of prescription
medication suggests huge costs are imposed on the healthcare system
and community. Moreover, the patients have difficulties adhering to
these treatments, which are often of a combination type (Anderson,
Dothard, Huang, & Feldman, 2015; Yentzer et al., 2010).The damage
caused by the majority of these treatments to pregnant and
breastfeeding women can also cause treatment interruptions (Awan &
Lu, 2017).Available treatments for acne are limited in type rather than
cost, and these methods have remained unchanged for decades. Pro-
posing modern and safe therapeutic methods with fewer complications
can therefore significantly improve the health status and quality of life
in the patients (Layton et al., 2015).
Topical and oral antibiotics are commonly used to treat acne
(Gollnick et al., 2003; Thiboutot et al., 2009). Antibiotic resistance is,
however, increasing, and resistance to topical macrolides reported in
over 50% of P. acnes strains in many countries has decreased their
effectiveness (Abdel Fattah & Darwish, 2013; Dreno et al., 2014;
Gollnick et al., 2003; Nakase, Nakaminami, Noguchi, Nishijima, &
Sasatsu, 2012; Nast et al., 2012; World Health Organization, 2014).
Moreover, damage to stable skin microbiomes and the antibiotic resis-
tance of nontarget bacteria as a cause of the proliferation of opportu-
nistic pathogens are major concerns, especially in cases of
Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus
(Levy, Huang, Roling, Leyden, & Margolis, 2003; Mills Jr, Thornsberry,
Cardin, Smiles, & Leyden, 2002; Nakase et al., 2014). The global
consensus on improving the treatment outcomes of acne recommends
avoiding the use of topical and oral antibiotics as monotherapies or
poly-therapies (Centers for Disease Control and Prevention, 2013;
Williams, Dellavalle, & Garner, 2012) and supports a combination of a
topical retinoid and a topical antimicrobial, for example, benzoyl perox-
ide (BPO), as the first-line therapy. BPO is recommended to be always
combined with the main medication to treat patients with acne and limit
resistance to oral antibiotics in their long-term administration. The
benefit-to-loss ratio of the long-term consumption of antibiotics should
be carefully evaluated and a single antibiotic be used if possible. To
reduce the risk of antibiotic resistance, effective alternative medications
to antibiotics are required for treating acne (Dreno et al., 2014;
Thiboutot et al., 2009) and (DRÉNO et al., 2004; Eady et al., 1996).
Probiotics are live microorganisms that exert beneficial effects on
the host when adequately consumed, and their excellent characteris-
tics include their safety for the host (Muizzuddin, Maher, Sullivan,
Schnittger, & Mammone, 2012).The wide application range of pro-
biotics, involving the gastrointestinal tract and its functions has been
extensively addressed in literature. Investigating the effects of pro-
biotics on the immune system, skin diseases, diabetes, cancers, liver
diseases, hypertension, the urogenital system, and mouth in addition
to the gastrointestinal tract has yielded promising results (Cencic &
Chingwaru, 2010; Kumar, Mahajan, & Kamra, 2014; Prado, Parada,
Pandey, & Soccol, 2008; Sanders, 2003).
15298019, 2020, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/dth.13279 by Johns Hopkins University, Wiley Online Library on [14/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
GOODARZI ET AL.
Prebiotics defined as “nondigestible food ingredients” widely
affect the host and positively influence their health by stimulating the
growth or activity of one or several bacterial species living in the large
intestine. Symbiotics are defined as products containing both pro-
biotics and prebiotics (Gourbeyre, Denery, & Bodinier, 2011).
