ORIGINAL RESEARCH

published: 06 September 2017

doi: 10.3389/fcimb.2017.00392

Probiotics for the Treatment of Atopic

Dermatitis in Children: A Systematic
Review and Meta-Analysis of
Randomized Controlled Trials
Ruixue Huang 1 , Huacheng Ning 1 , Minxue Shen 2, 3 , Jie Li 2, 3 , Jianglin Zhang 2, 3 and
Xiang Chen 2, 3*
1
Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University,
Changsha, China, 2 Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China, 3 Hunan Key
Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, China

Objective: Atopic dermatitis (AD) is a prevalent, burdensome, and psychologically

important pediatric concern. Probiotics have been suggested as a treatment for AD.
Some reports have explored this topic; however, the utility of probiotics for AD remains
to be firmly established.
Methods: To assess the effects of probiotics on AD in children, the PubMed/Medline,
Cochrane Library Scopus, and OVID databases were searched for reports published in
the English language.
Results: Thirteen studies were identified. Significantly higher SCORAD values favoring
probiotics over controls were observed (mean difference [MD], 3.07; 95% confidence
Edited by: interval [CI], 6.12 to 0.03; P < 0.001). The reported efficacy of probiotics in children
Pascale Alard, < 1 year old was 1.03 (95%CI, 7.05 to 4.99) and that in children 118 years old was
University of Louisville, United States
4.50 (95%CI, 7.45 to 1.54; P < 0.001). Subgroup analyses showed that in Europe,
Reviewed by:
Valerio Iebba, SCORAD revealed no effect of probiotics, whereas significantly lower SCORAD values
Sapienza Universit di Roma, Italy were reported in Asia (MD, 5.39; 95%CI, 8.91 to 1.87). Lactobacillus rhamnosus
Arianna Aceti,
GG (MD, 3.29; 95%CI, 0.30 to 6.88; P = 0.07) and Lactobacillus plantarum (MD,
Universit di Bologna, Italy
0.70; 95%CI, 2.30 to 0.90; P = 0.39) showed no significant effect on SCORAD values
*Correspondence:
Xiang Chen in children with AD. However, Lactobacillus fermentum (MD, 11.42; 95%CI, 13.81 to
chenxiang_xy@126.com 9.04), Lactobacillus salivarius (MD, 7.21; 95%CI, 9.63 to 4.78), and a mixture
of different strains (MD, 3.52; 95%CI, 5.61 to 1.44) showed significant effects on
Received: 19 May 2017
Accepted: 22 August 2017 SCORAD values in children with AD.
Published: 06 September 2017
Conclusions: Our meta-analysis indicated that the research to date has not robustly
Citation:
Huang R, Ning H, Shen M, Li J,
shown that probiotics are beneficial for children with AD. However, caution is needed
Zhang J and Chen X (2017) Probiotics when generalizing our results, as the populations evaluated were heterogeneous.
for the Treatment of Atopic Dermatitis
Randomized controlled trials with larger samples and greater power are necessary to
in Children: A Systematic Review and
Meta-Analysis of Randomized identify the species, dose, and treatment duration of probiotics that are most efficacious
Controlled Trials. for treating AD in children.
Front. Cell. Infect. Microbiol. 7:392.
doi: 10.3389/fcimb.2017.00392 Keywords: probiotics, constipation, children, meta-analysis, randomized controlled trial

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Huang et al. Probiotics for the Treatment of Atopic Dermatitis

