Am J Clin Dermatol

DOI 10.1007/s40257-017-0300-2

SYSTEMATIC REVIEW

Probiotics, Prebiotics, and Synbiotics for the Treatment

and Prevention of Adult Dermatological Diseases
Manisha Notay1 • Negar Foolad1 • Alexandra R. Vaughn1,2 • Raja K. Sivamani1,3

Ó Springer International Publishing Switzerland 2017

Abstract shown to improve inflammatory markers, and one study

Background Probiotic, prebiotic, and synbiotic supple- suggested that probiotics could be used as adjunctive
mentation is becoming more prevalent nowadays. Clinical therapy in the treatment of acne.
studies have demonstrated some of the medical benefits of Conclusion Preliminary studies are optimistic for the use
probiotics, prebiotics, and synbiotics within dermatology of some strains of probiotics for symptomatic and clinical
but an evidence-based review of their effects in adults is improvement in AD, and as adjunctive treatment with
needed. antibiotics for acne. Further research is necessary to better
Objective The aim of this study was to identify evidence assess how probiotics and prebiotics may be used within
for the use of supplementation with probiotics, prebiotics, dermatology.
or synbiotics for the prevention and treatment of derma-
tological diseases in adults.
Data sources We conducted a search of the Ovid MED-
Key Points
LINE, Cochrane Central Register of Controlled trials and
EMBASE electronic databases from 1 January 1946 to 11
Probiotics may be useful in the treatment of adults
January 2017.
with atopic dermatitis and acne.
Study selection Trials examining supplementation in the
treatment of dermatological diseases using oral or topical The mechanism of action remains unclear but is
probiotics, synbiotics, and prebiotics in adults over the age thought to be due to the alteration of the gut
of 18 years were selected. microbiome and modulation of the immune system.
Data extraction Of 315 articles, 12 met the inclusion More studies of probiotics and prebiotics for the skin
criteria. are warranted.
Data synthesis Nutritional supplementation with probi-
otics and prebiotics was shown to improve atopic der-
matitis (AD) symptomatology, quality of life, or clinical
severity in six of nine studies. One study in psoriasis was
1 Introduction

& Raja K. Sivamani Probiotics are live microorganisms that can confer health
raja.sivamani.md@gmail.com benefits when administered in adequate doses [1]. The most
1
Department of Dermatology, UC Davis, 3301 C Street, Suite
commonly used microorganisms are Lactobacillus, Bifi-
1400, Sacramento, CA 95816, USA dobacterium, Enterococcus, Pronionibacterium, and some
2
Drexel University College of Medicine, Philadelphia PA,
yeasts such as Saccharomyces boulardii. Their health
USA benefits include the prevention of antibiotic-associated
3
Department of Biological Sciences, California State
diarrhea, treatment of irritable bowel syndrome, and
University – Sacramento, Sacramento, CA, USA inflammatory bowel disease [2].
 M. Notay et al.

Prebiotics are ingredients and substances that can pro- dermatological condition. Studies that reported the treat-
mote the growth of certain bacteria in the gut. It is believed ment or prevention of dermatological diseases were
that an ingredient must possess three key features to be selected. Publications were excluded if infants, children, or
considered a prebiotic. First, it should resist breakdown by adolescents were included.
mammalian enzymes and gastrointestinal absorption; sec-
ond, it must be fermented by the microbiotia of the intes- 2.2 Study Selection and Data Extraction
tine; and, last, it must be able to selectively stimulate the
growth and/or activity of the intestinal bacteria, which have On the basis of our selection criteria, all authors (MN, NF,
been associated with improving human health [3]. Prebi- ARV, and RKS) independently reviewed all eligible stud-
otics usually target the activity of Lactobacillus and Bifi- ies and the final 12 full-text articles, and resolved any
dobacterium [4]. differences by consensus. For each study, the following
Synbiotics are composed of a combination of prebiotics information was abstracted and is documented in Tables 1
and probiotics. The prebiotic component is thought to assist and 2: (1) skin disease, (2) number of subjects, (3) study
with the implantation and survival of live microbial dietary design, (4) probiotic intervention, (5) intervention dosage,
supplements. Specifically, the prebiotic component must (6) primary outcome measures, and (7) major results. A
selectively favor the probiotic organisms in the formulation total of 420 patients were included in these 12 studies
[5]. (Fig. 1).
There is a growing body of research involving the use of
prebiotics, probiotics, and synbiotics in pediatric atopic 2.3 Quality of Included Studies
dermatitis (AD). Research suggests pre- or probiotics may
be beneficial in the prevention and amelioration of AD [6], Study quality was assessed independently using the Jadad
which is thought to be due to the alteration of the intestinal score for analyzing randomized controlled trials (RCTs)
microbiome and modulation of the immune system. Fewer [8]; the Jadad score establishes the methodological quality
studies exist regarding the use of prebiotics and probiotics of studies based on a 5-point scale according to repro-
in adults with dermatological diseases, and we sought to ducibility and appropriateness of randomization, blinding,
investigate and review the current clinical evidence [7]. and the fate of subjects. Using this system, the quality of a
trial is categorized as ‘high’ (Jadad score 3–5) or ‘low’
(Jadad score 0–2) [8].
2 Methods