The pathophysiology of acne includes hyperseborrhea, follicular
hyperkeratinization, increased propionic colonization by cutibacterium
acnes and inflammation (Al-Ghazzewi & Tester, 2010), which can be
exacerbated by stress. The characteristics of the gastrointestinal tract
can also be altered by stress through accelerating bacterial growth,
increasing the bowel transit time and thus compromising the protec-
tive intestinal barrier (Bowe & Logan, 2011; Volkova, Khalif, &
Kabanova, 2001; Wang & Wu, 2005).Changes in intestinal microflora
have been reported in 54% of patients with acne vulgaris. The high
prevalence of sebaceous gland diseases, including acne, and
significantly-high concentrations of lactobacilli and bifidobacteria in
constipated patients suggest potential relationships between acne
and intestinal microflora (Khalif, Quigley, Konovitch, & Maximova,
2005; Zhang et al., 2008). Most bacteria are probiotic Lactobacilli and
Bifidobacteria, but some other products contains gram positive
Coccobacilli Escherichia coli and yeasts (Mousavi, Mousavi, Razavi,
Emam-Djomeh, & Kiani, 2011).
Probiotics and prebiotics are extensively employed in dermatol-
ogy. Investigating the application of probiotics in treating atopic der-
matitis, acne, eczema, allergies, skin aging, bacterial and fungal
infections and chronic diabetic foot ulcers has yielded promising
results (Fuchs-Tarlovsky, Marquez-Barba, & Sriram, 2016).Given
P. acnes as a major pathogenic agent in acne, probiotics can be effec-
tive in managing acne by controlling the growth of these bacteria. Pro-
biotics can also decrease sebum production, which can reduce
follicular colonization by P. acnes and the associated inflammation
(Kim et al., 2010; Yamamoto, Takenouchi, & Ito, 1995).The decreased
expression of the gene related to the release of inflammatory cyto-
kines, the inhibition of pathogenicCD8 T cells and the activation of
the regulatory T cells can reduce inflammation in acne as a potential
benefit of systemic probiotics (Hacini-Rachinel et al., 2009; Kang
et al., 2009; Muizzuddin et al., 2012). Further research is rec-
ommended that be conducted into the long-term effects of probiotics
on acne lesions given the short-term type of the studies cited.
Researchers have therefore focused on the potential of probiotic
organisms, nonspecific effects on P. acnes, inflammation control, psy-
chiatry, nonpathogenic exploitation with skin-improving effects and
positive effects on the immune system and the gastrointestinal tract.
The present study was conducted to review the effects of probiotics
on treating acne.
2 | METHODS AND MATERIALS
The present review was conducted by searching popular databases,
including Science Direct, PubMed, Scielo, Medline, the National Insti-
tutes of Health, the US National Library of Medicine and the online
database of clinical trials (ClinicalTrials.gov) for scientific articles and

GOODARZI ET AL.
books related to the subject and published by 2019. The keywords
employed included acne, quality of life, treatment, pathophysiology,
skin microbiome, microbiome, probiotic, microbiota, prebiotic, syn-
biotic, and human. Articles reporting irrelevant information were
excluded. The present study evaluated in-vitro studies on probiotics
and their topical and systemic applications.
3 | RESULTS AND DISCUSSION
3.1 | Acne
Acne is a chronic skin disease that is caused by hormone-induced
hyperseborrhea, altered keratinization, immunological and inflamma-
tory processes and the proliferation and accumulation of P. acnes in
hair follicles in the face, neck, chest and back (Degitz, Placzek,
Borelli, & Plewig, 2007).P. acnes is an anaerobic gram-positive bacte-
rium that accumulates and lives in the human skin, especially in
pilosebaceous follicles. Although this bacterium is categorized as sym-
biotic, it can act as an opportunistic pathogen and often cause infec-
tions. The keyrole of this bacterium in inflammatory acne has been
demonstrated (Coenye, Peeters, & Nelis, 2007; Cogen, Nizet, & Gallo,
2008; Nakatsuji et al., 2008). Acne affects 85–90% of populations
aged 12–35 years with a western diet. Some dermatologists consider
this condition a natural evolutionary process. Acne is treated based on
its severity, the patient's type of skin, clinical category, and presence
of skin scars (Haider & Shaw, 2004). The treatments include proper
skincare, topical and oral antimicrobials, retinoids, BPO, and oral con-
traceptives. These methods often used in combination can be re-
adjusted if necessary. The combination type of the treatments and
their side effects, high costs and therapeutic limitations in pregnant
and breast feeding women have resulted in the failure of the existing
therapies (Haider & Shaw, 2004; Leyden, 1997; Narahari, Gustafson, &
Feldman, 2012; Valente Duarte De Sousa, 2019).None of the numer-
ous currently-available treatments are considered a definitive cure for
acne, as they cause major side effects (Mohiuddin, 2019; Valente
Duarte De Sousa, 2019).
