PT  - JOURNAL ARTICLE
AU  - Nick Bohmann
AU  - Tomasz Wilmanski
AU  - Lisa Levy
AU  - Johanna W. Lampe
AU  - Thomas Gurry
AU  - Noa Rappaport
AU  - Christian Diener
AU  - Sean M. Gibbons
TI  - Microbial community-scale metabolic modeling predicts personalized short-chain-fatty-acid production profiles in the human gut
AID  - 10.1101/2023.02.28.530516
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.02.28.530516
4099  - http://biorxiv.org/content/early/2023/03/01/2023.02.28.530516.short
4100  - http://biorxiv.org/content/early/2023/03/01/2023.02.28.530516.full
AB  - Microbially-derived short-chain fatty acids (SCFAs) in the human gut are tightly coupled to host metabolism, immune regulation, and integrity of the intestinal epithelium. However, the production of SCFAs can vary widely between individuals consuming the same diet, with lower levels often associated with disease. A mechanistic understanding of this heterogeneity is lacking. We present a microbial community-scale metabolic modeling (MCMM) approach to predict individual-specific SCFA production profiles. We assess the quantitative accuracy of our MCMMs using in vitro, ex vivo, and in vivo data. Next, we identify associations between MCMM SCFA predictions and a panel of blood-based clinical chemistries in a large human cohort. Finally, we demonstrate how MCMMs can be leveraged to design personalized dietary, prebiotic, and probiotic interventions that optimize SCFA production in the gut. Our results represent an important advance in engineering gut microbiome functional outputs for precision health and nutrition.Competing Interest StatementOne of our coauthors, Dr. Thomas Gurry, works for a commercial prebiotics company (Myota GmbH, Inc.). Myota was not involved in the funding or conduct of this research. The authors report no other conflicts of interest.