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Bile acids as metabolic regulators.

Tiangang Li1, John Y L Chiang

  • 1aDepartment of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, Kansas bDepartment of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, USA.

Current Opinion in Gastroenterology
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Summary
This summary is machine-generated.

New research reveals how gut microbiota and bile acid signaling impact metabolism. Targeting these pathways offers a promising strategy for treating obesity and type 2 diabetes.

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Area of Science:

  • Metabolic research
  • Gut-liver axis
  • Microbiome science

Background:

  • Bile acid synthesis is regulated by negative feedback mechanisms.
  • Enterohepatic bile acid signaling influences metabolic homeostasis.
  • Gut microbiota interactions are crucial for metabolic health.

Purpose of the Study:

  • To review the molecular mechanisms of intestine-liver bile acid signaling and gut microbiota.
  • To understand their impact on lipid, glucose, and energy metabolism.
  • To explore therapeutic strategies for metabolic diseases.

Main Methods:

  • Review of recent scientific literature.
  • Analysis of molecular mechanisms.
  • Investigation of signaling pathways (FXR, FGF15/19).

Main Results:

  • A positive feedback loop involving intestinal FXR antagonism links gut microbiota to bile acid regulation.
  • Novel regulators (Diet1, SHP-2) of bile acid synthesis via the gut-liver FXR-FGF axis identified.
  • Enhanced distal ileum and colon bile acid signaling contributes to metabolic benefits of bariatric surgery and bile acid sequestrants.

Conclusions:

  • Small-molecule ligands targeting TGR5 and FXR show therapeutic potential for metabolic and inflammatory diseases.
  • Targeting enterohepatic circulation modulates gut-liver bile acid signaling, incretin production, and microbiota.
  • This approach offers a new strategy for treating obesity and type 2 diabetes.