An experimental drug has reversed severe fatty liver disease in animal studies by repairing the gut and blocking harmful toxins from reaching the liver, researchers at Michigan Medicine reported. The compound, known as DT-109, cleared metabolic dysfunction-associated steatohepatitis, an advanced and increasingly common form of liver disease, in the study published in The Journal of Clinical Investigation.
The condition, often abbreviated as MASH, represents a serious stage of fatty liver disease in which fat accumulation is accompanied by inflammation and scarring. It has become a growing global health concern, closely linked to obesity and metabolic disorders, yet effective treatments have remained scarce, leaving many patients at risk of progressing to cirrhosis or liver failure.
The research team, led by Eugene Chen of the University of Michigan Medical School, focused on the connection between the gut and the liver. They found that a key driver of the disease is the proliferation of the bacterium Clostridium perfringens, which produces ammonia in the gut. Elevated ammonia levels erode the inner lining of the digestive tract and weaken the intestinal barrier, allowing toxins to pass through and reach the liver, where they trigger damaging inflammatory responses.
DT-109, a compound built from the amino acid glycine as a small three-part peptide, interrupted this process. In tests on mice and on nonhuman primates, it reduced the presence of Clostridium perfringens and lowered ammonia production in the gut, strengthening the intestinal barrier and restoring the integrity of both the gut and the liver. By targeting the underlying gut-liver pathway rather than the liver alone, the drug addressed a root cause of the disease.
The approach is notable because it reframes severe fatty liver disease as a disorder driven in part by the gut, opening a different avenue for treatment. Confirming the effect in nonhuman primates, whose biology more closely resembles that of humans, strengthens the case that the mechanism could translate to people, according to the researchers.
Despite the promising results, the findings come from animal models and will require clinical trials in humans before any therapy could become available. Still, the work points to a potential new strategy for a disease that currently offers patients limited options, and it underscores the growing recognition that the health of the gut can shape conditions well beyond the digestive system.
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