INTRODUCTION Exclusion Criteria

Studies that did not meet the inclusion criteria or that were
Atopic dermatitis (AD), is one of the most common chronic published in languages other than English were excluded.
inflammatory skin disorders among infants and children. AD is
characterized by itching and recurrent eczematous lesions, and its Search Process
incidence has increased worldwide over the past several decades. Two individuals of our team searched the following databases
The current prevalence rate is 1020% in infants and children from the times of the earliest records in 2000 to April 12, 2017:
(Weidinger and Novak, 2016). As the leading non-fatal medical PubMed (https://www.ncbi.nlm.nih.gov/pubmed), Embase
skin disorder, AD imposes severe psychosocial burdens on (https://www.embase.com/login), Cochrane Library (http://
pediatric patients and their families (Chamlin and Chren, 2010; www.cochranelibrary.com/) and Scopus (https://www.elsevier.
Silverberg, 2016; Sidbury and Khorsand, 2017). AD is associated com/solutions/scopus) (available on the internet); and Ovid,
with high risks of allergy, asthma, and mental health issues Orbis, and the Web of Science (available at our university library
(Sung et al., 2017). Infants and children with AD are typically with free downloads). The following search string was used
treated with topical corticosteroids (TCS), antihistamines, and in searching: [(infant OR infants) OR (neonate OR neonates)
even antibiotics (Totri et al., 2017). However, these medications OR (newborn OR newborns) OR (toddler OR toddlers)] AND
exert several adverse side effects, and AD symptoms may recur (probiotic OR probiotics OR pro-biotics OR probio ) AND
rapidly after treatment is stopped. Furthermore, long-term TCS (atopic dermatitis OR atopic eczema) OR (SCORAD) OR (atopic
use may trigger new-onset AD. OR atopy) NOT (animals) NOT (adult). The references listed
Probiotics is becoming increasingly attractive as a treatment in each report were examined to allow us to retrieve additional
option for some illnesses in children (Fuchs-Tarlovsky et al., information. We only reviewed works in the English language,
2016). Probiotics (live bacteria or yeasts) are not necessarily thus not those in (for example) Korean or Chinese. Furthermore,
harmless, but they help to protect hosts from harmful conference abstracts were excluded, because they lacked detailed
bacteria (Mizock, 2015). When administered in adequate data.
amounts, probiotics may play beneficial roles not only in
the gastrointestinal tract but also in the gutbrainskin axis Data Collection
(Ogden and Bielory, 2005; Dehingia et al., 2015; Huang et al., The two individuals collected all data independently. The
2016; Huang and Hu, 2017). Several studies on the benefits eligibility of studies was confirmed by both reviewers. A
of probiotics for pediatric AD patients have appeared over the tabulation of study author(s), publication date, recruited
past decades. In 2000, Pessi et al. reported that oral probiotics numbers, probiotic strain(s), dosage, treatment duration, and
alleviated the clinical symptoms of gastrointestinal inflammation treatment results was prepared (Table 1). If the study data were
and AD (Pessi et al., 2000). Kirjavainen et al. (2003) reported unclear, we attempted to contact the corresponding author via
lower Bacteroides counts in the fecal microflora of children email to obtain further information.
with atopic eczema than in healthy infants and suggested that
probiotics can be used to treat AD in children (Kirjavainen Statistical Analysis
et al., 2003); however, some reports yielded contrasting results RevMan 5.3 software (Cochrane Collaboration, Nordic Cochrane
(Licari et al., 2015). For instance, Gruber et al. found that Center, Copenhagen, Denmark; http://community.cochrane.
Lactobacillus rhamnosus strain GG (LGG) exerted no therapeutic org/tools/review-production-tools/revman-5/) was accessed to
effects in infants with mild-to-moderate AD (Gruber et al., 2007). conduct the meta-analysis. SCORAD was commonly used to
Therefore, we systematically evaluated the effects of probiotics measure the efficacy of probiotics in children with AD. As
used to treat AD in children. the results were continuous data, the mean difference (MD)
and 95%CI were calculated for statistical analyses, and either
METHODS a randomized-effects model or fixed-effects model was used
depending on whether heterogeneity was apparent. Subgroup
Inclusion Criteria assessment was performed with regard to different geographical
The inclusion criteria for the meta-analysis were (1) RCTs of status, infants aged <1 year, children aged between 1 and
children aged 18 years in whom AD severity was graded by 18 years, different strains, and LGG. The c2 test was used to
experienced dermatologists using the Severity scoring of atopic identify statistical heterogeneity (Margolis and Mitra, 2017). The
dermatitis: the SCORAD index (1993); Yoon et al. (2015) (2) that I2 statistic was calculated to identify and quantify inconsistency.
evaluated the use of any probiotic culture/strain/dose/therapy When I2 was 50%, indicating significant heterogeneity, we used
regimen (including studies on fermented yogurt; all dosage a random-effects model for meta-analysis. When I2 was < 50%
forms including tablets, powders, oil suspensions, and capsules indicating no heterogeneity, we employed a fixed-effects model.
were included). All results are presented as means standard Publication bias was assessed by constructing funnel plots. A
deviation. However, if multiple reports evaluated the same group two-tailed P < 0.05 was used to reflect statistical significance.
of patients, we selected only the most recent complete report. Sensitivity analyses, also termed uncertainty analyses, were used
SCORAD, developed by the European Task Force on AD in 1993 to explore the extent to which our results and conclusions were
(1993), assesses the AD area, clinical features, visual analog scale altered by changes in the data or analysis approach (Alexander
data, and clinical symptoms, and it is widely used to evaluate AD et al., 2016). If the conclusions did not change upon application of
severity in children (Machura et al., 2008). the sensitivity analysis, those conclusions were considered robust.

