Efficacy of probiotic supplementation in the treatment of psoriasis—A systematic review and meta‐analysis

Many studies have emphasized the possible role of probiotics in psoriasis, probiotic supplementation might be helpful to treat psoriasis. This study systematically evaluated the efficacy of probiotic supplementation for the treatment of psoriasis.

0][11] These classic treatments are focused on reducing skin inflammation and immunomodulation.Developmental biology studies have shown that both skin cells and intestinal cells originate from the same embryonic layer and have similar signaling mechanisms.At the same time, the skin and gut are also key immune and neuroendocrine organs, and there is a close link between gut health and skin homeostasis.The "gut-skin axis" theory is a well-established theory that has been closely linked to gut health and skin homeostasis. 12Studies have shown that gut microbiome can maintain skin immune homeostasis by mediating both innate and adaptive immunity. 12Some studies found that oral probiotics may reverse thepro-inflammatory and anti-inflammatory immune imbalance by modulating the gut flora, thereby reducing skin inflammation of mice. 13A study showed that probiotics can modulate immune responses by regulating the intestinal flora, thereby effectively ameliorating skin inflammation in psoriasis.Effectively improve skin inflammation in psoriasis. 14The mechanism may be to increase the enrichment of Foxp3+ regulatory T cells to the skin and reduce apoptosis-mediated skin inflammation, thus restoring homeostasis through immunomodulation. 14us, probiotics may have a therapeutic effect on psoriasis through immunomodulation of gut microbiome.

| MATERIAL S AND ME THODS
This meta-analysis was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement, and we have registered in the PROSPERO (CRD42023483637).

| Search strategy
We searched some databases until November 10, 2023, including Cochrane Library, Embase, Web of Science, and PubMed.Some keywords were combined to retrieve the relevant studies including medical subject heading (MeSH), title, and abstract.The following search strategy was as follows (ProbioticAND Psoriasis OR Psoriases Pustulosis of Palms).

| Inclusion criteria
Inclusion criteria included randomized controlled trials (RCTs) published in English, diagnosed with psoriasis and the test groups were treated with probiotic and the control groups were treated with placebo.The primary outcomes are Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI), which are the main criteria for evaluating the severity of psoriasis.The higher scores indicate more severe disease, and conversely, the lower the scores revealed the milder the disease.

| Exclusion criteria
Exclusion criteria including non-RCTs pregnant or lactational women and not relevant to the content of the experimental and control groups duplicated publications and animal trials and studies with unavailable data (Figure 1).

| Literature screening and data extraction
Two independent authors (LY Lai and X He) screen title and abstracts of studies from the eligibility criteria and then exclude irrelevant studies.The full text of the retained studies was then read to identify studies for inclusion.Disagreements and discrepancies were resolved by the third author.The authors (LY Lai and X He) extracted the data from included trial.All data regarding study characteristics, interventions, comparisons, and outcomes were extracted.We contacted the investigators of the studies by e-mail when necessary to obtain raw or missing data (Table 1).We also counted the probiotics included in these studies (Table 2).

| Assessment of methodological quality
We chose the Cochrane collaboration's tool 15 to evaluate the methodological quality of each included trial.The included studies were marked as low, high, or unclear risk of bias in seven items.
The disagreement was resolved by discussing with the other author (Figure 2A,B).

| Statistical analysis
We chose Review Manager (RevMan) 5.3 for data analysis.Review Manager version 5.3 was used for meta-analyses.For continuous data with the same measurement unit, we used the weighted average difference and 95% confidence interval for continuous data with same measurement unit measurement units, On the contrary, we use the standardized average balance and 95% confidence interval.If I 2 > 50% or p < 0.05, indicating a significant heterogeneity, a random-effect model was used.Otherwise, a fixed-effect model was applied for statistical analysis. 16,17When 10 or more studies were included in the same outcome, the potential publication bias was assessed by using funnel plot.A two-tailed p < 0.05 was considered to be statistically significant.

| RE SULTS
We retrieved 454 studies from four literature databases.After removing duplicated literatures, 78 studies remained for further selection.Thirty-eight studies were removed by screening their abstract and title.Thirty-five studies were excluded by reading full text.
Ultimately, five studies were included in this study.The flowchart of the study selection process is shown in Figure 1.
Figure 2A shows the risk of bias of randomized controlled trials, because of all studies did not report adverse events and elective reporting were marked as unclear risk, in terms of other bias, all studies did were rated as low risk.Table 1 show the characteristics of the included studies.

