Gut Microbiota‐Derived Trimethylamine N‐Oxide and the Risk of Diabetes: An Updated Systematic Review and Meta‐Analysis

Recent studies have discovered higher levels of circulating trimethylamine N-oxide, a metabolite produced by gastrointestinal microbiota, among patients diagnosed with diabetes. This study presents an updated systematic review and meta-analysis examining the association between trimethylamine N-oxide levels and the risk of developing diabetes. PubMed and Scopus databases were searched for the studies published up to April 2024. Observational (cross-sectional, case-control, and cohort) studies examining the relationship between TMAO levels and diabetes were included in our systematic review and meta-analysis, excluding non-original research, non-human studies, and non-English publications. Out of 1538 publications, 32 studies focusing on type 2 and gestational diabetes were included. We conducted two distinct meta-analyses investigating the association between TMAO levels and type 2 diabetes. First, we found significantly elevated TMAO levels in diabetic patients compared to non-diabetics (standardized mean difference [SMD]: 1.21, 95% confidence interval [CI]: 0.13-2.28). Second, we observed that elevated TMAO levels were associated with 49% increased odds of diabetes (odds ratio [OR]: 1.49, 95% CI: 1.06-2.10). However, the pooled hazard ratio (HR) analysis did not reveal a statistically significant association (HR: 1.00, 95% CI: 0.62, 1.61). Moreover, the included studies showed a higher type 2 diabetes prevalence in the elevated TMAO group. Regarding gestational diabetes, we also detected a positive correlation with TMAO levels. Our study indicates that individuals with type 2 diabetes have notably higher TMAO levels compared to non-diabetics. Furthermore, our systematic review suggests an elevated risk of developing both type 2 diabetes and gestational diabetes in individuals with higher TMAO levels.