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Smith SA , Ogawa SA , Chau L , Whelan KA , Hamilton KE , Chen J , Tan L , Chen EZ , Keilbaugh S , Fogt F , Bewtra M , Braun J , Xavier RJ , Clish CB , Slaff B , Weljie AM , Bushman FD , Lewis JD , Li H , Master SR , Bennett MJ , Nakagawa H , Wu GD
Mitochondrial dysfunction in inflammatory bowel disease alters intestinal epithelial metabolism of hepatic acylcarnitines
J Clin Invest. 2021 Jan 4;131(1)
PMID: 33141762    PMCID: PMC7773399    URL: https://www.ncbi.nlm.nih.gov/pubmed/33141762
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As the interface between the gut microbiota and the mucosal immune system, there has been great interest in the maintenance of colonic epithelial integrity through mitochondrial oxidation of butyrate, a short-chain fatty acid produced by the gut microbiota. Herein, we showed that the intestinal epithelium could also oxidize long-chain fatty acids, and that luminally delivered acylcarnitines in bile could be consumed via apical absorption by the intestinal epithelium, resulting in mitochondrial oxidation. Finally, intestinal inflammation led to mitochondrial dysfunction in the apical domain of the surface epithelium that may reduce the consumption of fatty acids, contributing to higher concentrations of fecal acylcarnitines in murine Citrobacter rodentium-induced colitis and human inflammatory bowel disease. These results emphasized the importance of both the gut microbiota and the liver in the delivery of energy substrates for mitochondrial metabolism by the intestinal epithelium.
1558-8238 Smith, Sarah A Ogawa, Sayaka A Chau, Lillian Whelan, Kelly A Hamilton, Kathryn E Chen, Jie Tan, Lu Chen, Eric Z Keilbaugh, Sue Fogt, Franz Bewtra, Meenakshi Braun, Jonathan Xavier, Ramnik J Clish, Clary B Slaff, Barry Weljie, Aalim M Bushman, Frederic D Lewis, James D Li, Hongzhe Master, Stephen R Bennett, Michael J Nakagawa, Hiroshi Wu, Gary D K01 DK103953/DK/NIDDK NIH HHS/United States R03 DK114463/DK/NIDDK NIH HHS/United States K01 DK100485/DK/NIDDK NIH HHS/United States P30 DK050306/DK/NIDDK NIH HHS/United States R01 DK114436/DK/NIDDK NIH HHS/United States R01 GM103591/GM/NIGMS NIH HHS/United States R01 AA026297/AA/NIAAA NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't J Clin Invest. 2021 Jan 4;131(1):e133371. doi: 10.1172/JCI133371.