We conducted a search of the Ovid MEDLINE, Cochrane 3 Results

Central Register of Controlled Trials, and EMBASE elec-
tronic databases for articles published from 1 January 1946 3.1 Atopic Dermatitis
to 11 January 2017. For Ovid MEDLINE, we used the
search terms ‘probiotics’, ‘prebiotics’, ‘synbiotics’, ‘skin Nine studies assessed the impact of probiotics in adults
diseases’, ‘humans’ and ‘clinical trial. The following with AD [1], and no studies were identified in adults for the
Medical Subject Heading (MeSH) terms were combined treatment of AD with prebiotics or synbiotics.
using the ‘AND’ Boolean operator to find relevant studies
in the Cochrane Central Register of Controlled Trials: ‘skin 3.1.1 Bifidobacterium
diseases’, ‘probiotics’, ‘prebiotics’, and ‘synbiotics’.
Additionally, the following search terms were used in One randomized, double-blind, placebo-controlled study
EMBASE for relevant studies: ‘skin’, ‘diseases’, ‘probiotic using Bifidobacterium animalis (subsp. lactis LKM512)
agent’, ‘prebiotic agent’, ‘synbiotic agent’, ‘clinical trial’, found that subjects in the probiotic group experienced a
and ‘humans’. Our searches were limited to articles that significant improvement in itch after 8 weeks [9]. This
tested probiotics, prebiotics, or synbiotics among adults group also experienced an improvement in the dermatol-
only. Furthermore, we searched through the references of ogy-specific quality-of-life (QoL) questionnaires. The
the chosen articles for additional studies. researchers followed the severity of AD utilizing a 5-point
scale and found that while probiotic supplementation
2.1 Inclusion and Exclusion Criteria improved clinical severity compared with baseline, there
was no significant difference in severity scores between
We included clinical trials and cohort studies that exam- groups. Researchers found an increase in the anti-noci-
ined the effect of probiotics, prebiotics, or synbiotics ceptive metabolite kynurenic acid (KYNA) in three
among adults 18 years of age and older with a patients whose itch improved after the administration of
Table 1 Human clinical trials of probiotics, prebiotics, and synbiotics for the treatment of atopic dermatitis in adults
Skin Study No. of subjects Study design Intervention Dosage Control or Primary outcome Results Study limitations Jadad
condition and duration placebo measures score
(RCT)

AD Matsumoto 44 8-week, rand, Capsules containing B. 6 9 109 CFU B. Placebo capsule Severity grading of NS difference in severity 5
et al. [9] Male and female db, pc, animalis (subsp. lactis animalis subsp. containing AD (5-point of AD or VAS scores
Japanese adults parallel- LKM512) lactis LKM512 per skim milk, scale based on between groups.
with moderate or group capsule (capsule also glucose, clinical Severity scores of AD
severe AD, mean comparative contained skim milk, inulin, dextrin, assessment) group did improve
age 33–34 years study glucose, inulin, and silicon Itch grading during compared with baseline
(age cut-off not dextrin, and silicon dioxide the day and at in the probiotic group
specified) dioxide) night (VAS Improvement in itch and
score) QoL scores in probiotic
QoL questionnaire group only

Fecal microbiome SS higher fecal

analysis using populations of
RT-PCR and Atopobium and
T-RFLP LKM512 in the
probiotic group
Fecal KYNA compared with placebo
concentrations
KYNA concentration
significantly increased
in feces of the probiotic
group compared with
the placebo group
AD Matsumoto 10 12 weeks LKM512 yogurt: B. 5.2 9 107 CFU/g Yogurt Subjective Improvement in itch and Small sample size
Probiotics, Prebiotics, and Synbiotics for Adult Dermatological Diseases

