Biodegradable gut 'trap' captures bacterial D‑lactate, improves blood sugar and liver health in mice

Scientists in Canada report a novel, intestine‑targeted approach that prevented a gut‑derived molecule from driving higher blood sugar and liver fat in obese mice, a finding that points to a potential new route for treating metabolic diseases.

Researchers from McMaster University, Université Laval and the University of Ottawa described a biodegradable polymer that binds and sequesters D‑lactate, a byproduct produced by certain gut bacteria. In the mouse experiments the compound reduced levels of D‑lactate in the blood, improved glucose control and insulin response, and lowered markers of liver fat and inflammation despite no changes in diet or body weight.

The team identified D‑lactate as a microbially produced molecule that can enter the bloodstream and prompt the liver to increase glucose production and convert more substrates into fat. That process can contribute to a buildup of fat in the liver known as steatosis and foster inflammatory changes associated with metabolic dysfunction. The researchers said obese mice — and people with obesity — tend to have higher circulating D‑lactate tied to changes in their gut microbiome.

"This is a new twist on a classic metabolic pathway," said Dr. Jonathan Schertzer, senior and corresponding author and a professor in McMaster's Department of Biochemistry and Biomedical Sciences. He described the finding as a previously unrecognized branch of the Cori cycle in which gut bacteria contribute a metabolic fuel that affects liver function.

In laboratory tests the investigators administered an oral dose of D‑lactate and observed that mice developed heightened hepatic glucose and fat production, confirming the compound's capacity to drive metabolic disturbance. To block that effect, they designed a polymer that passes through the digestive tract undigested and selectively binds D‑lactate as it is produced by gut microbes. The resulting polymer–D‑lactate complex is too large to cross the gut wall and is excreted in feces.

Mice that received food containing the polymer had higher D‑lactate concentrations in their feces and lower levels in their blood, evidence that the compound was capturing the molecule before it could be absorbed. Measurements of L‑lactate, the form of lactate produced by muscle, were unchanged.

The research, published in the journal Cell Metabolism, reported improvements in glycemic control and markers of liver health in obese mice fed the polymer‑enriched diet. The investigators emphasized that these benefits occurred without reductions in body weight or alterations in caloric intake.

Type 2 diabetes and fatty liver disease affect large numbers of Americans; researchers cited estimates of roughly 38 million people with type 2 diabetes and about 83 million with fatty liver disease. Diets high in processed foods, sugar and fat can promote overgrowth of bacteria that produce D‑lactate, the team said, linking contemporary dietary patterns to shifts in microbial metabolism that may contribute to chronic metabolic disease.

The authors framed the polymer approach as an interception of a microbial fuel source rather than a direct targeting of hormones or liver enzymes. The compound is described as biodegradable and designed not to be absorbed into the bloodstream.

The study is preclinical and limited to mouse models. The investigators noted that further research is required to determine safety, dosing and effectiveness in humans and to assess long‑term outcomes. The authors did not report clinical trial data and the timeline for human testing was not specified.

If future studies confirm similar effects in people, the approach could represent a shift in strategies to treat metabolic disorders by modifying interactions along the gut–liver axis rather than solely treating downstream consequences. The researchers said the polymer could potentially be used alone or alongside existing therapies to reduce blood sugar, liver fat and inflammation by preventing absorption of a harmful microbial metabolite.