The Effect of Prebiotics and Oral Anti-Diabetic Agents on Gut Microbiome in Patients with Type 2 Diabetes: A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials.

Background: Nutritional interventions such as the use of prebiotics can promote eubiosis of gut microbiome and maintain glucose homeostasis in patients with type 2 diabetes (T2D). However, it would appear that results of the effects of prebiotics on the community of microbes in the gut are not consistent. Aim: To examine the effect of prebiotics and oral antidiabetic agents on gut microbiome in patients with T2D. Methods: The PRISMA Extension Statement for Systematic Reviews and Network Meta-analyses was used to conduct this review. Searches were carried out in EMBASE, EBSCO-host databases, Google Scholar and the reference lists of articles for studies that are relevant to the research question, from database inception to 15 August 2022. The search strategy was based on PICOS framework. Network Meta-analysis which allows the estimation of relative treatment effects by combing both direct trial evidence (e.g., treatment A vs. treatment B) and indirect evidence was conducted. Furthermore, pairwise meta-analysis was also carried out to estimate effect sizes based on head-to-head comparisons of treatments and/or control conditions. Results: Findings of the Network meta-analysis revealed that prebiotics significantly reduced HbA1c compared with control and the SMD was −0.43 [95% CI, −0.77, −0.08; p = 0.02], whereas there was no significant difference (p > 0.05) between the other treatments and control. In addition, anti-diabetic agents including glipizide and metformin also reduced HbA1C, although these were not significantly different (p > 0.05) from control. While prebiotics promoted Bifidobacterium and Akkermansia, the improvements were not significantly different (p > 0.05) from control. On the other hand, metformin decreased the relative abundance of Bifidobacterium, but increased Lactobacillus and Akkermansia, although the differences were not significant (p > 0.05) compared with control. With respect to fasting blood glucose and BMI, the effects of prebiotics and oral antidiabetic agents did not differ significantly (p > 0.05) from controls. Conclusions: The findings of the systematic review and Network meta-analysis demonstrated prebiotics were significantly (p < 0.05) more effective in reducing HbA1c than control in patients with T2D. However, the effects of prebiotics and oral antidiabetic agents did not differ significantly (p > 0.05) from the controls in relation to fasting blood glucose, post-prandial blood glucose, body mass index and the genera of gut bacteria examined. More studies are required to fully investigate the effects of prebiotics and oral antidiabetic agents in patients with T2D