et al. [10] Adult males and (4 weeks animalis (subsp. lactis B. animalis (subsp. fermented symptoms (‘itch’ burning in 4/10 and 3/8 All subjects enrolled had
females treatment LKM512), lactis LKM512) with L. and ‘burning’) with LKM512 yogurt been previously
diagnosed with yogurt, Lactobacillus delbrucckii Fecal short chain consumption. undergoing long-term
4 weeks delbrucckii (subsp 4.7 9 108 CFU/g (subsp. Improvement in itch and
moderate AD fatty acids Kampo treatment,
(average age washout, bulgarius KLM1759), the lactic acid bacteria bulgaricus burning in 1/10 and 2/8 therefore all changes
4 weeks and Streptococcus LKM1759) Serum cytokines subjects in placebo
22.1 years, age Dose: 100 g/day of (IL-4, IL-5, IL- cannot be solely
cut-off not placebo thermophiles yogurt per individual and S. groups attributable to LKM512
yogurt) LKM1742 thermophiles 10, IL-12, IFNc)
specified) NS increase in acetate, yogurt consumption
db, rand, pc LKM1742 propionate, butyrate,
crossover and isobutyrate after
study LKM512 yogurt
SS increase in IFNc in the
LKM512 group
AD Yoshida 24 8-week, rand, Test capsules filled with 2.0 9 1010 CFU per Placebo capsules AD severity using SS decrease in the The overall symptoms of 2
et al. [12] Adult patients db, pc study lyophilized powder of capsule, subjects (contents SCORAD objective SCORAD of disease severity were
(aged live Bifidobacterium took two capsules unspecified) Serum IgE, the probiotic group. NS lower in the placebo
20–65 years) breve (strain YY) per day eosinophils, and change in SCORAD in group than the treatment
diagnosed with plasma TARC the placebo group group at baseline
AD QoL questionnaire NS change in serum IgE, Small subject number
plasma TARC, or serum
eosinophils in either
group
SS decrease in QoL score
in the probiotic group,
but NS change in the
placebo group
Table 1 continued
Skin Study No. of subjects Study design Intervention Dosage Control or Primary outcome Results Study limitations Jadad
condition and duration placebo measures score
(RCT)

AD Drago et al. 38 16-week, rand, Sachets containing 1 9 109 CFU/g in Maltodextrin AD severity using SS decrease in SCORAD 5
[14] Males and females, db, pc study freeze-dried L. maltodextrin, twice alone, twice SCORAD score only in the
aged salivarius LS01 daily daily DLQI probiotic group
18–46 years, questionnaire DLQI score progressively
with Serum IgE decreased, with
moderate/severe maximum decrease at
AD Quantification of week 8 in the probiotic
fecal bacteria group only
NS change in serum IgE
in either group
SS decrease in fecal
staphylococci in the
probiotic group,
persisting even 1 month
after treatment ended
AD Kaur et al. 16 12-week, rand, Goat milk fermented 200 mg/day containing Control group AD severity using NS decrease in SCORAD Limited subject number 2
[15] Healthy male and open with L. fermentum 3 9 109 CFU/ml did not receive SCORAD index in treatment and No blinding, thus
female comparative (ME-3) probiotic drink Skin iron level control groups increasing the risk for
volunteers with study SS decrease in skin iron bias
Total glutathione
mild-to-moderate and GSSG of from 300 to 100 umol/g
AD aged skin and blood in the probiotic group
20–42 years SS decrease in GSSG in
Oxidized LDL
the probiotic group
Serum TAC and
TAA Oxidized LDL SS
decreased in the
probiotic group
compared with the
control group
SS increase in TAC and
TAA in the probiotic
group compared with
the control group
AD Moroi et al. 34 12-week, Heat-killed L. paracasei 100 mg (*2 9 1011) 500 mg dextrin 5-point skin SS decrease in skin Use of topical medications 5
[16] Male and female prospective, K71 heat-killed L. and 0.45 mg severity score severity scores in the during the study could
Japanese adults, rand, db, pc, paracasei and carotene (0 = no L. paracasei group confound the results
aged 20–65 years parallel- 400 mg dextrin (dissolved in symptom, compared with placebo
with mild to group NSD300 (dissolved water, coffee, 1 = mild, (p \ 0.01)
moderate AD comparative in water, coffee, or or tea) 2 = moderate, No change in itch or QoL
tea) 3 = severe, scores in either group
4 = extremely
severe) No AE reported

Itch scores VAS at

daytime and
night
QoL questionnaire
AE
M. Notay et al.
Table 1 continued
Skin Study No. of subjects Study design Intervention Dosage Control or Primary outcome Results Study limitations Jadad
condition and duration placebo measures score
(RCT)

AD Iemoli et al. 48 12-week, db, Freeze-dried mixture of 1 9 109 CFU/g each Placebo: AD severity using SS decrease in SCORAD Low patient number 5
[18] Males and females rand, pc L. salivarius LS01 bacterial stain in maltrodextrin, SCORAD index in the probiotic Higher number of patients
with AD, aged study DSM 2275 and B. maltrodextrin, twice twice daily DLQI group only after with respiratory allergy
30–35 years breve BR03 DSM daily (freeze-dried questionnaire 12 weeks in the probiotic group
16604 powder) SS decrease in DLQI in (could explain elevated
Gut permeability
barrier (plasma the probiotic group only LPS)
LPS) after 12 weeks

