A liver drug that works in the gut
An experimental compound developed at Michigan Medicine reversed a severe form of fatty liver disease in animal studies by acting on the gut rather than the liver itself. The drug, known as DT-109, is a glycine-based tripeptide, a small molecule built from three amino acids.
The findings were published in The Journal of Clinical Investigation. In the studies, DT-109 reduced harmful gut bacteria, protected the intestinal lining and limited the flow of inflammatory microbial products into the bloodstream, where they reach the liver.
What MASH does
Metabolic dysfunction-associated steatohepatitis, or MASH, affects roughly 7% of the world's population. Fat accumulates in the liver, causing inflammation and cell damage, and over time the condition can progress to cirrhosis, liver cancer and liver failure.
Treatment options have improved in recent years but remain limited. The Michigan team had already shown that DT-109 improved MASH in animals. What was missing was an explanation of how it worked.
"We see clear evidence that DT-109 protects the gut epithelial barrier, reducing the systemic influx of harmful microbial products that are thought to contribute to MASH development and progression," said Eugene Chen, senior author and a professor of cardiovascular medicine at the University of Michigan Medical School. "This compound shows benefits to the gastrointestinal system and has great potential as a treatment for MASH."
Why the gut route matters
The gut-liver connection has become one of the busier areas in liver research. Bacterial products that leak through a damaged intestinal barrier trigger immune responses in the liver, and that inflammation is part of what turns simple fat accumulation into MASH.
Targeting the barrier instead of the liver could avoid some of the side effects that come with drugs acting directly on liver metabolism. The results so far are in animals, and human trials would be needed before any of this reaches patients. The authors say the mechanism also has implications for cardiovascular disease, where the same microbial products are under study.