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Updated: Jul 2, 2026

Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis
08:58

Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis

Published on: March 11, 2017

Ammonia in the crosshairs: microbial targets for metabolic dysfunction-associated steatohepatitis prevention

Vanessa A Leone1, Arion Kennedy2

  • 1Department of Animal & Dairy Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.

The Journal of Clinical Investigation
|July 1, 2026
PubMed

Insights

Microbial ammonia production by Clostridium perfringens drives metabolic dysfunction-associated steatohepatitis (MASH). A novel peptide therapy targeting this pathway restored gut barrier integrity and modulated T cell responses in MASH models.

Area of Science:

  • Microbiology
  • Hepatology
  • Immunology

Background:

  • Metabolic dysfunction-associated steatohepatitis (MASH) pathogenesis involves gut-liver axis disruptions.
  • Specific microbial mechanisms driving MASH progression are not fully understood.

Purpose of the Study:

  • To elucidate the role of ileal microbial ammonia production in MASH.
  • To investigate the therapeutic potential of targeting microbial nitrogen metabolism.

Main Methods:

  • Utilized nonhuman primate and mouse models of MASH.
  • Investigated the effects of the glycine-based tripeptide DT-109.
  • Assessed gut barrier integrity, CD8+ T cell remodeling, and microbial ammonia production.

Main Results:

  • Identified Clostridium perfringens-derived ammonia as a driver of MASH-associated epithelial barrier dysfunction.
  • DT-109 restored gut barrier integrity in MASH models.
  • DT-109 attenuated CD8+ T cell responses by inhibiting bacterial nitrite reductase A and ammonia production.

Conclusions:

  • Microbial nitrogen metabolism, specifically ammonia production, is a key factor in MASH.
  • Metabolite-focused microbiome interventions targeting ammonia production represent a promising therapeutic strategy for MASH.

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