Microbiota metabolism of intestinal amino acids impacts host nutrient homeostasis and physiology.

TitleMicrobiota metabolism of intestinal amino acids impacts host nutrient homeostasis and physiology.
Publication TypeJournal Article
Year of Publication2024
AuthorsLi, T-T, Chen, X, Huo, D, Arifuzzaman, M, Qiao, S, Jin, W-B, Shi, H, Li, XV, Iliev, ID, Artis, D, Guo, C-J
Corporate AuthorsJRI Live Cell Bank Consortium
JournalCell Host Microbe
Date Published2024 Apr 22
ISSN1934-6069
Abstract

The intestine and liver are thought to metabolize dietary nutrients and regulate host nutrient homeostasis. Here, we find that the gut microbiota also reshapes the host amino acid (aa) landscape via efficiently metabolizing intestinal aa. To identify the responsible microbes/genes, we developed a metabolomics-based assay to screen 104 commensals and identified candidates that efficiently utilize aa. Using genetics, we identified multiple responsible metabolic genes in phylogenetically diverse microbes. By colonizing germ-free mice with the wild-type strain and their isogenic mutant deficient in individual aa-metabolizing genes, we found that these genes regulate the availability of gut and circulatory aa. Notably, microbiota genes for branched-chain amino acids (BCAAs) and tryptophan metabolism indirectly affect host glucose homeostasis via peripheral serotonin. Collectively, at single-gene level, this work characterizes a microbiota-encoded metabolic activity that affects host nutrient homeostasis and provides a roadmap to interrogate microbiota-dependent activity to improve human health.

DOI10.1016/j.chom.2024.04.004
Alternate JournalCell Host Microbe
PubMed ID38657606