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Huang et al. Probiotics for the Treatment of Atopic Dermatitis

TABLE 1 | Characteristics of included RCTs for meta-analysis.

Study, year (country) n Age Genus, species, and strain, Dose Outcome summary
duration

Viljanen et al., 2005; 220 1.411.9 months Lactobacillus rhamnosus strain GG 5 109 cfu or mixture twice Positive effect of probiotics was seen
Finland (LGG); 4 weeks daily capsules only in IgE-sensitized infants
Weston et al., 2005; 56 618 months LF; 8-week 2 1010 CFU/g /d Positive effect of probiotics was seen
Austria only in food-sensitized children
Folster-Holst et al., 2006; 54 155 months Lactobacillus rhamnosus strain 10 109 CFU No significant difference between
Germany GG(LGG); 8-week synbiotics and placebo
Gruber et al., 2007; 102 312 months Lactobacillus rhamnosus strain >5 109 CFU, twice daily No significant difference between
Germany GG(LGG); 8-week orally synbiotics and placebo
Niers et al., 2009; 98 124 months B. bifidobacterium infantis, LC. 3 109 CFU, once daily No difference was observed among
Netherland lactis W58; 24-week two groups
Wu et al., 2012; Taiwan 60 214 years Lactobacillus (LS), 8-week 5 1010 CFU, twice daily SCORAD decrease significantly in
probiotic group compared to placebo
group
Gerasimov et al., 2010; 90 13 years Mixture (LA t BL)/synbiotics; 8-week 5 1010 CFU, twice daily SCORAD decrease significantly in
Ukraine probiotic group compared to placebo
group
Woo et al., 2010; Korea 75 210 years Lactobacillus (LS2)/synbiotics; 2 1010 CFU, twice daily SCORAD decrease significantly in
12-week probiotic group compared to placebo
group
Shafiei et al., 2011; Iran 41 136 months Seven strain probiotics plus 1 109 CFU, once daily No significant difference between
prebiotic mixture; 2 months probiotics and placebo
Gore et al., 2012; UK 133 36 months Lactobacillus (LP) or 1 1010 CFU No significant difference between
Bifidobacterium (BL); 12-week probiotics and placebo
Han et al., 2012; Korea 83 113 years Lactobacillus (LP2); 12-week 5 1010 CFU, twice daily SCORAD decrease significantly in
probiotic group compared to placebo
Yesilova et al., 2012; Turkey 39 112 years Mixture (BB2, LA, LC, LS2); 8-week 4 1010 CFU, daily SCORAD decrease significantly in
probiotic group compared to placebo
Wang and Wang, 2015; 220 128 years Lactobacillus paracasei(LP), LP,LF(2 1010 CFU,qd); SCORAD decrease significantly in
Taiwan Lactobacillus fermentum(LF), Mixture(4 1010 CFU,qd) probiotic group compared to placebo
Mixture; 3 months

