153-OR: Gut Microbiota, Blood Metabolome, and Incident Type 2 Diabetes in U.S. Hispanics

Introduction & Objective: Current evidence on the relationship between the human gut microbiota and incident type 2 diabetes (T2D) is limited. We sought to identify gut bacteria and related blood metabolites associated with incident T2D. Methods: Using gut microbiome data from the Hispanic Community Health Study/Study of Latinos (HCHL/SOL), we assessed the associations of bacteria species (spp.) with incident T2D (n=1877; 245 incident cases). In a subset of HCHS/SOL (n=804), we examined cross-sectional associations between species and plasma metabolites. In a larger subset of HCHS/SOL (n=4725), we evaluated associations of identified microbial-related metabolites with incident T2D. Results: We identified 19 out of 516 predominant bacteria associated with incident T2D, with the majority showing lower risk, including 3 Akkermansia spp. and 5 Clostridium spp., a group of potentially beneficial bacteria related to insulin/glucose homeostasis. 99 metabolites were associated with the identified T2D-related spp., 41 of which were associated with incident T2D, including many microbial-derived metabolites from aromatic amino acids, bile acids, and branched-chain amino acids. Further analyses with these metabolites as proxies confirmed the observed prospective associations of 10 spp. with T2D. Conclusions: This study supports the potential role of gut microbiota and microbial metabolites in the development of T2D. Disclosure K. Luo: None. B. Peters: None. Z. Wang: None. T. Wang: None. B. Yu: None. E. Boerwinkle: None. C.R. Isasi: None. R. Kaplan: None. Q. Qi: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK119268; R01-DK126698); National Institute on Minority Health and Health Disparities (R01-MD011389); AHA Postdoctoral Fellowship Award (23POST1020455)