Project Grant K23DK149857

The National Institute of Diabetes and Digestive and Kidney Diseases awarded The Regents of the University of California, San Francisco $194,076 on September 1, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847).

The award funds a multi-omic investigation of the gut-liver axis in HIV-related liver disease. The project will define mechanistic and biomarker pathways along the gut-liver axis that contribute to and predict hepatic fibrosis in people with HIV, potentially enabling improved risk stratification and targeted intervention. Three research aims will pursue this objective. Aim 1 will define stool microbiome features associated with prevalent fibrosis and predictive of incident fibrosis using 16S rRNA sequencing, confirmatory metagenomics, and longitudinal vibration-controlled transient elastography. Aim 2 will identify DNA methylation signatures associated with prevalent and incident fibrosis in people with HIV using epigenome-wide association analyses of peripheral blood mononuclear cells, as well as targeted pathway analyses focused on gut-liver processes. Aim 3 will conduct a pilot multi-omic study of gut tissue, integrating mucosal metagenomics with single-nucleus transcriptomic and chromatin analysis. The project leverages the MACS/WIHS Combined Cohort Study.

Work is performed in San Francisco, California. The period of performance runs from September 1, 2026, through May 31, 2031. The assistance type is a Project Grant.