In meta-analyses, sensitivity analyses are conducted by excluding

studies one-by-one to identify those studies that materially affect
the results (Copas and Shi, 2000). The risk of bias in each RCT
was explored using the risk of risk tool in Revman software.
The PRISMA statement published in 2009 aimed to improve
the reporting of systematic reviews and meta-analyses. PRISMA
defines an evidence-based minimum set of items to employ, and
we followed this guideline (http://www.prisma-statement.org/).
PRISMA features both a checklist and a flow diagram. We used
the checklist to ensure that our study structure was appropriate
and the flow diagram to map the numbers of records identified,
included, and excluded, as well as the reasons for exclusion
(Zhang et al., 2017). Publication bias was checked by drawing
funnel plots, which are commonly used in systematic reviews and
meta-analyses. Publication bias is considered absent if the study
results are distributed in close proximity to the averages.

RESULTS
Included Studies
The PRISMA flow diagram (Figure 1) shows how we selected
the relevant reports. We initially screened 392 articles, excluded
those that did not meet our inclusion criteria, and finally retained FIGURE 1 | PRISMA flow diagram of articles included in the meta-analysis.
26 articles. As some reports did not report data as means SD,

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Huang et al. Probiotics for the Treatment of Atopic Dermatitis

we contacted the corresponding authors by email. Unfortunately, RCTs that adhered to high standards. Four studies divided
we sent 13 emails and didnt receive any data suitable for children into probiotic intervention and control groups; two
inclusion in the meta-analysis. Ultimately, 13 studies involving studies created three groups (probiotics, a placebo, and another
1,070 children fulfilled our selection criteria (Table 1). intervention). Twelve studies were of double-blind design. All
13 studies reported baseline data including socioeconomic status
Quality Assessment and mean age; these did not differ significantly among the groups.
Figure 2A shows the risk of bias within all enrolled RCTs, as
adjudged by the two reviewers. Figure 2B presents the individual Probiotics and Children with AD
risks of bias, again as perceived by the reviewers. Both figures Data from 1,070 children (intervention group, 553; control
show that the risks of bias were rather low, because all were group, 517) were assessed. The outcome of a random-effects

FIGURE 2 | (A) Risk of bias graph, with each risk of bias item presented as a percentage across all included studies. (B) Risk of bias summary, with each risk of bias
item for each included study.

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Huang et al. Probiotics for the Treatment of Atopic Dermatitis

