The human symbiont Bacteroides thetaiotaomicron promotes diet-induced obesity by regulating host lipid metabolism

Sang-Hyun Cho; Yong-Joon Cho; Joo-Hong Park

doi:10.1007/s12275-022-1614-1

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The human symbiont Bacteroides thetaiotaomicron promotes diet-induced obesity by regulating host lipid metabolism: Sang-Hyun Cho , Yong-Joon Cho , Joo-Hong Park; Journal of Microbiology 2022;60(1):118-127.
DOI: https://doi.org/10.1007/s12275-022-1614-1
Published online: December 29, 2021

School of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul 08826, Republic of KoreaSchool of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul 08826, Republic of Korea

Corresponding author: Joo-Hong Park ,

Received: 29 November 2021 • Revised: 14 December 2021 • Accepted: 15 December 2021

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Abstract

The gut microbiome plays an important role in lipid metabolism. Consumption of a high-fat diet (HFD) alters the bacterial communities in the gut, leading to metabolic disorders. Several bacterial species have been associated with diet-induced obesity, nonalcoholic fatty liver disease, and metabolic syndrome. However, the mechanisms underlying the control of lipid metabolism by symbiotic bacteria remain elusive. Here, we show that the human symbiont Bacteroides thetaiotaomicron aggravates metabolic disorders by promoting lipid digestion and absorption. Administration of B. thetaiotaomicron to HFD-fed mice promoted weight gain, elevated fasting glucose levels, and impaired glucose tolerance. Furthermore, B. thetaiotaomicron treatment upregulated the gene expression of the fatty acid transporter and increased fatty acid accumulation in the liver. B. thetaiotaomicron inhibits expression of the gene encoding a lipoprotein lipase inhibitor, angiopoietin-like protein 4 (ANGPTL4), thereby increasing lipase activity in the small intestine. In particular, we found that B. thetaiotaomicron induced the expression of hepcidin, the master regulator of iron metabolism and an antimicrobial peptide, in the liver. Hepcidin treatment resulted in a decrease in ANGPTL4 expression in Caco-2 cells, whereas treatment with an iron chelator restored ANGPTL4 expression in hepcidin- treated cells. These results indicate that B. thetaiotaomicron- mediated regulation of iron storage in intestinal epithelial cells may contribute to increased fat deposition and impaired glucose tolerance in HFD-fed mice.

Keywords: colon;inflammation;melatonin;microbiota dysfunction;restraint stress

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The human symbiont Bacteroides thetaiotaomicron promotes diet-induced obesity by regulating host lipid metabolism

J. Microbiol. 2022;60(1):118-127. Published online December 29, 2021

DOI: https://doi.org/10.1007/s12275-022-1614-1

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