ArticleThe Journal of clinical investigation2026
Ammonia in the crosshairs: microbial targets for metabolic dysfunction-associated steatohepatitis prevention.
Article in The Journal of clinical investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Metabolic dysfunction-associated steatohepatitis (MASH) is increasingly linked to disruptions of the gut/liver axis, yet the microbial mechanisms driving disease progression remain incompletely defined. Here, Qu et al. have identified ileal microbial ammonia production by Clostridium perfringens as a mechanistic driver of epithelial barrier dysfunction and hepatic CD8+ T cell remodeling in MASH. In nonhuman primate and mouse models of MASH, the authors demonstrated that the glycine-based tripeptide DT-109 restored gut barrier integrity and attenuated FosB-mediated CCL5 expression in CD8+ T cells via inhibition of bacterial nitrite reductase A-mediated microbial ammonia production. These findings position microbial nitrogen metabolism as a tractable therapeutic target and highlight metabolite-focused microbiome interventions as a potential MASH intervention.
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