Project Grant K99AT013873

The National Center for Complementary and Integrative Health, part of the Department of Health and Human Services National Institutes of Health, awarded The Leland Stanford Junior University $128,695 on July 20, 2026, under the Research and Training in Complementary and Integrative Health program (CFDA 93.213).

The project investigates how gut-derived microbial metabolites regulate host energy metabolism, with focus on the mechanistic basis for cross-kingdom metabolic interactions relevant to obesity, type-2 diabetes, and other metabolic diseases. The research uses high-throughput survival assays, untargeted metabolomics, mathematical modeling, and in silico screening of ligand-receptor interactions to systematically uncover how microbial metabolites act as endocrine effectors of host energy metabolism. During the K99 phase, the recipient will employ computational ligand-receptor screening to identify candidate GPCRs predicted to bind lactic acid produced by Lactiplantibacillus plantarum and perform loss-of-function genetic tests to validate their role in enhanced oxidative phosphorylation and starvation survival. The work will profile microbe-derived metabolite profiles from an array of human-derived and environmental commensals using untargeted metabolomics and correlate metabolite abundance with host survival phenotypes to identify novel metabolic effectors. During the R00 phase, the recipient will expand in silico prediction of ligand-receptor interactions to candidate metabolites identified in the K99 phase and determine their mechanisms of action through targeted genetic knockouts, phosphoproteomic mapping, and transcriptomic analyses to delineate downstream signaling cascades.

Performance is at Palo Alto, California. The award period extends through June 30, 2028.