3.2 | In-vitro studies
In-vitro studies have detailed the potential of probiotics, including
Streptococcus salivarius and Enterococcus faecalis, for directly inhibiting
the development of acne by producing antibacterial proteins such as
BLIS, which was reported by Bowe et al. to significantly inhibit the
growth of P. acnes. (Bowe, Filip, DiRienzo, Volgina, & Margolis, 2006).
In addition, the immuno modulatory effects of probiotics on
keratinocytes and epithelial cells suggest a physiological mechanism for
supporting their use as an adjuvant therapy for acne. Probiotics have
great positive potential for directly and indirectly treating this disease.
Their direct effects are exerted by inhibiting the growth of P. acnes and
decreasing obvious inflammatory responses and their indirect effects
through reducing the side effects of the existing treatments. These may
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3 of 6
be due to the beneficial effects of these probiotic treatments by using
less-aggressive therapies and positive effects on the recovery of severe
acne disease (Bowe et al., 2006; Kober & Bowe, 2015).
An in-vitro study by Wang et al. found skin microorganisms, espe-
cially S. epidermidis, to ferment glycerol and inhibit the excessive
growth of P. acnes on the culture medium. These skin microorganisms
were isolated from the nasal surface of a subject without acne and
cultured in tryptic soy broth. The bacterial suspension was then com-
bined with the agar melted with and without glycerol and poured onto
Petri dishes. The fingerprint of different subjects was taken by press-
ing their index finger onto the surface of the agar plates. P. acnes inhi-
bition was observed in the genetic analysis of the grown bacterial
colonies, which mostly comprised S. epidermidis. Glycerol fermentation
was also found to play a key role in the inhibitory effect of
S. epidermidis on P. acnes. The presence of S. epidermidis can be there-
fore associated with a natural skin defense against acne, and its
increase by using probiotics can yield better outcomes for the patients
(Wang et al., 2014).
As part of the bacteria in the oropharyngeal system, S. salivarius
was found to inhibit the growth of P. acnes in-vitro through producing
BLIS. This study was conducted on 106 healthy subjects by collecting
swabs from the dorsal surface of their tongue and performing dilution
and inoculation onmitis-salviarius agar. BLIS production was evaluated
using a modified version of deferred antagonism assays. Topical for-
mulations containing BLIS or BLIS-producing bacteria were also pro-
posed for treating acne vulgaris (Bowe et al., 2006).
These probiotic bacteria inhibited the proinflammatory cytokine
interleukin-8 in epithelial cells and keratinocytes, which induces an
immunoregulatory function. This effect can be explained by the fact
that these microorganisms do not cause proinflammatory stimulation;
rather, they trigger anti-inflammatory actions and regulate the genes
associated with epithelial adhesion molecules and homeostasis. The
inhibitors produced by bacteria significantly inhibit the growth of
other bacteria without damaging the skin microbiome. Their benefits
therefore resemble those of antibiotics in case their major side effects
are avoided. As immunoregulators, probiotics can be more effective
especially in treating Grade III and IV acne, which cause more severe
inflammation (Cosseau et al., 2008).
