Gut Microbiota-Derived Tryptophan Metabolites Modulate Inflammatory Response in Hepatocytes and Macrophages
By S. Krishnan, Yufang Ding, N. Saedi, Maria Choi, G. Sridharan, D. Sherr, M. Yarmush, R. Alaniz, A. Jayaraman, Kyongbum Lee. Cell Reports, 2018
600 citations recorded by the source corpus.
SUMMARY The gut microbiota plays a significant role in the progression of fatty liver disease; however, the mediators and their mechanisms remain to be elucidated. Comparing metabolite profile differences between germ-free and conventionally raised mice against differences between mice fed a low- and high-fat diet (HFD), we identified tryptamine and indole-3-acetate (I3A) as metabolites that depend on the microbiota and are depleted under a HFD. Both metabolites reduced fatty-acid- and LPS-stimulated production of pro-inflammatory cytokines in macrophages and inhibited the migration of cells toward a chemokine, with I3A exhibiting greater potency. In hepatocytes, I3A attenuated inflammatory responses under lipid loading and reduced the expression of fatty acid synthase and sterol regulatory element-binding protein-1c. These effects were abrogated in the presence of an aryl-hydrocarbon receptor (AhR) antagonist, indicating that the effects are AhR dependent. Our results suggest that gut microbiota could influence inflammatory responses in the liver through metabolites engaging host receptors.
Subfields: Epidemiology, Molecular Biology, Physiology
View Paper: https://www.semanticscholar.org/paper/bd175345013ea21fddaf6a9242d105fba4672b5b
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In Molecular Biology
Citations in the corpus
- Tryptophan Metabolism: A Link Between the Gut Microbiota and Brain. (2019, background): “For instance, a recent study revealed that a high-fat diet depletes the microbial metabolites IAA and tryptamine in the cecum of mice (64), suggesting that the microbial tryptophan degradation pathway can be attenuated under a high-fat diet.”