Host hepatic metabolism is modulated by gut microbiota-derived sphingolipids

被引:43
作者
Le, Henry H. [1 ]
Lee, Min-Ting [1 ]
Besler, Kevin R. [1 ]
Johnson, Elizabeth L. [1 ]
机构
[1] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA
基金
美国国家卫生研究院;
关键词
HOMEOSTASIS; PHYSIOLOGY; ACIDS;
D O I
10.1016/j.chom.2022.05.002
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Microbially-derived gut metabolites are important contributors to host phenotypes, many of which may link microbiome composition to metabolic disease. However, relatively few metabolites with known bioactivity have been traced from specific microbes to host tissues. Here, we use a labeling strategy to characterize and trace bacterial sphingolipids from the gut symbiont Bacteroides thetaiotaomicron to mouse colons and livers. We find that bacterial sphingolipid synthesis rescues excess lipid accumulation in a mousemodel of hepatic steatosis and observe the transit of a previously uncharacterized bacterial sphingolipid to the liver. The addition of this sphingolipid to hepatocytes improves respiration in response to fatty-acid overload, suggesting that sphingolipid transfer to the liver could potentially contribute to microbiota-mediated liver function. This work establishes a role for bacterial sphingolipids in modulating hepatic phenotypes and defines a workflow that permits the characterization of other microbial metabolites with undefined functions in host health.
引用
收藏
页码:798 / +
页数:18
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