4.7 Article

The gut bacterium Extibacter muris produces secondary bile acids and influences liver physiology in gnotobiotic mice

期刊

GUT MICROBES
卷 13, 期 1, 页码 1-21

出版社

TAYLOR & FRANCIS INC
DOI: 10.1080/19490976.2020.1854008

关键词

Lipids; bile acids; gut microbiota; synthetic community; Extibacter muris; 7α -dehydroxylation; gut-liver axis

资金

  1. German Research Foundation (DFG) [403224013 - SFB 1382]
  2. DFG [INST 95/1528 - SFB 1371]
  3. Nebraska Food for Health Center
  4. National Cancer Institute [1RO1 CA204808-01]
  5. USDA Hatch [ILLU-538-916]
  6. Illinois Campus Research Board [RB18068]
  7. David H. and Norraine A. Baker Graduate Fellowship in Animal Sciences

向作者/读者索取更多资源

Extibacter muris, a newly described mouse gut bacterium, produces secondary bile acids in vivo that affect the liver proteomes. It has minor effects on the Oligo-MM12 community under a high-fat diet, but does not influence body weight and other physiological parameters.
Extibacter muris is a newly described mouse gut bacterium which metabolizes cholic acid (CA) to deoxycholic acid (DCA) via 7 alpha-dehydroxylation. Although bile acids influence metabolic and inflammatory responses, few in vivo models exist for studying their metabolism and impact on the host. Mice were colonized from birth with the simplified community Oligo-MM12 with or without E. muris. As the metabolism of bile acids is known to affect lipid homeostasis, mice were fed either a low- or high-fat diet for eight weeks before sampling and analyses targeting the gut and liver. Multiple Oligo-MM12 strains were capable of deconjugating primary bile acids in vitro. E. muris produced DCA from CA either as pure compound or in mouse bile. This production was inducible by CA in vitro. Ursodeoxycholic, chenodeoxycholic, and beta-muricholic acid were not metabolized under the conditions tested. All gnotobiotic mice were stably colonized with E. muris, which showed higher relative abundances after HF diet feeding. The presence of E. muris had minor, diet-dependent effects on Oligo-MM12 communities. The secondary bile acids DCA and surprisingly LCA and their taurine conjugates were detected exclusively in E. muris-colonized mice. E. muris colonization did not influence body weight, white adipose tissue mass, liver histopathology, hepatic aspartate aminotransferase, or blood levels of cholesterol, insulin, and paralytic peptide (PP). However, proteomics revealed shifts in hepatic pathways involved in amino acid, glucose, lipid, energy, and drug metabolism in E. muris-colonized mice. Liver fatty acid composition was substantially altered by dietary fat but not by E. muris.In summary, E. muris stably colonized the gut of mice harboring a simplified community and produced secondary bile acids, which affected proteomes in the liver. This new gnotobiotic mouse model can now be used to study the pathophysiological role of secondary bile acids in vivo.

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