Immunologic Plasma LPS was SS

parameters higher in the control
(peripheral blood group than the treatment
mononuclear group at the end of
cells, activated treatment
CD8? T cells, Activated CD8? T cells
Th1, Th2, Th17 decreased throughout
and Treg cells) treatment in the
probiotic group
SS increase in
unstimulated Tregs in
the probiotic group
Probiotic-induced SS
increase in Th1 cells
and decrease in Th2 and
Probiotics, Prebiotics, and Synbiotics for Adult Dermatological Diseases

Th17 cells
SS decrease in
staphylococci in the
probiotic group
compared with placebo
AD Roessler 30 8-week 9 2 Probiotic yoghurt drink 100 mL twice daily Placebo drink: AD severity using The SCORAD in AD 5
et al. [19] 15 healthy patients db, pc, rand containing S. identical SCORAD group decreased by
(mean age crossover thermophilus, L. composition as Major leukocyte 15.5%, but NS
24 ± 3 years) study paracasei LPC-37, L. treatment subset SS increase in CD57? in
and 15 people acidophilus 74-2, and drink, but phenotypes of healthy subjects after
with AD (mean B. animalis subsp. without the blood probiotic
age lactis DGCC420 probiotic supplementation, but
strains Phagocytic and
23 ± 3 years) oxidative burst not in the AD group. SS
[age cutoff not activity of decrease in
specified] granulocytes and CD4?CD54? in AD
monocytes patients, only
No difference in
CD4?CD25? T cells
between groups
SS increase in phagocytic
activity of granulocytes
and monocytes in
healthy subjects after
probiotic treatment
 M. Notay et al.

AD Atopic dermatitis, AE adverse event, CFU colony forming unit, db double-blind, DLQI Dermatology Life Quality Index, GSSG oxidized glutathione, Ig immunoglobulin, IL interleukin, IFN interferon, KYNA kynurenic acid, LDL
(RCT)

low-density lipoprotein, LPS lipopolysaccharide, NS not statistically significant, pc placebo-controlled, QoL quality of life, Rand randomized, RCT randomized controlled trial, RT-PCR real-time polymerase chain reaction, SCORAD
SCORing Atopic Dermatitis, SS statistically significant, Th T helper, Treg T regulatory, TAC/TAA total antioxidant capacity/total antioxidant ability, TARC thymus and activation-regulated chemokine, T-RFLP terminal restriction
LKM512 [9]. It was postulated that this improvement was
Jadad
score
due to KYNA production in the intestines; therefore, this

3
could be a potential treatment for AD-associated pruritus

probiotic discontinuation
corticosteroids and other

other published clinical

shorter compared with

No follow-up data after

Duration of study (only
[9].

medications was not

30 days) was much

recorded, therefore
Additionally, a prior 8-week crossover trial found that

results could be
Study limitations

patients taking B. animalis (subsp. lactis LKM512) expe-

Use of topical

confounded
rienced moderate improvement in the symptoms of itch and

studies
burning when compared with placebo [10]. All patients
enrolled had been previously treated with long-term
No change in fecal counts

Kampo medicine (the practice of Chinese herbal medicine

group and no change in

probiotic group had NS

SS decrease in SCORAD
index in the probiotic

probiotic and placebo

of clostridia between

in Japan), which could make it difficult to differentiate

decrease in fecal S.
the placebo group

10 of 13 patients in

between the effects of Kampo medication and the effects of

B. animalis. A statistically significant increase in interferon
groups

aureus

(IFN)-c was observed in both groups, however the increase

Results

was greater in the probiotic group [10]. The authors of the

study did not suggest an explanation for this; however,
clostridium using
DNA sequencing
AD severity using

Fecal counts of S.

studies in children have shown an increase in IFNc after

Primary outcome

the administration of probiotics. It has been postulated that

aureus and
SCORAD

this is a reflection of an increased T helper (Th)1 response

measures

[11], although the significance of this is not clear.