An in-vitro study by Oh et al. demonstrated the inhibitory effects
of bacteriocin produced by Lactobacillus species HY499 on inflamma-
tory and pathogenic bacteria in the skin such as S. epidermidis, Staphy-
lococcus aureus, S. pyogenes, and P. acnes. Despite inhibiting the
growth of these bacteria on the culture medium, bacteriocin exerted
no inhibitory effects on the growth and proliferation of fibroblasts. In
addition, the human patch test showed no allergicreactions and irrita-
tion as a result of using bacteriocin. The authors recommended using
bacteriocin produced by Lactococcus sp. HY499 as an antimicrobial in
cosmetic formulations. Causing no allergic reactions and irritation con-
stitutes a significant potential advantage of probiotics compared to
that of the existing treatments (Oh et al., 2006).
Gueniche et al. found Lactobacillus paracasei CNCM I-2116
(ST11) to inhibit P-substance-induced skin inflammation and acceler-
ate the regeneration and return of skin barrier function. They also

4 of 6
found ST11 to significantly eliminate all the effects of P-substance,
including vasodilatation, edema, mast cell degranulation and TNF-α
release, compared to in the controls. Moreover, the ST11-associated
skin barrier recovery was found to be accelerated in an ex-vivo skin
culture. This advantage was found to be particularly useful for coun-
teracting the side effects of conventional treatments containing free
radicals (Gueniche et al., 2010).
3.3 | In-vivo studies on topical probiotics
Kang et al. (2009) examined the effect of a lotion on P. acnes. This
lotion contained Enterococcus faecalis SL-5 as a species of Lactobacil-
lus genus extracted from human feces. These species exert the most
significant effects on gram-positive bacteria, especially P. acnes. These
bacteria were isolated as a bacteriocin from the feces of a healthy
Korean adult and grown in an optimal medium. An aqueous lotion was
prepared by deriving a thick powder from a sterilized culture medium.
The same lotion free from the CBT SL-5 powder was considered pla-
cebo. A two-stage 8-week randomized trial was conducted in Phase III.
Seventy patients over the age of 12 years with mild-to-moderate acne
vulgaris were assigned to the CBT SL-5 group and the placebo group.
The patients were instructed to apply the lotion on their affected areas
twice a day. Evaluations were performed at baseline and 2, 4, and
8 weeks later. The significant reduction observed in the inflammatory
lesions in the treatment group suggested the CBT SL-5 lotion inhibited
P. acnes and reduced the production of inflammatory mediators synthe-
sized and released by this pathogen (Kang et al., 2009).
A clinical trial by Muizzuddin et al. reported reductions in mild
acne lesions and erythema as well as increases in skin barrier recovery
using Lactobacillus plantarum. The extract was produced after grow-
ing Lactobacillus in a previously-sterilized culture medium for
18–24 hr. Firstly the solution was filtered through a 0.45-l filter and
then through a 0.22-l filter. The aqueous lotion was ultimately pre-
pared at 1 and 5% concentrations of probiotics. The lesions were eval-
uated after treating 10 volunteers aged 18–50 years with the
formulation once a day for 4 days. The formulation with a 5% concen-
tration of the bacteria significantly reduced the lesion size and ery-
thema, whereas the formulation with a 1% concentration exerted no
significant effects. This study recommended using the formulation
with a 5% concentration of Lactobacillus plantarum for treating mild
acne lesions. The ineffectiveness of the extract with a 1% concentra-
tion also suggested the dose-dependent effect of lactobacilli
(Muizzuddin et al., 2012).
3.4 | Interventional studies
In 1930, stokes and Pillsbury explained that acidophilus bacteria of
milk could work as medication with inhibitory effect on brain-gut-skin
inflammatory process; meanwhile, other physicians cited the popular-
ity of the culture of using milk for treating acne among the general
public (Ereaux, 1938).
15298019, 2020, 3, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/dth.13279 by Johns Hopkins University, Wiley Online Library on [14/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
GOODARZI ET AL.
