Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA.
Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Friedman Center for Nutrition and Inflammation, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA.
Cell Host Microbe. 2024 May 8;32(5):661-675.e10. doi: 10.1016/j.chom.2024.04.004. Epub 2024 Apr 23.
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.
肠道和肝脏被认为可以代谢膳食营养素并调节宿主的营养稳态。在这里，我们发现肠道微生物组还可以通过有效代谢肠道氨基酸（aa）来重塑宿主的氨基酸（aa）景观。为了确定负责的微生物/基因，我们开发了一种基于代谢组学的测定法来筛选 104 种共生菌，并鉴定出能有效利用 aa 的候选菌。利用遗传学，我们在系统发育上多样化的微生物中鉴定出多个负责代谢的基因。通过用野生型菌株及其在单个 aa 代谢基因上缺失的同基因突变体定植无菌小鼠，我们发现这些基因调节肠道和循环中 aa 的可用性。值得注意的是，微生物组中用于支链氨基酸（BCAAs）和色氨酸代谢的基因通过外周 5-羟色胺间接影响宿主的葡萄糖稳态。总的来说，在单基因水平上，这项工作描述了一种由微生物组编码的代谢活性，它影响宿主的营养稳态，并为研究依赖微生物组的活性以改善人类健康提供了一个路线图。