meta-analysis model involving all 13 trials is shown in Figure 3. (95%CI, 13.76 to 8.64). However, there was heterogeneity
Significant differences in SCORAD values favoring probiotics among these trials (Figure 5).
over the control were observed overall (MD, 3.07; 95%CI,
6.12 to 0.03; P < 0.00001). However, a high degree of Subgroup Assessment of Different
heterogeneity was observed across these 14 trials (I2 = 87%).
Cultured Organisms
Subgroup Analysis of Probiotics Efficacy MD scoring compared to control and placebo interventions was
performed by cultured organism group. LGG (MD, 3.29; 95%CI,
by Age 0.30 to 6.88; P = 0.07) and LP (MD, 0.70; 95%CI, 2.30
All 13 trials involved children aged 018 years. We categorized
to 0.90; P = 0.39) showed no significant effects on SCORAD
the children into two groups: infants <1 year old and children
values in children. However, LF (MD, 11.42; 95%CI, 13.81 to
118 years old. Accordingly, five trials were included in the <1
9.04), LS (MD, 7.21; 95%CI, 9.63 to 4.78), and a mixture
year subgroup, and nine trials were included in the 118 years
of different strains (MD, 3.52; 95%CI, 5.61 to 1.44) showed
subgroup (Figure 4). The efficacy of probiotics in the former
significant effects on SCORAD values in children (Figure 6).
subgroup was 1.03 (95%CI, 7.05 to 4.99) and that in the
latter subgroup was 4.50 (95%CI, 7.45 to 1.54; P < 0.001).
However, a high degree of heterogeneity was observed among the Publication Bias
<1 year subgroup (I2 = 94%). We used RevMan software to draw funnel plots (Figure 7),
wherein each dot represents data from a single RCT. A random-
Subgroup Assessment by Continent effects model was used to this end. The funnel plots were
Subgroup assessment by continent showed different effects. In somewhat asymmetrical, thus indicating potential publication
Europe, probiotics showed no effect on SCORAD, whereas bias, perhaps attributable in part to the fact that we included
significantly lower SCORAD values were reported in Asia (MD, only English-language publications and excluded conference
5.39; 95%CI, 8.91 to 1.87). In Australia, the MD was 11.20 abstracts. However, studies with positive outcomes are more

FIGURE 3 | MD scoring with probiotics treatment compared to control and placebo interventions. 95%CI, 95% confidence interval.

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Huang et al. Probiotics for the Treatment of Atopic Dermatitis

FIGURE 4 | MD scoring with probiotics treatment compared to control and placebo interventions by age group.

likely to be published than are those with negative outcomes, thus Lactobacillus plantarum (LP)showed no effect in children
creating bias. with AD.
Hippocrates (460370) stated that All diseases begin in
Sensitivity Testing the gut, which is the earliest suggestion that bacteria affect
We performed sensitivity analyses to assess the relative influence health (Hippocrates, 2002). Metchnikoff, known as the father
of each study by excluding the studies one by one, and the of probiotics (Gordon, 2016), proposed that colonic bacteria
results suggested no significant changes in effects with regard to afforded health benefits in aging adults. In recent decades,
subgroups. probiotics that aid in the resolution of pediatric atopic eczema
have been investigated. Viljanen et al. explored probiotic effects
DISCUSSION on pediatric atopic eczema/dermatitis syndrome but found no
significant difference between the treatment and control groups
Overall, the data suggested an overall benefit of probiotics (Viljanen et al., 2005). Passeron et al. compared probiotics
supplementation in children with AD, and age-specific sub- and prebiotics and found that both significantly improved AD
analyses showed that probiotics effectively reduce SCORAD manifestations in children (Passeron et al., 2006). Brouwer et al.
values in children aged 118 years. Geography-specific sub- evaluated the clinical and immunological effects of Lactobacillus
analyses showed that probiotics effectively reduced SCORAD rhamnosus (LR) supplementation in a hydrolyzed formula given
values in Asia, while no effect was observed for Europe. to children with AD but found no significant effect (Brouwer
Strain-specific sub-analyses indicated that Lactobacillus (LS), et al., 2006). The cited authors suggested that the discrepancies
Lactobacillus fermentum (LF), and a probiotic mixture reduced between their results and those of other trials were likely
SCORAD values in children with AD, while LGG and attributable to differences in treatment timing and the strains

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Huang et al. Probiotics for the Treatment of Atopic Dermatitis

FIGURE 5 | MD scoring with probiotics treatment compared to control and placebo interventions by location.