In a study by Yoshida et al. [12], Bifidobacterium breve
(strain YY) was administered to adults with AD over an
maltodextrin

8-week period. Compared with controls, the probiotic

Gluten-free
Control or
placebo

group (n = 16) demonstrated a decline in the SCORAD

(SCORing Atopic Dermatitis) index after 8 weeks [12];
however, the only parameter of the SCORAD index that
2 9 109 CFU/sachet
of S. thermophilus
5 9 109 CFU/sachet

showed a statistically significant decline was the intensity

of L. salivarius

criteria (8.0 ± 2.9–6.8 ± 3.0; p = 0.018). There was a

statistically significant reduction in the objective SCORAD
Dosage

(33.7 ± 13.6–23.8 ± 4.0; p = 0.034), which consisted of

the extent and intensity parameters but excluded subjective
symptoms. Furthermore, there was a statistically significant
freeze-dried mixture of

LS01DSM 22775 and

S. thermophiles ST10

decline in the QoL ‘Skindex-29-J’ scores (a questionnaire

Sachets containing

that assesses symptoms, functioning, and emotions in AD

L. salivarius

DSM 25246

patients over the previous 4 weeks [13]) in the probiotic

Intervention

group (p = 0.019) compared with baseline. In the study,

subjects were not randomized according to disease sever-
ity, and subjects with higher disease severity were found in
prospective,

the probiotic arm of the study. The average total baseline

Study design
and duration

controlled
pilot trial

SCORAD scores for the probiotic and placebo groups were

30-day,

fragment length polymorphism, VAS visual analog scale

41.0 and 25.7, respectively (p = 0.027). This may have

unevenly affected the ability of each treatment group to
aged 25–63 years
Males and females,

improve. In the study, stool samples demonstrated the

No. of subjects

probiotic was able to colonize the gastrointestinal (GI) tract

with AD

as there was an increase in the colonization rate of the gut

microbiome with Bifidobacteria [12].
25

3.1.2 Lactobacillus
Drago et al.
Table 1 continued

[20]
Study

Researchers studied the effects of Lactobacillus salivarius

LS01 for 16 weeks in adults with AD [14] and noted a
condition

significant reduction in the SCORAD and Dermatology

Skin

AD

Life Quality Index (DLQI) ratings in the probiotic-treated

Probiotics, Prebiotics, and Synbiotics for Adult Dermatological Diseases

group (week 0: 27.6 ± 3.4 vs. week 16: 13.1 ± 0.3; paracesi LPC-37, Lactobacillus acidophilus 74-2, and Bi-
p \ 0.001). Moreover, there was a statistically significant fidobaterium animalis subsp. lactis DGCC 420 was
decline in Th1 and Th2 cytokines compared with baseline administered to adults with and without AD [19]. After
in the placebo group only (T0: 28.2 ± 2.5 pg/ml vs. T16: 8 weeks of probiotics among patients with AD, a non-
33.0 ± 3.3). The staphylococcal load in the fecal micro- significant decrease in the SCORAD was observed (from
biome in the probiotic-treated group was reduced [14]. -15.5 to -20.3%; p = 0.081). Researchers did not
One study used Lactobacillus fermentum (ME-3) over a observe a statistically significant decline in immunoglob-
3-month period in 10 patients with AD compared to another ulin (Ig) E levels in AD patients after administration of
group that did not receive a probiotic [15]. Patients in both probiotics [19].
groups experienced a non-significant improvement in their Drago et al. [20] investigated the effect of adding tara
SCORAD index. Among the probiotic-treated group, a sig- gum and Streptococcus thermophilus ST10 DSM 25246 to
nificant reduction was seen in skin iron levels, diene conju- L. salivarus LS01 DSM 22775 [20]. Tara gum is thought to
gate (DC) levels, and glutathione redox ratios, which are all act as a gelling complex, which would adhere to the
markers of oxidative stress. In addition, there was a statis- intestinal mucus and improve barrier function, thereby
tically significant decline in blood markers of oxidative improving the activity of L salivarus. Twenty-five AD
stress, such as oxidatively modified low-density lipoprotein patients were included and were randomized to receive
(oxLDL). This demonstrated that AD patients could be at either a placebo or probiotic. A statistically significant
higher oxidative burden, which may be reduced by the improvement in the SCORAD index was observed after
administration of a probiotic [15]. The significance of the administration of the probiotic (p \ 0.0001). Staphylo-
reduction in oxidative stress is not clear since there was no coccus aureus is reportedly found more frequently in the
difference in the improvement of the SCORAD index. gut microbiome of subjects with AD [21]. Although there
In another study, 34 subjects with AD were administered was a trend toward a decrease in the S. aureus load in the
placebo or probiotic Lactobacillus paracasei K71 fora fecal microflora of the probiotic group, this decrease was
period of 12 weeks [16]. Skin severity scores (based on not statistically significant (p = 0.08) [20]. Without a fol-
eruption intensity and area of involvement developed by low-up study after the supplementation ceased, it cannot be
the Japanese Dermatological Association [17]) in the pro- ascertained whether L. salivarus persisted in the gut after
biotic group were decreased from baseline, at week 8 treatment ended.
(p \ 0.05), and at week 12 (p \ 0.01). There was no
influence of probiotic use on the QoL or itch scoring. 3.2 Acne
Subsequently, the placebo group had a 1.9-fold greater use
in topical therapeutics in the placebo group; however, this Acne vulgaris is one of the most common chronic derma-
difference was not statistically significant [16]. tological conditions affecting both adolescents and adults
[22]. Only one study was found regarding the role of
3.1.3 Probiotic Mixtures probiotics in the treatment of acne. In a prospective, ran-
domized, open-label study, 45 female patients aged
Researchers conducted an RCT using a combination of 18–35 years with mild to moderate acne vulgaris were
probiotics containing Lactobacillus salivarius LS01 DSM enrolled into three groups: probiotic supplementation,
2275 and Bifidobacterium breve BR03 DSM 16604 [18]. minocycline, and treatment with both probiotics and
Subjects using probiotics had a significant improvement in minocycline. The probiotic was a mixture of Lactobacillus
clinical scores (SCORAD and DLQI). The researchers also acidophilus (NAS super-strain), Lactobacillus delbrueckii
observed a reduction in plasma lipopolysaccharide (LPS) subspecies bulgaricus (LB-51 super-strain), and Bifi-
in the probiotic group. Plasma LPS is a marker of inflam- dobacterium bifidum (Malyoth super-strain). The treatment
mation and permeability of the intestinal endothelium. It is period lasted a total of 12 weeks and lesion counts were
thought that altered gut permeability leads to toll-like assessed throughout this time. A total of 43 subjects
receptor (TLR)-dependent immune activation. They completed the study.
demonstrated a reduction in CD8/CD38/CD45RO T cell By week 4, all groups had a significant improvement in
activation in the probiotic group, which is thought to be a total lesion count, with no significant differences between
marker of immune activation. After treatment with a pro- groups. Similarly, at the 8-week mark, all groups continued
biotic, it was found that there was a significant decrease in to have a significant improvement in total lesion count
the staphylococcal load of the feces [18]. (p = 0.001, probiotic only; p \ 0.001, remaining groups).
In the double-blinded, placebo-controlled, randomized The trend continued at week 12 for all three groups. By
crossover study by Roessler et al. [19], a probiotic drink weeks 8 and 12, the group receiving both probiotics and
composed of Streptococcus thermophiles, Lactobacillus minocycline had a significantly lower total lesion count
 M. Notay et al.

