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Decoding the Gut-Liver Crosstalk: Microbial Metabolite- Driven AhR Signalling Networks in MASLD Pathogenesis.

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Summary

Gut microbes and their metabolites regulate the aryl hydrocarbon receptor (AhR) to impact metabolic-dysfunction-associated steatotic liver disease (MASLD). Targeting this gut-liver axis offers new therapeutic strategies for MASLD.

Keywords:
Aryl hydrocarbon receptorGut microbiotaMetabolic dysfunction-associated steatotic liver diseaseMetabolitesNatural products

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Area of Science:

  • Hepatology
  • Microbiology
  • Immunology

Background:

  • Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a growing global health concern linked to obesity and diabetes.
  • The gut microbiota plays a crucial role in MASLD development and presents potential therapeutic targets.

Purpose of the Study:

  • To propose and review the
  • gut microbiota-metabolite-AhR-MASLD
  • axis as a central regulator of liver health.
  • To highlight the role of microbial metabolites and the aryl hydrocarbon receptor (AhR) in MASLD pathogenesis and treatment.

Main Methods:

  • Systematic review of existing literature on gut microbiota, metabolites, AhR signaling, and MASLD.
  • Integration of data on microbial metabolites (tryptophan metabolites, SCFAs) as AhR ligands.
  • Analysis of AhR's role in hepatic non-parenchymal cells and its impact on liver homeostasis.

Main Results:

  • Microbiota-derived metabolites (tryptophan metabolites, SCFAs) act as endogenous AhR ligands.
  • AhR activation by these metabolites exerts hepatoprotective effects by modulating lipid metabolism, inflammation, and immune responses.
  • AhR signaling in non-parenchymal liver cells contributes to anti-inflammatory and anti-fibrotic effects.

Conclusions:

  • The gut microbiota-metabolite-AhR-MASLD axis is a key mediator of gut-liver metabolic communication.
  • Targeting this axis, through microbiota modulation or natural products, offers a promising multi-target therapeutic strategy for MASLD.
  • AhR represents a significant therapeutic target for precision intervention in MASLD.