A team of Canadian researchers has uncovered a novel strategy to improve blood sugar control and reduce liver damage—by trapping a hidden fuel source produced by gut bacteria before it enters the bloodstream. Their findings, published in Cell Metabolism, offer a promising new approach to treating metabolic diseases such as type 2 diabetes and fatty liver disease.
A Microbial Twist on a Classic Metabolic Pathway
As reported by medicalxpress, the study, conducted by scientists from McMaster University, Université Laval, and the University of Ottawa, revealed that a molecule made by gut microbes can infiltrate the bloodstream and overstimulate the liver to produce excess glucose and fat. This overproduction worsens conditions like insulin resistance and fatty liver.
“This is a new twist on a classic metabolic pathway,” said Jonathan Schertzer, senior and corresponding author, and professor of biochemistry and biomedical sciences at McMaster.
“We’ve known for nearly a century about the Cori cycle between muscles and the liver. What we’ve found is a microbial branch of that cycle, involving the gut.”
D-Lactate: The Hidden Culprit
Traditionally, the Cori cycle explains how L-lactate, generated by muscles during activity, helps the liver produce glucose. But the Canadian team discovered that people with obesity—and obese mice—have elevated levels of D-lactate, a lesser-known molecule produced by gut bacteria, not muscles. Unlike L-lactate, D-lactate raises blood glucose and liver fat more aggressively.
Introducing the ‘Gut Substrate Trap’
To counter the harmful effects of D-lactate, the researchers developed a “gut substrate trap”—a biodegradable, safe polymer that binds specifically to D-lactate in the intestines. This prevents the molecule from entering the bloodstream and impacting the liver.
When obese mice were fed this polymer, the results were striking:
- Improved blood sugar levels
- Reduced insulin resistance
- Less liver inflammation and fibrosis
Importantly, these benefits were achieved without altering diet or body weight, demonstrating the powerful impact of gut-derived molecules on metabolic health.
A New Frontier in Treating Metabolic Diseases
“Instead of targeting hormones or the liver directly, we’re intercepting a microbial fuel source before it can cause harm,” explained Schertzer, who also holds a Canada Research Chair in Metabolic Inflammation and is a member of McMaster’s Center for Metabolism, Obesity, and Diabetes Research (MODR).
This research sheds light on the microbiome’s critical role in chronic diseases and opens the door to non-invasive, gut-targeted therapies for conditions that affect millions worldwide.
As our understanding of the gut-liver axis grows, targeting microbial metabolites like D-lactate could represent a major shift in how we manage obesity-related illnesses in the future.