Researchers have found that a potential drug developed at the Michigan Medical Society could treat severe fatty liver disease by improving gut health, according to a study published in . clinical research journal.
Glycine-based tripeptide DT-109 reversed metabolic dysfunction-associated steatohepatitis (MASH) in an animal model by disrupting the disease-causing pathway connecting the intestine and liver.
MASH affects approximately 7% of the world’s population and can lead to cirrhosis, liver cancer, and liver failure. Despite recent therapeutic advances, treatment options remain limited.
There is clear evidence that DT-109 protects the intestinal epithelial barrier and reduces the systemic influx of harmful microbial products that are thought to contribute to the development and progression of MASH. ”
Eugene Chen, M.D., senior author of the study and Frederick G.L. Heutwell Professor of Cardiovascular Medicine at the University of Michigan School of Medicine
“This compound shows benefits for the gastrointestinal system and has great potential as a treatment for MASH.”
Previous animal studies by Chen’s team had shown that DT-109 may work as a treatment for MASH, but researchers are now understanding the mechanisms behind its therapeutic effects.
Before testing the compound, Chen’s team first checked for bacterial growth, a key factor in MASH. Clostridium perfringenswhich produces ammonia in the intestines.
Elevated ammonia levels erode the lining of the gastrointestinal tract, weakening the intestinal barrier and allowing harmful toxins to reach the liver and trigger an inflammatory immune response, including overactivation of CD8+ T cells.
Through a series of experiments, Chen’s team discovered that DT-109 disrupts this process and restores the integrity of both the intestines and liver.
compounds are reduced Clostridium perfringens Mice and non-human primates produce intestinal ammonia, which strengthens the intestinal barrier.
In non-human primates, whose liver and gut microbiota more closely resemble those of humans, DT-109 reduced liver inflammation and the severity of MASH.
“DT-109 couples microbiota regulation and liver protection by restoring the integrity of the intestinal barrier and limiting the systemic translocation of ammonia and other pro-inflammatory microbial products within the gut-liver axis,” said Dr. Jifeng Zhang..co-author and research professor of cardiovascular medicine at the UM School of Medicine.
“We also found that DT-109 primarily acts in the gastrointestinal tract, but its range is broader.”
Researchers say the study results suggest the benefits of DT-109 may extend beyond MASH.
DT-109 has been shown to limit atherosclerotic plaque formation and stop vascular calcification in non-human primates, positioning it as a potential treatment for cardiovascular disease.
Because intestinal barrier dysfunction is associated with several gastrointestinal disorders, the research team believes DT-109 may eventually have application in diseases such as inflammatory bowel disease (IBD).
Future research will focus on further evaluating DT-109 to advance the compound into clinical trials to assess safety and efficacy in humans.
“This study provides new evidence about the pathogenesis of MASH and provides excitement about treatments exploring a condition that remains difficult to treat,” said Elliott Tapper, MD, academic director of hepatology at the University of Michigan School of Medicine.
“What MASH patients need are safe and effective treatments that can improve liver and heart health. Of course, we are excited about these developments.”
sauce:
Michigan Medicine – University of Michigan
References:
Koo, P. others. (2026). Metabolic dysfunction-related steatohepatitis exacerbated by ammonia from Clostridium perfringens is attenuated by the tripeptide DT-109. Clinical Research Journal. DOI: 10.1172/JCI200522. https://www.jci.org/articles/view/200522
