A team of Canadian scientists has found that trapping a little-known fuel made by gut bacteria could help control blood sugar and protect the liver. The discovery points to a surprising link between the microbiome and serious metabolic diseases, including type 2 diabetes and fatty liver disease.

The research, led by McMaster University in collaboration with Université Laval and the University of Ottawa, shows how a molecule from gut microbes can enter the bloodstream, pushing the liver to produce excess glucose and fat. Here, we’ll look at how this fuel source works, what happens when it is blocked, and why the findings could shape future treatments for chronic conditions.

How blocking this gut fuel works

The study, published in Cell Metabolism, builds on decades of research into the Cori cycle, a process discovered by Nobel Prize winners Carl and Gerty Cori that explains how muscles and the liver exchange fuel. Traditionally, this cycle focuses on L-lactate, produced by muscles, which the liver converts to glucose for energy.

The Canadian team uncovered another branch of this pathway involving D-lactate, a similar molecule but mostly produced by gut bacteria. In people with obesity, D-lactate levels were found to be unusually high. Unlike muscle-produced L-lactate, this gut-derived version appears to spike blood sugar and increase liver fat more aggressively.

To counter this, researchers developed what they call a “gut substrate trap”, a biodegradable polymer designed to bind to D-lactate in the intestines. Once bound, the molecule cannot enter the bloodstream. In mouse experiments, this led to lower blood glucose, reduced insulin resistance, and less liver inflammation and scarring, all without changes in diet or weight.

Jonathan Schertzer, senior author and professor in the Department of Biochemistry and Biomedical Sciences at McMaster, explained: “Instead of targeting hormones or the liver directly, we’re intercepting a microbial fuel source before it can do harm“.

How does this research impact future treatments

This discovery adds to growing evidence that the microbiome plays a major role in metabolic diseases. If further research confirms the same results in humans, blocking D-lactate could become a new strategy for managing conditions that currently rely on controlling hormones, diet, or weight loss. Potential implications of the study include:

Type 2 diabetes management: Reducing D-lactate may improve blood sugar control without additional medication.
Nonalcoholic fatty liver disease (NAFLD): Trapping this molecule could slow or reverse liver fat buildup and inflammation.
Obesity-related complications: Even without weight loss, targeting gut-derived fuels could lower risks linked to high blood sugar and liver damage.
Microbiome-based therapies: Opens the door to treatments that focus on gut bacterial activity rather than systemic interventions.
Preventive health strategies: Screening for D-lactate levels might help identify at-risk individuals earlier.

The findings also show how the gut and liver communicate in ways scientists are only beginning to understand. By intercepting harmful byproducts before they circulate through the body, therapies could target the source of the problem instead of treating the symptoms.

While the current results come from animal models, the researchers believe similar methods could be adapted for human trials. If successful, this approach may offer a non-invasive and safe option for millions of people living with metabolic diseases.