A randomized double-blind placebo controlled trial to compare the safety and efficacy of probiotic formulation in Indian patients with Atopic Dermatitis

Atopic dermatitis (AD) is considered as a chronic inflammatory, pruritic and relapsing skin disease that is commonly associated with other atopic comorbidities (1). AD affects ~8% of the world populations with a reported prevalence ranges from ~10% of adults and ~20% of the paediatric population in developed countries (2-3). Complex pathophysiologi­cal mechanism of AD involves environmental, immune system and genetics factors. Role of microorganism has been suggested in the regulation of various biological processes in human body and human microbiome is considered as one of the human organ as they harbour organ specific niche in human body. Considering the diversity and organ-specific niches of the human microbiome, lesser is known about beneficial microbiota. However, with the introduction of high-throughput sequencing technology, understanding of Gut and skin microbiome has been significantly improved and their association with human disease pathogenesis is established including skin diseases like AD. The diagnostic of AD is based on clinical symptoms, whereas the SCORing for Atopic Dermatitis index (SCORAD) helps physicians to assess disease severity on a regular basis (4, 5). Mild to moderate cases are usually treated with emollients, topical steroids and phototherapy. In severe cases, oral corticosteroids and other systemic immunosup­pressants, including cyclosporine, methotrexate sodium or azathioprine sodium, may be required (6). The use of mon­oclonal antibodies and Janus kinase inhibitors has shown promising results in terms of both efficacy and safety (7). Several studies have demonstrated that immunological tolerance is closely related to the composition of intestinal microbiota (8). One of these functions is a contribution to the degradation of complex indigestible pol­ysaccharides and an essential role in the production of cer­tain nutrients. Furthermore, short-chain fatty acids (SCFAs) resulting from fermentation of dietary fibre by bacteria in the gastrointestinal tract play a protective role against bacterial translocation from the intestinal lumen. Those patients whose intestinal microbiota is rich in SCFA-producing bacteria have a lower tendency to suffer bacterial translocation from the gut (9) and a negative correlation was observed with disease severity. Indeed, this phenomenon may be partly responsible for the interconnection between the intes­tinal and skin microbiota and may modulate the immune and metabolic response of the skin, which would affect the microbial composition of the skin itself (10). Substantial evidences indicated the association between microbial dysbiosis and development of allergic disease conditions (11) and there are various factors reported to influence the gut and skin microbial homeostasis for e.g. mode of delivery (C-section vs normal vaginal delivery), the type of feeding, antibiotic use, diet (breast milk vs children fed with formula or in a mixed manner (12). Probiotics are described as “live microorganisms which when administered in adequate amounts confer health benefits to the host,” the definition is given with the agreement of the World Health Organization (WHO) and the Food and Agriculture Organization (United Nations) (13). Despite extensive research, only a few bacterial strains have proven their potential in terms of safety and efficacy e.g. Bifidobacterium and Lactobacillus species. There are various clinical trials performed to prove the safety and efficacy of probiotics in Atopic dermatitis but contradictory findings reported that warrant the further investigations (14-19). The contradictory findings may be attributed to various factors such as different populations, different probiotic formulation, targeting different age groups, duration of probiotic consumption and follow up durations. Considering the above mentioned facts further randomized clinical trial based investigation is highly warranted to assess the efficacy of the probiotics in AD. Therefore, the aim of the present study is to perform a randomized double-blind placebo controlled trial to compare efficacy of probiotic formulation (developed by Unique Biotech, FSSAI approved nutraceuticals) in Indian patients with Atopic Dermatitis in paediatric population with age group of two to 18 years by assessing the SCORAD index and status of inflammatory cytokines. The probiotic formulation (i.e. Onegram sachet containingfive Billion colony forming units (CFU) ofLactobacillus johnsonii UBLJ (01-3.8 billion CFU), Bifidobacterium breve UBBr (01-0.6 billion CFU), Lactobacillus fermentum UBLF (31-0.3 billion CFU), Lactobacillus reuteri UBLRu (87-0.3 billion CFU) along with Vitamin D3 (cholecalciferol, 400 IU), Vitamin E (d-alpha tocopherol, 4mg/6 IU, Fructooligosaccharide (100 mg).

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