How a Drug Reverses Severe Fatty Liver Disease by Repairing the Gut

A Gut-Based Approach to MASH

Developed at Michigan Medicine, DT-109 is a glycine-based tripeptide. Researchers reported in The Journal of Clinical Investigation that the compound reversed MASH in animal models by acting primarily in the gastrointestinal system.

MASH affects approximately 7% of the world's population. The disease involves excess fat in the liver, inflammation and cellular damage; it can progress to cirrhosis, liver cancer and liver failure. Effective therapies remain limited.

How Gut Damage Reaches the Liver

The team confirmed that excessive growth of Clostridium perfringens, a bacterium that produces ammonia in the intestines, contributes to MASH. High ammonia levels can damage the gut's protective lining.

When the intestinal barrier weakens, microbial toxins and other substances can enter the bloodstream and reach the liver. There, they can trigger inflammation and excessive activation of CD8+ T cells, immune cells that can worsen liver damage when overactive.

Researchers Describe the Findings

Eugene Chen, the study's senior author and a professor at the University of Michigan Medical School, said DT-109 protects the gut barrier and reduces harmful microbial products entering the body. He said the compound has potential as a MASH treatment. Co-author Jifeng Zhang said DT-109 links changes in gut microbes with liver protection by restoring the barrier and limiting the spread of ammonia and other inflammatory microbial products.