Novel Findings of the Association Between Gut Microbiota-Derived Metabolite Trimethylamine N- Oxide and Inflammation: Results From a Systematic Review and Dose-Response Meta-Analysis

The gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) has been regarded as one of the potent risk factors of cardiovascular events and diabetes. However, its association with possible inflammatory mediators has not been revealed yet. In the current meta-analysis, we quantitatively summarized the results of studies regarding the association between TMAO and inflammation. Electronic databases including PubMed, ProQuest, Scopus, and Embase were systematically searched and a total of 586 manuscripts were retrieved. After removing 223 duplicates, 363 manuscripts were reviewed. All of the studies regarding the association between TMAO and inflammatory factors were included in the systematic review and eligible studies were included in to the meta-analysis. Accordingly, 13,783 number of participants were included and the results showed that being in the highest category of TMAO Accordingly was associated with 0.27 mg/L (weighted mean difference: 0.268; 95% confidence interval [CI]: 0.058-0.479; p = 0.013) increase in CRP concentrations compared with lowest category. The results of subgrouping and meta-regression revealed the location, CRP sample source, disease status, male percent, proportion of diabetes and smoking as the source of heterogeneity. Moreover, the dose-response meta-analysis revealed a non-linear association between increased TMAO concentrations and increased CRP concentrations (p for nonlinearity = 0.015). To our knowledge, this is first dose-response meta-analysis that summarized the results of studies about the association between circulating TMAO concentrations and inflammation risk.

Keywords: C-reactive-protein; dose-response meta-analysis; gut microbiota metabolite; inflammation; risk factor; trimethylamine N-oxide (TMAO).