By Ayala Sahel, Staff Writer
The liver plays a vital role in the human body, aiding in metabolism, digestion, nutrient storage, protein production, and detoxification. It plays a roleplays a role in regulating blood sugar by storing glycogen, stores essential vitamins and minerals, and produces bile, which helps digest fat. It builds proteins needed for blood clotting and converts harmful ammonia into urea, safely removing it from the body. Because the liver plays such a major role in our functioning, damage to it can have widespread consequences throughout the body.
Around 7% of people worldwide suffer from Metabolic Dysfunction-Associated Steatohepatitis (MASH), a severe form of fatty liver disease that is characterized by an accumulation of fat in the liver, inflammation, and damage to liver cells. Over time, persistent inflammation causes the liver to produce scar tissue in a process called fibrosis. As scar tissue continues to accumulate, the condition can develop into cirrhosis, permanently impairing liver function. Cirrhosis can then lead to many complications such as fluid buildup in the stomach, swollen veins in the esophagus, an enlarged spleen, liver cancer, and eventually end-stage liver failure.
In its early stages, MASH can often be managed by lifestyle changes such as weight loss, exercise, and an improved diet. Most recently, the FDA approved Resmetirom, a drug that has been shown to reduce liver fat and, in some patients, even slow or reverse liver scarring. While this is a major step forward in MASH treatment, Resmetirom primarily deals with the damage occurring in the liver itself.
Researchers have increasingly recognized that the liver does not work alone. Through what is known as the gut-liver axis, the gut and liver are in constant communication. When the intestinal barrier becomes damaged, harmful bacteria and bacterial products can enter the bloodstream, traveling to the liver and making the inflammation worse. Because Resmetirom does not address the damage to the gut, researchers have begun working on a treatment that would target both organs simultaneously.
Scientists at the University of Michigan have developed a drug named DT-109, which was found to be effective in treating both the liver and the gut in animal models. Researchers discovered that a gut bacterium named Clostridium perfringens results in high production of ammonia in the gut. The excess amount of ammonia causes damage to the intestinal lining, weakening the gut’s protective barrier and allowing harmful bacteria to enter the bloodstream. Once these substances enter the bloodstream, they reach the liver, worsening inflammation and accelerating the damage caused by MASH.
DT-109 was tested in both mice and nonhuman primates. In both animal models, the drug consistently reduced the level of Clostridium perfringens, lowering ammonia levels, restoring the intestinal barrier, and preventing harmful bacteria from entering the bloodstream. As a result, inflammation of the liver was reduced, and signs of MASH in both organs improved.
These findings are very promising, as nonhuman primates share many physiological similarities with humans, making them an important step before starting clinical trials on people. Although much more research is needed before DT-109 can be used on patients, the study highlights it as a new approach to treating MASH. Rather than focusing solely on liver damage, DT-109 addresses one of the underlying factors of the disease by treating the gut. Furthermore, researchers observed that the drug prevented vascular calcification in animal models, suggesting DT-109 may have uses beyond MASH in treating cardiovascular diseases.
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