Experimental drug reverses severe fatty liver disease by repairing the gut | ScienceDaily

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Experimental drug reverses severe fatty liver disease by repairing the gut

A new experimental drug reversed severe fatty liver disease in animals by repairing the gut, raising hopes for a powerful new treatment for MASH.

Date:<br>July 11, 2026<br>Source:<br>Michigan Medicine - University of Michigan<br>Summary:<br>An experimental drug called DT-109 reversed severe fatty liver disease in animal studies by repairing the gut and preventing harmful toxins from damaging the liver. The discovery could open the door to a new class of treatments for MASH and potentially other diseases tied to gut health.<br>Share:

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A promising experimental drug may offer a new way to treat severe fatty liver disease by repairing the gut rather than targeting the liver alone. Credit: Shutterstock

An experimental drug developed at Michigan Medicine has shown the ability to reverse severe fatty liver disease in animal studies by restoring gut health. The findings, published in The Journal of Clinical Investigation, suggest that targeting the connection between the gut and liver could offer a promising new approach for treating metabolic dysfunction-associated steatohepatitis (MASH).

MASH is a serious form of fatty liver disease that affects about 7% of people worldwide. It can progress to cirrhosis, liver cancer, and liver failure, yet effective treatment options remain limited.

The investigational compound, known as DT-109, is a glycine-based tripeptide. Researchers found that it reversed MASH in animal models by interrupting a harmful biological process linking the gut and liver.

"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, M.D., Ph.D., senior author of the study and Frederick G. L. Huetwell 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."

How Gut Bacteria Can Drive Liver Disease

Earlier studies from Chen's laboratory had already shown that DT-109 could improve MASH in animals. The new research explains how the compound produces those benefits.

The team first identified a major contributor to the disease: an overgrowth of the bacterium Clostridium perfringens, which generates ammonia inside the gut.

High ammonia levels damage the lining of the digestive tract, weakening the intestinal barrier. Once that protective barrier is compromised, harmful microbial products can enter the bloodstream, reach the liver, and trigger inflammatory immune responses, including excessive activation of CD8+ T cells.

Through a series of experiments, the researchers found that DT-109 disrupted this chain of events, helping restore the health of both the gut and the liver.

DT-109 Restores the Gut Barrier

In both mice and nonhuman primates, DT-109 reduced Clostridium perfringens levels and lowered ammonia production in the intestines. As a result, the intestinal barrier became stronger, limiting the movement of harmful substances from the gut into the body.

The results were especially encouraging in nonhuman primates, whose liver biology and gut microbiota more closely resemble those of humans. In these animals, DT-109 reduced liver inflammation and significantly improved the severity of MASH.

"DT-109 connects microbiota modulation with liver protection by restoring gut barrier integrity and limiting the systemic translocation of ammonia and other pro-inflammatory microbial products within the gut-liver axis," said Jifeng Zhang, Ph.D., co-author and research professor of cardiovascular medicine at U-M Medical School.

"We also found that DT-109 primarily acts in the gastrointestinal tract, but its reach stretches much further."

Potential Benefits Beyond MASH

The researchers believe DT-109 may have uses beyond treating fatty liver disease.

Previous studies have shown that the compound can reduce the formation of atherosclerosis plaques and prevent vascular calcification in nonhuman primates, suggesting it could also become a treatment for cardiovascular disease.

Because breakdown of the intestinal barrier has also been linked to several digestive disorders, the team believes DT-109 could eventually be explored as a treatment for conditions such as inflammatory bowel disease (IBD).

Future research will focus on additional testing needed to move DT-109 into clinical trials and evaluate its safety and effectiveness in people.

"This study presents novel evidence about the pathogenesis of MASH and provides excitement about a therapeutic avenue to explore for a condition that remains difficult to treat," said Elliot Tapper, M.D., Academic Director of...