compared with those taking probiotics only or minocycline were recruited and assigned to receive either placebo or
only. All three groups had a significant improvement in probiotic for 8 weeks. Baseline plasma C-reactive protein
non-inflamed lesion count at weeks 4, 8, and 12. At weeks (CRP), tumor necrosis factor (TNF)-a and interleukin (IL)-
4, 8, and 12, subjects who were in the probiotic-only group 6 levels were elevated in psoriasis subjects comparison
had a greater decrease in non-inflamed lesion count com- with healthy controls. CRP declined significantly after
pared with those in the minocycline-only group. Future 8 weeks of therapy compared with placebo (p = 0.0425)
studies should assess how probiotics affect sebaceous gland and compared with baseline (p = 0.0161), and TNFa
function and sebum composition. With regard to the declined significantly after 8 weeks of therapy compared
inflamed lesion count, subjects who took either probiotics with baseline (p = 0.0269) and placebo (p = 0.0405).
or minocycline achieved an improvement by week 8, and Researchers did not observe any changes in IL-6 levels in
continued to improve significantly by week 12 compared subjects with psoriasis treated with probiotics for 8 weeks
with baseline. The group that received both probiotics and compared with control subjects. When performing a com-
minocycline experienced a significant reduction as early as bined analysis of all three inflammatory markers (IL-6,
week 4, and continued to improve significantly more TNFa, and CRP), there was a decrease in the combined
compared with the other groups. analysis in 75% of those receiving probiotics compared
Thirteen percent of patients in the minocycline-only with 7% in the group receiving placebo. It is unclear how
group experienced vaginal candidiasis. No cases were the combined analysis offers more insight over the indi-
reported in the group that received both probiotics and vidual analyses of IL-6, TNFa, and CRP. Interestingly,
minocycline, which suggests that probiotics may help these three parameters remained unaffected in the healthy
suppress the growth of unwanted microorganisms in the control group after treatment with B. infantis 35624. In this
vaginal tract [22]. More studies are needed to evaluate the study, it is unclear if the biochemical improvements were
effects of probiotics on acne treatment, specifically whether accompanied by clinical improvements as no grading of
it is efficacious as a stand-alone treatment or an adjunctive disease severity was performed after baseline. These results
therapy. suggest that B. infantis 35624 is able to reduce proin-
flammatory biomarkers in a systemic inflammatory disor-
3.3 Wound Healing der [24]; however, future studies should incorporate
clinical grading and assessments.
Acute wounds and non-healing chronic wounds are a
common occurrence in dermatology. Peral et al. evaluated
the role of probiotics in wound healing of burn injuries 4 Quality Assessment and Risk of Bias
[23]. Eighty patients with second- or third-degree burns
were randomized to receive topical wound treatment with 4.1 Study Qualities from the 12 Studies Analyzed
either Lactobacillus plantarum (strain not reported) or (Tables 1 and 2)
standard silver sulphadiazine (SD-Ag). Treatment with L.
plantarum was found to have similar effects as SD-Ag to The majority of studies randomized and blinded subjects to
promote complete healing of second-degree and early treatment; however, not all studies were blinded, leading to
third-degree burn wounds. In late third-degree burn a risk of bias. For certain disease states such as acne,
wounds (3–7 days post-burn), L. plantarum application psoriasis, and wound healing, only one study was identified
lead to a statistically significant 17% increase in complete (Table 2), therefore, no conclusions can be drawn.
healing compared with wounds that had SD-Ag applied. Of the nine studies investigating probiotic use in AD
Due to the low number of subjects in each group, (Table 1), seven used SCORAD as one of their primary
researchers were not able to find whether the results were outcome measures. Two of the three remaining studies did
significant. Additional studies with a larger sample size are not use SCORAD, but instead used different severity
needed before establishing whether treatment with Lacto- scoring systems [9, 16]. The remaining study based the
bacillus plantarum is a beneficial alternative for wound clinical endpoint on patient symptomatology only [10]. Of
treatment. the seven studies that used SCORAD, only four studies
found a statistically significant decline in either the overall
3.4 Psoriasis SCORAD index or one parameter of assessment
[12, 14, 18, 20]. Furthermore, of the three studies that did
One study compared the effect of the probiotic Bifidobac- not conduct SCORAD analysis, two studies found a sta-
terium infantis 35624 on inflammatory markers in three tistically significant difference in QoL measurements [9] or
disease states: psoriasis, chronic fatigue syndrome, and skin severity grading [16], while the last study assessed
ulcerative colitis [24]. Twenty-six patients with psoriasis subjective symptoms only [10].
Table 2 Human clinical trials of probiotics, prebiotics, and synbiotics for the treatment of acne, wounds, and psoriasis in adults
Skin Study No. of subjects Study design Intervention Dosage Control or Primary Results Study limitation Jadad
condition and duration placebo outcome score
measures (RCT)

