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Gut microbiota composition influences bile acid synthesis in the liver. In alcohol consumers, specific gut bacteria may activate hepatic cyclic adenosine monophosphate responsive element-binding protein 3-like protein 3 (CREBH), increasing bile acid production.

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Area of Science:

  • Gastroenterology and Hepatology
  • Microbiology
  • Metabolic Regulation

Background:

  • Alcohol consumption is linked to altered fecal bile acid secretion.
  • The role of hepatic CREBH and gut microbiota in alcohol-induced bile acid changes requires elucidation.

Purpose of the Study:

  • To investigate the impact of gut microbiota composition on bile acid synthesis regulation.
  • To determine if alcohol consumption influences bile acid synthesis via CREBH activation or microbiota alterations.

Main Methods:

  • Humanized germ-free mice models colonized with stool from healthy, cirrhotic, or alcoholic subjects.
  • Analysis of hepatic gene expression for bile acid synthesis enzymes (Cyp7a1, Cyp8b1) and regulatory factors.
  • Assessment of liver and fecal bile acid concentrations and gut microbiota composition (16S rRNA sequencing).

Main Results:

  • Hepatic Cyp7a1 and Cyp8b1 mRNA were induced in mice colonized with healthy or alcoholic microbiota, but not cirrhotic microbiota.
  • Liver bile acid concentrations increased in alcoholic microbiota-colonized mice.
  • Gut microbiota composition in alcoholic and healthy groups showed increased capacity for bile acid deconjugation and 7α-dehydroxylation.

Conclusions:

  • Gut microbiota composition significantly influences the regulation of rate-limiting enzymes in hepatic bile acid synthesis.
  • Specific gut microbial taxa may up-regulate CREBH, thereby inducing bile acid synthesis genes.
  • These findings highlight the interplay between gut microbiota and host metabolism in the context of alcohol consumption.