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)

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.