A new experimental medicine that works by repairing the gut rather than directly targeting the liver has shown encouraging results against a severe form of fatty liver disease, offering fresh hope for millions of people living with a condition that currently has few effective treatment options.

Researchers at the University of Michigan's Michigan Medicine found that a compound made of glycine called 'DT-109' helped fix metabolic problems related to steatohepatitis (MASH)—a serious type of fatty liver disease that causes inflammation and scarring—in mice and non-human primates. The findings suggest that strengthening the intestine's natural protective lining may also help heal the liver.

MASH affects an estimated 7% of the world's population and can progress to cirrhosis, liver cancer and liver failure. Previous studies in journals like Nature Reviews Gastroenterology & Hepatology and The Lancet Gastroenterology & Hepatology have shown that fatty liver disease is becoming a bigger problem worldwide, mainly due to obesity, type 2 diabetes, and metabolic disorders.

Before testing DT-109, the Michigan team identified a key culprit inside the gut. Laboratory experiments showed that Clostridium perfringens, a bacterium capable of producing large amounts of ammonia, multiplied in animals with MASH. Excess ammonia gradually damaged the gut's protective lining—much like cracks appearing in a protective wall—allowing harmful bacterial substances to leak into the bloodstream and reach the liver, where they triggered damaging immune reactions.

"We have clear proof that DT-109 helps protect the gut lining, which reduces the harmful substances from bacteria that can lead to MASH," said Eugene Chen, M.D., Ph.D., senior author of the study. "This compound shows benefits to the gastrointestinal system and has great potential as a treatment for MASH."

By reducing Clostridium perfringens and lowering ammonia production, DT-109 restored the gut barrier and eased liver inflammation. "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 co-author Jifeng. Zhang, Ph.D.

Researchers also observed signs that the compound may help prevent artery damage and could eventually prove useful in inflammatory bowel disease, although those possibilities remain under investigation.

Independent liver specialist Elliot Tapper, M.D., who was involved in the research, said, "What patients with MASH need is a safe and effective therapy capable of improving their liver and heart health. Of course, we are excited about these developments."

The researchers caution that the work remains preclinical. Human clinical trials are still needed to establish whether DT-109 is safe and effective in patients. The study also disclosed that the University of Michigan has patented DT-109 and licensed it to Diapin Therapeutics and that some investigators are inventors and hold financial interests related to the compound.