Acne Jung 45 12-week, Probiotic capsule: L. Per capsule: L. Minocycline Average total All three groups had SS decrease in Study only involved 1
vulgaris et al. Females with prospective, acidophilus (NAS super- acidophilus (NAS only acne lesion lesion count by week 4. NS difference fair-skinned
[22] mild to rand, open- strain), L. delbrueckii super-strain)— (100 mg/day) count between the three groups. By week females
moderate label study subsp bulgaricus (LB-51 5 billion CFU/capsule (Group B) Facial skin 12, Group C had a significantly lower Quality-of-life
acne, age super-strain), and B. L. delbrueckii subsp tolerability total lesion count than Groups A and questionnaire was
18–35 years bifidum (Malyoth super- bulgaricus (LB-51 (10-point B. There was no significant difference not validated
strain) (Group A) super-strain)— scale) between Groups A and B
Probiotic ? Minocycline 5 billion CFU/capsule QoL All three groups had a significant
(Group C) B. bifidum (Malyoth questionnaire reduction in inflamed lesion counts by
super-strain)— and AE Week 12. Group C had the most
20 billion CFU/capsule significant reduction compared with
Groups A and B. Group B had SS
more improvement than Group A
13% of patients in Group B developed
vaginal candidiasis
Wounds Peral 80 10-day, open- L. plantarum (strain NR) 105 culture of L. 3-mm layer of Microbial Proportional decrease in bacterial load Low number of 0
et al. Males and label study plantarum was applied silver burden at of 0.71 for the L. planatrum group, subjects per group
[23] females with to gauze at 1 ml/cm2— sulfadiazine 10 days using and 0.73 for the SD-Ag group (RR (between 12 and
burns aged gauze applied once (SD-Ag) 4-mm3 wound -2.72%) 15) did not permit
18–55 years daily for 10 days cream every tissue Relative rate values showed no power statistical
24 h for biopsies difference between groups in test
10 days
Probiotics, Prebiotics, and Synbiotics for Adult Dermatological Diseases

