Michigan Medicine DT-109 reverses fatty liver in animals
An experimental tripeptide compound known as DT-109 reversed metabolic dysfunction-associated steatohepatitis in animal models by repairing the gut lining and reducing harmful bacterial growth, according to findings published in The Journal of Clinical Investigation.
Key Clinical Takeaways:
- DT-109 is a glycine-based tripeptide developed at Michigan Medicine that treats fatty liver disease by targeting the gut-liver axis.
- Animal studies in mice and nonhuman primates demonstrated that the compound lowers gut levels of Clostridium perfringens and ammonia, strengthening the intestinal barrier.
- The treatment remains experimental, with human clinical trials required to evaluate safety and efficacy in patients.
Michigan Medicine Development Targets the Gut-Liver Axis
Metabolic dysfunction-associated steatohepatitis affects approximately 7% of the global population. The severe form of fatty liver disease causes excess fat accumulation in the liver, leading to inflammation, cellular damage, and potential progression to cirrhosis, liver cancer, and liver failure. Effective therapies remain limited despite recent clinical improvements. Researchers at the University of Michigan Medical School investigated DT-109 to understand how a compound acting primarily within the gastrointestinal tract could alter liver pathology. “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,” 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, stated.
Bacterial Overgrowth and Ammonia Production Drive Liver Damage
The research team confirmed that excessive growth of Clostridium perfringens inside the intestines produces ammonia, which damages the gut’s protective inner lining. As this barrier weakens, microbial toxins escape into the bloodstream and travel to the liver. This translocation triggers inflammation and overactivation of CD8+ T cells, worsening liver injury. Through experiments in mice and nonhuman primates, scientists observed that DT-109 reduced Clostridium perfringens levels, lowered intestinal ammonia production, and reinforced the gut barrier. “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,” Jifeng Zhang, Ph.D., co-author and research professor of cardiovascular medicine at U-M Medical School, explained. Nonhuman primates showed reduced liver inflammation and less severe MASH following treatment, offering data from species with gut microbial communities and liver biology closer to humans.
Broader Metabolic Implications and Next Steps for Human Trials
Beyond liver disease, prior studies demonstrate that DT-109 reduces atherosclerotic plaques and prevents vascular calcification in nonhuman primates. Researchers are also examining whether the compound could benefit patients with inflammatory bowel disease, including Crohn’s disease and ulcerative colitis, due to its barrier-protecting properties. However, the compound has not yet been tested in humans for safety or efficacy. “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,” Elliot Tapper, M.D., Academic Director of Hepatology at Michigan Medicine, noted. Future research will focus on further evaluation of the compound, with the goal of advancing it toward clinical trials.
Disclaimer: The information provided in this article is for educational and scientific communication purposes only and does not constitute medical advice. Always consult with a qualified healthcare provider regarding any medical condition, diagnosis, or treatment plan.