A potential new treatment for metabolic dysfunction-associated steatohepatitis (MASH) works by improving gut health rather than targeting the liver directly, according to research published in The Journal of Clinical Investigation.
Researchers at Michigan Medicine found that the glycine-based tripeptide DT-109 reversed MASH in animal models by disrupting a disease-driving pathway linking the gut and liver. MASH affects approximately 7% of the global population and can progress to cirrhosis, liver cancer, and liver failure. Treatment options remain limited despite recent therapeutic advances.
The study identified a key driver of MASH: the proliferation of the bacterium Clostridium perfringens, which produces ammonia in the gut. Elevated ammonia levels erode the digestive tract’s inner lining and weaken the intestinal barrier, allowing harmful toxins to reach the liver and trigger inflammatory immune responses.
Through experiments in mice and non-human primates, the research team found that DT-109 interrupted this process. The compound diminished Clostridium perfringens populations and reduced intestinal ammonia production, strengthening the intestinal barrier. In non-human primates, whose livers and gut microbiota more closely resemble those of humans, DT-109 reduced liver inflammation and MASH severity.
Senior author Dr Eugene Chen noted clear evidence that DT-109 protects the gut epithelial barrier, reducing the systemic influx of harmful microbial products thought to contribute to MASH development and progression.
The researchers suggest DT-109’s benefits may extend beyond MASH. Previous studies have shown the compound can limit atherosclerosis plaque formation and vascular calcification, positioning it as a potential treatment for cardiovascular disease. Because intestinal barrier dysfunction is implicated in several gastrointestinal disorders, the team believes DT-109 could eventually have applications in conditions such as inflammatory bowel disease.
Source: News Medical / University of Michigan (Journal of Clinical Investigation, 2026)