Clinical preventing infection, increasing

evaluation to granulation tissue, or healing in early
assess active third- or second-degree burns
granulation
tissue and
changes in
graft skin
color
Psoriasis Groeger 26 8-week, rand, Sachets of B. infantis 1 9 1010 CFU per sachet 5g Plasma CRP, Plasma CRP was SS reduced (-34%) in Subject number is 3
et al. Males and db, pc study 35624 per day maltodextrin IL-6, and the probiotic group after 8 weeks relatively low
[24] females aged per day TNFa compared with baseline. In comparing Only one daily dose
18–60 years pre- and post-feeding levels, CRP was of probiotic was
with SS reduced in probiotic-fed subjects administered,
moderate compared with placebo subjects therefore no dose-
chronic Plasma TNFa was SS reduced dependent anti-
plaque (-15.5%) in the probiotic group inflammatory
psoriasis compared with placebo (0%) at effect was
8 weeks, and pre- and post-feeding observed
levels of TNFa were also SS reduced No clinical
compared with placebo group. Plasma assessment of
IL-6 decreased in both groups after psoriasis was
8 weeks, but the results were NS conducted after
the probiotic
intervention

AE Adverse event, CFU colony forming unit, CRP C-reactive protein, db double-blind, IL interleukin, NR not reported, NS not statistically significant, pc placebo-controlled, QoL quality of life, Rand randomized, RCT randomized
controlled trial, RR relative rate, SS statistically significant, TNF tumor necrosis factor
 M. Notay et al.

Fig. 1 Study selection process

Manuscripts screened for review of
tle and abstract (n= 315)
Embase n= 197 Manuscripts included through manual
Cochrane Central Register of search of references (n=2)
Controlled Trials n= 105
MEDLINE n= 13

Manuscripts aer
duplicates removed (n= 314)

Manuscripts excluded (n= 293)

Manuscripts screened -study included infants, children, or

adolescents
(n= 314)
-study did not include probioc,
prebioc, or synbioc

Manuscripts for review of Manuscripts excluded aer review

full text (n= 21) of full text (n= 9)

-did not assess symptomac severity of a

dermatological condion
-probiocs was combined with other
supplements as only intervenon
-study was conducted on mice or among
healthy humans without dermatological
condions
-not available in English

Manuscripts selected from full

text review (n=12)

5 Discussion junctions to reduce gut permeability, helping with the

development of gut-associated lymphoid tissue (GALT),
On the basis of this systematic review, certain probiotic stimulating intestinal production of IgA, and downregu-
supplements and mixtures may be helpful in the treatment lating Th2 cytokines through the stimulation of IL-12 and
of AD in adults over the age of 18 years IFNc [25].
[9, 10, 12, 14, 16, 18, 20]. Many studies included small AD has been linked to the ‘hygiene hypothesis’. Early
sample sizes, which affected their generalizability. Overall, exposure to microbial agents can assist in the maturation of
there were a limited number of studies regarding the the Th1 cell response. In addition, this reduces the Th2 cell
treatment of AD, and even fewer regarding acne, psoriasis, response which contributes to the development of allergic
and wound care. The differences in study methodology, disease [14]. In pregnant women and newborns, probiotics
dose, type and duration of probiotic, and duration of fol- are thought to prevent and treat AD by promoting the
low-up may be responsible for the variations in outcomes. differentiation of naive T cells to mature Th1 cells [12]. In
Our systematic review demonstrated there is a limited adults, the mechanisms are not clear, although there appear
amount of research into the use of probiotics in adults with to be several possible modes of action. Beyond immune
dermatological diseases such as AD. Probiotics are thought modulation, different gut bacteria populations differentially
to benefit the immune system by reducing the adherence of correlate with the presence of long-chain saturated fatty
pathogenic bacteria, assisting with the maintenance of tight acids (LCFA) and short-chain fatty acids (SCFA) [26, 27].
Probiotics, Prebiotics, and Synbiotics for Adult Dermatological Diseases

LCFA and SCFA appear to interact with the immune Acknowledgements The authors thank Bruce Abbott for his assis-
system either by LCFA-based stimulation of TLRs [28] or tance in conducting the systematic search algorithms.
by modulation of regulatory T-cell function [29]. While Compliance with Ethical Standards
these hypotheses have been put forth with correlative
findings, more mechanistic studies are needed to prospec- Funding No funding was received for the preparation of this review.
tively assess how probiotics and prebiotics may interface
Conflict of interest Manisha Notay, Negar Foolad, and Alexandra R.
with the immune system and inflammation in ways that Vaughn have no conflicts of interests to declare. Raja K. Sivamani
would be relevant to the skin. serves as a scientific advisor for Dermveda.
Probiotics may be a useful adjunct to antibiotics in the
treatment of acne [22]. Researchers postulated the
improvement in the minocycline plus probiotic arm was References
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