used. Sistek et al. conducted a 12-week trial in the UK and found be attributable to restoration of the altered intestinal microbiota
that a combination of LR and Bifidobacteria lactis (BL) improved (Drago et al., 2011). In contrast, Gore et al. found that LS exerted
AD symptoms in food-sensitive children (Sistek et al., 2006). At no beneficial effects on eczema when given as an adjunct to
roughly the same time, a prospective German study by Folster- basic topical treatment (Gore et al., 2012). Several reports have
Holst et al. yielded insufficient evidence to make the conclusion examined the effects of other bacterial strains on AD in children.
that LGG is an effective treatment for moderate-to-severe AD in Supplementation with LPCJLP 133, Lactobacillus paracasei, and
infants (Folster-Holst, 2010). Gruber et al. also found that LGG LF was reported to be effective. The discrepancies described
had no therapeutic effect in such patients (Gruber et al., 2007). above may be attributable to differences in the strains used, the
Despite these discouraging findings, Gerasimov et al. reported study areas, and/or the ethnicities of the subjects. Several groups
that Lactobacillus acidophilus DDS-1 and Bifidobacterium lactis have performed meta-analyses to evaluate the effectiveness of
UABLA-12 afforded significant clinical improvements in children probiotics on AD. Da Costa Baptista et al. reviewed all published
with moderate-to-severe AD (Gerasimov et al., 2010). Similarly, trials and reported that the biological effects observed in most
Wu et al. showed that Lactobacillus salivarius (LS) exerted short- trials suggest that probiotic adjuvant treatments are of benefit for
term beneficial effects in patients with moderate-to-severe AD AD (da et al., 2013). The cited review, although comprehensive,
(Wu et al., 2012). Drago et al. suggested that such effects may did not report total MDs or 95%CIs. Chang performed a

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Huang et al. Probiotics for the Treatment of Atopic Dermatitis

FIGURE 6 | MD scoring with probiotics treatment compared to control and placebo interventions by cultured organisms.

meta-analysis of studies in which either prebiotics or probiotics the effects of probiotics in the treatment of AD in patients of
were given and reported that synbiotics may be useful to treat AD all ages. They observed significant differences in SCORAD values
(Chang et al., 2017). However, the focus was on synbiotics rather favoring probiotics over the control group in children 118 years
than probiotics. Szajewska et al. stressed the need for data on old and in adults, whereas no favorable effects were seen in
individual probiotic strains rather than on probiotics in general infants <1 year old (Kim et al., 2014). We found that probiotics
(Szajewska and Mrukowicz, 2003; Szajewska et al., 2015). Ogden were efficacious in children aged 118 years (MD, 4.50; 95%CI,
et al. suggested probiotics as a complementary approach to the 7.45 to 1.54) and showed strong efficacy in Asia but not in
treatment and prevention of pediatric AD (Ogden and Bielory, Europe; furthermore, LGG had no effects on AD whereas LS,
2005). They concluded that probiotics should be an active area LF, LP, and a mixture of strains showed beneficial effects. Our
of investigation, considering the role of gut microbiota in altered findings are in agreement with those of Lee et al., who concluded
immune responses in atopic patients. However, the authors did that the evidence for probiotics as a useful treatment of AD
not perform a meta-analysis to obtain further details about the in children is convincing. However, the cited authors reviewed
treatment effects of probiotics. Kim et al. reviewed 25 RCTs on only trials published before 2008, whereas we included later

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Huang et al. Probiotics for the Treatment of Atopic Dermatitis

effects of LP on AD (MD, 0.70; 95%CI, 2.30 to 0.90; P = 0.39).

