Title |
The human symbiont Bacteroides thetaiotaomicron promotes diet-induced obesity by regulating host lipid metabolism |
Author |
Sang-Hyun Cho, Yong-Joon Cho, and Joo-Hong Park* |
Address |
School of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul 08826, Republic of Korea |
Bibliography |
Journal of Microbiology, 60(1),118-127, 2022,
|
DOI |
10.1007/s12275-022-1614-1
|
Key Words |
Bacteroides thetaiotaomicron, obesity, lipase,
ANGPTL4, hepcidin |
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. |