1344-P: Multiomic Signatures of Gut Dysbiosis and Diabetes in HIV Infection

Introduction: Gut dysbiosis has been linked with HIV infection and diabetes. But multiomic signatures of the gut dysbiosis and diabetes in the context of HIV infection remain unknown.

Methods: We examined associations of 97 core gut bacteria genera, 378 plasma metabolites, and 74 serum proteins with prevalent diabetes in 493 women (146 with diabetes; 68% HIV+) of the Women's Interagency HIV Study from 2017 to 2019.

Results: After multivariable adjustment and correction for multiple comparison (FDR < 0.1), we identified 3 genera (Adlercreutzia, Intestinibacter, and Ruminococcus) inversely and 4 genera (Shigella, Escherichia, Megasphaera, and Lactobacillus) positively associated with diabetes. Meanwhile, 76 metabolites, including 2 microbial metabolites (phenylacetylglutamine [PAG] and imidazole-propionate [IMP]) and multiple lipid species (e.g., diradylglycerols [DGs]), and 18 proinflammatory proteins were associated with diabetes. Many metabolites and proteins were associated with the identified diabetes-related gut bacteria. Potential mediation effects of these metabolites and proteins (PAG, IMP, IL-18R1, CD6, OSM, and OPG) on the bacteria-diabetes associations were observed (mediation effects of multiple mediators ranged from 25% for Intestinibacter to 67% for Escherichia). Compared to women without HIV, those with HIV had similar abundances of the identified bacteria but higher circulating levels of many diabetes-related metabolites (PAG, IMP, and several DGs) and proteins (OSM and CD6). The associations of these multiomic features with diabetes tended to be independent of HIV status with little evidence for effect modification by HIV.

Conclusion: Among women with and without HIV, this study identified multiple gut bacteria and circulating metabolites and inflammatory proteins associated with diabetes. The observed bacteria-diabetes associations were partially explained by some microbial metabolites and proinflammatory proteins.