Gut-Derived Metabolites Unlock New Treatments for Diabetes and Obesity

The ongoing battle against chronic diseases like obesity and Type 2 diabetes—which affects an estimated 589 million adults worldwide as of 2025—may soon be fought on a new front: the chemistry flowing between the gut and the liver. A new Harvard study has identified the liver as a central “hub” that processes metabolites produced by gut microbes before distributing them throughout the body, significantly influencing our metabolism.

This groundbreaking research, supported by FAPESP, suggests that future therapies may involve targeting gut-derived chemistry to reset how the body handles fat and glucose, moving beyond traditional methods like controlling appetite or managing blood sugar.

The research team focused on specific metabolic compounds traveling from the intestine to the liver via the hepatic portal vein. By examining mice with different genetic susceptibilities to metabolic diseases, the scientists compared those who remained healthy against those who developed problems when fed a high-fat diet.

The results revealed a crucial regulatory link: In metabolically healthy mice, the portal vein contained over 110 distinct gut-derived metabolites, but in susceptible mice on a high-fat diet, this number sharply dropped to 48. This demonstrates that both heredity and diet interact complexly with the gut microbiome to define the mix of microbial products sent to the liver, impacting metabolic health.

The study went further than past research, which primarily correlated microbial composition with disease risk. This new work identified specific metabolites, tracking their flow from the intestine to the liver and bloodstream.

When researchers applied one of these metabolites, mesaconate (linked to the Krebs cycle), to liver cells in lab tests, it proved highly beneficial. This treatment improved insulin signaling and helped regulate essential functions like fat accumulation and fat-burning in the liver.

This discovery points to a direct mechanism by which the gut microbiome controls fat storage and glucose handling. Where management of Type 2 diabetes and obesity has traditionally focused on lifestyle, blood-sugar control drugs, or surgery, this research suggests the possibility of developing new drugs or dietary strategies that reprogram the metabolism at a deeper, molecular level by mimicking or encouraging these protective microbial products. The ultimate goal is to better characterize these key metabolites to inform the discovery of molecules capable of treating metabolic diseases in the future.

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🔖 Sources

Harvard Study Unlocks New Potential Treatments for Diabetes and Obesity

Diabetes management: Harvard study finds new potential treatments for obesity

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Keywords: Gut-derived metabolites

Gut-derived metabolites

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