Effect of traditional Chinese medicine on gut microbiota in adults with type 2 diabetes: A systematic review and meta-analysis

Background: Despite advances in research on type 2 diabetes mellitus (T2DM) with the development of science and technology, the pathogenesis and treatment response of T2DM remain unclear. Recent studies have revealed a significant role of the microbiomein the development of T2DM, and studies have found that the gut microbiota may explain the therapeutic effect of traditional Chinese medicine (TCM), a primary branch of alternative and complementary medicine, in the treatment of T2DM. The aim of this study was to systematically review all randomized controlled trials (RCTs) on TCM for gut microbiota to assess the effectiveness and safety of TCM in T2DM patients. Methods: All RCTs investigating the effects of TCM interventions on modulating gut microbiota and improving glucose metabolism in the treatment of T2DM adults were included. Meta-analyses were conducted when sufficient data were available, other results were reported narratively. The study protocol was pre-specified, documented, and published in PROSPERO (registration no. CRD42020188043). Results: Five studies met the eligibility criteria of the systematic review. All five studies reported the effects of TCM interventions on the gut microbiota modulation and blood glucose control. There were statistically significant improvements in HbA1c (mean difference [MD]: -0.69%; [95% CI -0.24, -0.14]; p = 0.01, I-2 = 86%), fasting blood glucose (MD: -0.87 mmol/l; [95% CI -1.26, -0.49]; p < 0.00001, I-2 = 75%) and 2-h postprandial blood glucose(MD: -0.83mmol/l; [95% CI: -1.01, -0.65]; p < 0.00001, I-2 = 0%). In addition, there were also statistically significant improvements in homeostasis model assessment of insulin resistance (HOMA-IR) (standardized mean difference [SMD]: -0.99, [95% CI -1.25 to -0.73]; p < 0.00001, I-2 = 0%) and homeostasis model assessment of beta-cell function (HOMA-beta) (SMD: 0.54, [95% CI 0.21 to 0.87]; p = 0.001, I-2 = 0%).There was a significant change in the relative abundance of bacteria in the genera Bacteroides (standardized mean difference [SMD] 0.87%; [95% CI 0.58, 1.16], however, the change in Enterococcus abundance was not statistically significant (SMD: -1.71%; [95% CI: -3.64, 0.23]; p = 0.08) when comparing TCM supplementaltreatment with comparator groups. Other changes in the gut microbiota, including changes in the relative abundances of some probiotics and opportunistic pathogens at various taxon levels, and changes in diversity matrices (alpha and beta), were significant by narrative analysis. However, insufficient evidences were found to support that TCM intervention had an effect on inflammation. Conclusion: TCM had the effect of modulating gut microbiota and improving glucose metabolisms in T2DM patients. Although the results of the included studies are encouraging, further well-conducted studies on TCM interventions targeting the gut microbiota are needed.