The effectiveness of probiotics has rarely been addressed in litera-
ture. The first series of official clinical profiles reported about the
potential value of probiotic Lactobacillus was published in 1961. Robert
H. Sawyer, a physician in Union Memorial Hospital in Baltimore, the
US, followed up 300 patients who consumed commercial probiotics,
that is, Lactinex® tablets comprising a mixture of L. acidophilus and
L. bulgaricus. He used a supplementary probiotic protocol for 8 days,
performed a 2-week wash out and then re-administered the treatment
for another 8 days (the reasons for selecting this regimen and dose are
unknown). He observed some degrees of clinical improvement in 80%
of the patients with acne and found this intervention to be more valu-
able in cases of inflammatory acne. Interactions were also observed
between the skin manifestations of acne vulgaris and the metabolic
processes of the gastrointestinal tract without investigating a control or
placebo group (Siver, 1961).
In Italy, clinical responses, lesion repair and better tolerance to oral
antibiotics were reported in 20 patients receiving oral probiotic supple-
ments containing 250 mg of freeze-dried L. acidophilus and
bifidobacterium bifidum as an adjuvant therapy to the systemic treat-
ment compared to in the other 20 patients (Marchetti, Capizzi, &
Tulli, 1987).
Similarly, investigating the attenuation of bacterial microflorain
Russian acne patients showed faster improvements in clinical symp-
toms in the patients who received correcting agents of the intestinal
microflorain addition to conventional medications for acne (Volkova
et al., 2001).
Jung et al. randomly assigned45 female patients aged 18–25 years
to a group that only received probiotics, a group that received pro-
biotics and minocycline and a group that only received minocycline.
The total number of lesions significantly decreased in all the patients
after 4 weeks, and the improvement continued duringa12-week
follow-up. A significant decrease was observed in the total number of
lesions in the group receiving probiotics and minocycline compared to
in the other two groups, whereas the group receiving minocycline alone
developed candidal vaginitis (Jung, Tse, Guiha, & Rao, 2013).
A study by Kim et al. on 36 acne patients showed that consuming
a fermented dairy drink containing lactobacillus improves the clinical
dimensions of acne within 12 weeks. Using the probiotic drink signifi-
cantly decreased the total number of lesions through significantly
reducing sebum production. Although adding lactoferrin as an anti-
inflammatory milk protein to the probiotic drink increased the effec-
tiveness in reducing inflammatory lesions, the exclusive benefits of
the probiotic drink suggest that probiotics can be used as an adjunct
therapy for acne (Kim et al., 2010).
Acne is the most common dermatologic disorder with a wide and
extensive target population. Due to chronic and long lasting disease
period and many individualized treatment related concerns and con-
traindication, nowadays there are many efforts to find out and control
acne associated factors that affect its incidence and severity also ther-
apeutically manage acne with better efficacy and higher safety profile,
like using probiotics as we discussed in this review, or even use of
nonmedical treatments. (Goodarzi, n.d.; Behrangi et al., 2019;
Lajevardi et al., 2014; Mehran et al., 2019).

GOODARZI ET AL.
4 | C O N CL U S I O N
Numerous in-vitro and in-vivo studies suggest that probiotics as an
adjunct therapy comprising either topical or oral products can play an
effective role in managing acne by directly preventing the growth of
opportunistic bacteria or by controlling inflammation. Interventional
studies are recommended to be conducted using large samples and long
follow-ups to demonstrate the effectiveness of these beneficial bacteria
and pinpoint their other potential advantages and disadvantages.
ACKNOWLEDGMENT
This study was supported by a research grant from Tehran University
of Medical Sciences, Tehran, Iran. Also, the authors would like to
thank Rasoul Akram Hospital Clinical Research Development Center
(RCRDC) for its technical and editorial assist.
ORCID
Azadeh Goodarzi https://orcid.org/0000-0002-1249-4429
Masoumeh Mohamadi https://orcid.org/0000-0002-5167-5230
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How to cite this article: Goodarzi A, Mozafarpoor S,
Bodaghabadi M, Mohamadi M. The potential of probiotics for
treating acne vulgaris: A review of literature on acne and
microbiota. Dermatologic Therapy. 2020;33:e13279. https://
doi.org/10.1111/dth.13279