Microbial community-scale metabolic modeling predicts personalized short chain fatty acid production profiles in the human gut

Abstract

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 usingin vitro,ex vivo, andin vivodata. 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.

Network analysis of toxin production in Clostridioides difficile identifies key metabolic dependencies

“…CDI is most effectively resolved through fecal microbiota transplants (FMTs) [ 39 ]; however, FMTs are typically only prescribed for patients with severe or recurrent cases of CDI [ 39 ]. Using microbial engineering to design probiotic communities that can be offered as a non-invasive CDI therapeutic is a major advancement already underway within the field [ 40 , 41 ]. An important step in designing these therapeutic communities is identifying reactions or pathways associated with high and low toxin production and understanding how those reactions change as a function of the environment, resulting in specific toxin-associated phenotypes.…”