Scientists have long suspected that the trillions of microbes living in our gut do more than help digest food. Now, new research suggests they may play a direct role in shaping how our bodies handle sugar and fat — key factors in obesity and type 2 diabetes.
A recent study conducted at Harvard University, with support from Brazil’s São Paulo Research Foundation (FAPESP), has uncovered a network of small molecules produced by gut microbes that travel from the intestine to the liver and then throughout the body. These compounds, known as metabolites, appear to influence how the liver processes energy and how sensitive the body is to insulin. The findings were published in the journal Cell Metabolism and could open the door to new ways of treating metabolic disease.
The gut–liver highway
To understand the discovery, it helps to know how blood flows through the body. Much of the blood leaving the intestine doesn’t go straight into the general circulation. Instead, it travels through a special vessel called the hepatic portal vein, which delivers nutrients and microbial byproducts directly to the liver first.
“The liver is essentially the first organ to see what’s coming from the gut,” explains lead author Vitor Rosetto Muñoz, a postdoctoral researcher at the University of São Paulo who conducted part of the study at Harvard’s Joslin Diabetes Center. Once these gut-derived compounds reach the liver, they can be modified, broken down, or released into the bloodstream to affect other organs.
By comparing blood from the hepatic portal vein with blood circulating throughout the rest of the body, the researchers were able to pinpoint which metabolites come from the gut and how they may influence metabolism along the way.
Why the gut microbiome matters
In recent years, researchers have learned that people with obesity, insulin resistance, or type 2 diabetes often have a different mix of gut bacteria than people without these conditions. What’s been harder to determine is exactly how those microbes affect metabolism.
To explore this, the team studied mice with different genetic risks for obesity and diabetes. They analyzed metabolites in both portal vein blood and peripheral blood, offering a clearer picture of what the liver is exposed to right after digestion.
In healthy mice, researchers identified more than 100 metabolites enriched in blood traveling from the gut to the liver. But in mice genetically prone to obesity and diabetes (and fed a high-fat diet), that number dropped dramatically. This suggests that diet and genetics together can reshape the chemical messages sent from the gut to the liver.
Interestingly, mice that were naturally resistant to metabolic disease showed a different metabolite pattern altogether. This points to a complex interaction between a person’s genes, their environment, and their gut microbiome.
Disrupting the microbiome changes metabolism
To test whether gut bacteria were truly responsible for these changes, researchers treated some mice with antibiotics that altered their gut microbiome. As expected, this disrupted microbial populations and also shifted the types of metabolites found in the blood.
One metabolite that increased stood out: mesaconate, a compound involved in the Krebs cycle, which is the process cells use to generate energy. When scientists exposed liver cells to mesaconate and related molecules in the lab, they saw improvements in insulin signaling. The compounds also helped regulate genes linked to fat buildup and fat burning in the liver — two processes that are often impaired in metabolic disease.
These findings suggest that certain gut-derived metabolites can directly improve liver metabolism, even in the context of a high-fat diet.
What this could mean for the future
While this research was done in mice, it provides a detailed map of how gut microbes may influence metabolic health through the liver. The next step is to better understand how each metabolite is produced and how it behaves in the body.
Over time, this work could help scientists identify specific microbial byproducts that might be used as treatments—or inspire therapies that reshape the gut microbiome to improve insulin sensitivity and reduce the risk of obesity and type 2 diabetes.
So, remember: What happens in your gut doesn’t stay in your gut. It may travel straight to your liver and shape your metabolic health in powerful ways!
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Source: “Harvard gut discovery could change how we treat obesity and diabetes,” ScienceDaily, 12/14/25
Source: “Metabolites produced in the intestine play a central role in controlling obesity and diabetes,” Agencia.fapesp.br, 11/26/25
Source: “Portal vein-enriched metabolites as intermediate regulators of the gut microbiome in insulin resistance,” ScienceDirect, 10/7/25
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