Probiotic Strains and Intervention Total Doses for Modulating Obesity-Related Microbiota Dysbiosis: A Systematic Review and Meta-analysis.

Obesity is a growing health threat worldwide. Administration of probiotics in obesity has also parallelly increased but without any protocolization. We conducted a systematic review exploring the administration pattern of probiotic strains and effective doses for obesity-related disorders according to their capacity of positively modulating key biomarkers and microbiota dysbiosis. Manuscripts targeting probiotic strains and doses administered for obesity-related disorders in clinical studies were sought. MEDLINE, Scopus, Web of Science, and Cochrane Library databases were searched using keywords during the last fifteen years up to April 2020. Two independent reviewers screened titles, abstracts, and then full-text papers against inclusion criteria according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. From 549 interventional reports identified, we filtered 171 eligible studies, from which 24 full-text assays were used for calculating intervention total doses (ITD) of specific species and strains administered. Nine of these reports were excluded in the second-step because no specific data on gut microbiota modulation was found. Six clinical trials (CT) and 9 animal clinical studies were retained for analysis of complete outcome prioritized (body mass index (BMI), adiposity parameters, glucose, and plasma lipid biomarkers, and gut hormones). Lactobacillus spp. administered were double compared to Bifidobacterium spp.; Lactobacillus as single or multispecies formulations whereas most Bifidobacteria only through multispecies supplementations. Differential factors were estimated from obese populations' vs. obesity-induced animals: ITD ratio of 2 × 106 CFU and patterns of administrations of 11.3 weeks to 5.5 weeks, respectively. Estimation of overall probiotics impact from selected CT was performed through a random-effects model to pool effect sizes. Comparisons showed a positive association between the probiotics group vs. placebo on the reduction of BMI, total cholesterol, leptin, and adiponectin. Moreover, negative estimation appeared for glucose (FPG) and CRP. While clinical trials including data for positive modulatory microbiota capacities suggested that high doses of common single and multispecies of Lactobacillus and Bifidobacterium ameliorated key obesity-related parameters, the major limitation was the high variability between studies and lack of standardized protocols. Efforts in solving this problem and searching for next-generation probiotics for obesity-related diseases would highly improve the rational use of probiotics.