This discrepancy may be associated with differences in dosages,
the timing and duration of intervention, and sample sizes, and
further trials are required to clarify this point.
Our meta-analysis had certain limitations. First, we attempted
to minimize heterogeneity and publication bias, but significant
heterogeneity among trials remained evident. Differences in
study samples, study populations, and intervention methods
contributed to the heterogeneity. For example, some of the
included studies had small sample sizes, compromising the
reliability and validity of the conclusions. In addition, the
RCTs were performed in various countries, thus, the subjects
differed among RCTs in terms of their genetic make-up and
microbial exposure, which in turn are associated with varying
responses to the same probiotic. Also, we excluded some
FIGURE 7 | Funnel plot: SD by mean difference and each dot represents 1 RCTs from this meta-analysis, and fewer studies included will
RCT. reduce the confidence associated with the data interpretation
and increase heterogeneity and publication bias. Finally,
we cannot draw robust conclusions as to which probiotic
trials to afford greater insight. The differences may be because strain/mixture should be given to children with AD and
we included only RCTs involving children under the age of which population(s) would receive maximum benefit from such
18 years and those that reported MDs. Some RCTs presented treatment.
values other than MDs, including the study by Kim et al. (2010),
and some presented the results as figures, rendering calculations CONCLUSION
impossible. We contacted the corresponding authors but did not
receive useful replies. Thus, we excluded those studies. Third, Our present work demonstrated that probiotics may have the
some of the included studies had small sample sizes, which may potential to decrease SCORAD values in children with AD.
affect the reliability and validity of the conclusions. Thus, our However, the findings presented here must be generalized
overall results are affected by these issues, and the data were with caution because of heterogeneity. The results are a
highly heterogeneous. These topics require further attention. source of optimism with regard to the management of AD in
Also, in the subgroup analyses, children with AD may have children. More adequately powered RCTs using standardized
different gut microbiota profiles from those of normal children. measurements are necessary to assess which species of probiotics
Thus, probiotics supplementation in children < 1 year old and and dosages and what treatment periods are most efficacious for
118 years old may promote a healthier gut microbiota profile, children with AD.
boosting their immune response. People from different areas
have different dietary structures and gut bacterial compositions. AUTHOR CONTRIBUTIONS
Dehingia et al. compared gut bacterial diversity between Indian
populations and worldwide data (Dehingia et al., 2015). Zhang RH, MS, and XC proposed the idea of this study and designed
et al. also suggested that a phylogenetically diverse gut microbiota the study; RH, HN, MS, and JL conducted data screening
at the genus level may be commonly shared by distinctive healthy and performed quality assessment; RH and MS used RevMan
populations, which may explain the diversity of the effects of software to assess the data and performed the statistical analysis
probiotics across people from different countries (Zhang et al., and gave the explanations of the statistical results. RH drafted the
2015). The above discussion is of importance to physicians, initial manuscript. JL, JZ, and XC critically reviewed and revised
dermatologists, and other public healthcare workers who deal the manuscript.
with diverse ethnic populations.
To the best of our knowledge, there are no previous reports FUNDING
on the effects of different probiotic strains on AD in children. In
our meta-analysis, all trials involving LGG and one trial involving This work was supported by Chinas National Basic Work of
LP showed no effects, while two studies confirmed the beneficial Science and Technology (Grant# 2015FY111100).

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randomized, clinical trial of efficacy and safety. Br. J. Dermatol. 166, 129136. Conflict of Interest Statement: The authors declare that the research was
doi: 10.1111/j.1365-2133.2011.10596.x conducted in the absence of any commercial or financial relationships that could
Yesilova, Y., Calka, O., Akdeniz, N., and Berktas, M. (2012). Effect of probiotics on be construed as a potential conflict of interest.
the treatment of children with atopic dermatitis. Ann. Dermatol. 24, 189193.
doi: 10.5021/ad.2012.24.2.189 Copyright 2017 Huang, Ning, Shen, Li, Zhang and Chen. This is an open-access
Yoon, J. H., Nam, Y., Song, E. Y., Roh, E. Y., Yoon, H. S., and Shin, S. (2015). CCL28 article distributed under the terms of the Creative Commons Attribution License (CC
cannot replace ige for severity by objective SCORAD index in atopic dermatitis BY). The use, distribution or reproduction in other forums is permitted, provided the
in children. Clin. Lab. 61, 15771580. doi: 10.7754/Clin.Lab.2015.150311 original author(s) or licensor are credited and that the original publication in this
Zhang, J., Guo, Z., Xue, Z., Sun, Z., Zhang, M., Wang, L., et al. (2015). journal is cited, in accordance with accepted academic practice. No use, distribution
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