Glucose Parameters, Inflammation Markers, and Gut Microbiota Changes of Gut Microbiome-Targeted Therapies in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Purpose This meta-analysis aims to summarize the effects of gut microbiome-targeted therapies (MTTs) on glucometabolic, inflammatory factors and gut microbiota in patients with type 2 diabetes mellitus (T2DM).Methods Four databases were searched for randomized controlled trials (RCTs) that included subjects with T2DM who received MTTs. All results were presented as standardized mean difference (SMD) or mean difference (MD) and 95% CIs. In addition, subgroup analyses were performed according to region, type of MTTs, number of probiotic strains, probiotics dose, prebiotics dose, duration of MTTs, mean age, and baseline body mass index.Results A total of 54 RCTs were included, encompassing 60 groups and 3390 subjects. Overall, MTTs intervention decreased fasting plasma glucose (MD = -7.97 mg/dL [95% CI = -10.82, -5.12]; P < .00001), 2-hour postprandial blood glucose (MD = -43.30 mg/dL [95% CI = -75.83, -10.77]; P = .009), fasting insulin (MD = -1.73 uU/mL [95% CI = -2.63, -0.84]; P = .0001), HbA1c (MD = -0.28%, [95% CI = -0.39, -0.17]; P < .00001), and homeostatic model assessment of insulin resistance (MD =-0.53 [95% CI = -0.85, -0.20]; P = .0002). Furthermore, MTTs supplementation reduced high-sensitivity C-reactive protein, tumor necrosis factor alpha, and lipopolysaccharides. Meanwhile, the levels of interleukin-10 were increased. Moreover, the abundance of Actinobacteria, Lactobacillus, and Lactobacillus casei subgroup increased.Conclusion MTTs modestly improved glucometabolic parameters, reduced pro-inflammatory cytokines, and enriched beneficial microbes (eg, Actinobacteria, Lactobacillus) in subjects with T2DM. However, heterogeneity and limited long-term data highlight the need for large-scale RCTs.