| Publication bias
All outcomes were constrained by the number of studies (n < 10), so we did not adopt publication bias detection.

| DISCUSS ION
In this study, we reviewed and comprehensively summarized randomized controlled, indicating some important information.This meta-analysis revealed that PASI and DLQI score were decreased after probiotic supplementation as a treatment for psoriasis.
Psoriasis is a common immune-mediated chronic inflammatory skin disease that can be triggered by genetic and immunologic, infected, and metabolic disorders. 23e association between probiotic deficiency and psoriasis uncertain, but some studies have suggested possible roles of probiotic in psoriasis.Some studies demonstrated that gut microbiota is associated with inflammatory dermatosis.
Microbiome dysbiosis may lead increased epithelial permeability of the intestinal mucosa and activation of effector T cells disturb the balance between them and regulatory T cells, while proinflammatory cytokines further enhance epithelial permeability and create chronic systemic inflammation. 24Some studies reported that two beneficial bacterial species (Parabacteroides and Coprobacillu) is obviously decreased in the patients of psoriatic arthritis. 25An animal experiment indicated Oral supplementation of psoriasis-like mice with probiotics significantly modified their psoriasis-like pathological phenotype and inhibited the release of inflammatory cytokines associated with the IL-23 /Th17 cell axis. 26ese research results showed gut microbiota play an important

F I G U R E 3 Psoriasis Area and Severity Index (PASI).
F I G U R E 4 Dermatology Life Quality Index (DLQI).
role in psoriasis.8][29] The mechanism of action of probiotic supplementation in patients with psoriasis may be related to increased levels of acetate And propionate in the gut, which have been linked to the suppression of cytokine activity. 30e study included five randomized double-blind clinical trials and concluded that probiotic supplementation decreased the PASI and DLQI score and probiotic supplementation benefits psoriasis patients.Meanwhile, more and more researches showed that psoriasis is always associated with metabolic syndrome.Psoriasis also is considered as an independent risk factor for cardiovascular disease. 31Some researches found probiotic supplements, such as inulin and fructooligosaccharides could decrease cholesterol and triglyceride levels in both in vivo and in vitro studies. 32A study also reported probiotic supplements decreased uric acid. 32In conclusion, probiotic supplementation could not only alleviate the symptom of psoriasis but also decrease cholesterol and triglyceride levels and uric acid.Several studies have shown a relationship between gut flora and skin. 33Moreover, dysregulation of microbiota has been seen in some inflammatory skin conditions, such as psoriasis, acne, seborrheic dermatitis, and atopic dermatitis. 34[37][38][39] The experimental group in this study contained a variety of probiotics, including single-strain probiotics and multi-strain mixtures probiotics.
These probiotics have shown good efficacy in the treatment of psoriasis and some research showed that in most cases, multi-strain mixtures were not significantly more effective than single-strain probiotics. 40Although, biologics have become the mainstay of treatment for psoriasis, but the disease requires long-term maintenance therapy, and probiotics have some efficacy as a complementary treatment and appear to be better at stabilizing the disease in maintenance therapy.Of course, more clinical studies are needed to confirm these conclusions.
However, we also have some limitations in this study.
First, the number of included studies and sample were relatively small, the results need to prove by lots of multi-center, large-sample clinical studies.Second, the efficacy of the meta is only based on clinical scores, we need more laboratory indicators to demonstrate it.

| CON CLUS ION
We systematically and comprehensively reviewed the relevant studies, these studies revealed probiotic is helpful in the treatment of psoriasis and the results of this meta summarized the evidence for the role of probiotic in psoriasis patients in comparison with a placebo group, probiotic supplementation decreased psoriasis severity

F I G U R E 1
Selection of the included studies.TA B L E 1 Characteristics of the included studies.
and improved the symptoms and clinical signs of psoriasis.However, the specific mechanisms underlying are still unclear.More highquality, large-sample, and long-term trials are required to figure out the underlying mechanisms and provide more reliable and accurate efficacy evidence in the future.

Table 2
show the types of probiotics of the included studies, which contain Lactobacillus rhamnosus, Bifidobacterium, Lactobacillus acidophilus, and Streptococcus thermophilus.