Scientists discover a surprising new way of fighting diabetes

Intestinal microbes produce d-lactate which worsens metabolism. A trap for it restores healthier blood sugar and liver function.

A group of Canadian researchers has identified an unexpected way of reducing blood sugar and protecting the liver: by capturing a little -known fuel produced by intestinal bacteria before entering the body and causing damage.

The results, published in Cellular metabolismcould open the door to new therapies to treat metabolic diseases such as type 2 diabetes and fatty liver disease.

The microbial molecule disrupts metabolism

Scientists from McMaster University, Laval University and the University of Ottawa have discovered that a molecule generated by intestinal microbes can cross blood circulation, where it leads to the liver to overcome glucose and fat. By conceiving a method to trap this molecule in the intestine before reaching traffic, they have reached striking improvements in the regulation of blood sugar and fatty liver disease in obese mice.

“This is a new turn on a classic metabolic path,” explains Jonathan Schertzer, author and superior professor and corresponding to the department of biochemistry and biomedical sciences of McMaster. “We have known for almost a century that the muscles and the liver have exchanged lactate and glucose – a process called Cori Cycle. What we have discovered is a new branch of this cycle, where intestinal bacteria are also part of the conversation. ”

In 1947, Carl Ferdinand Cori and Gerty Theresa Cori received the Nobel Prize for Physiology or Medicine for having shown how the lactate generated by the muscles fueled the liver to make blood sugar, which then dates back to the muscle activity of power. Their work has established the basics of understanding how the muscles use a form of lactate (L-LACTATE) and how the liver uses blood sugar in a closely coordinated fuel exchange.

The Canadian team has now shown that obese mice – and even humans with obesity – have high levels of a different, d -lactate molecule in their blood. Unlike well-studied L-Lactate produced by muscles, D-Lactate comes largely from intestinal bacteria and has been found to increase blood sugar and liver fats.

Block d-lactate with a substrate trap

To stop this, the researchers created a “intestinal substrate trap” – a safe and biodegradable polymer that binds to d -lactate in the intestine and prevents him from absorbing. The mice fed on this trap had lower blood sugar, less insulin Resistance and reduction of inflammation of the liver and fibrosis – all without changing their diet or their body weight.

“This is a whole new way of thinking of treating metabolic diseases such as type 2 diabetes and fatty liver disease. Instead of targeting hormones or the liver directly, we intercept a source of microbial fuel before we can do harm, “explains Schertzer, member of the Center for Metabolism, obesity and research institutes on the health of diabetes. Schertzer holds a Canada Research President in metabolic inflammation.

Reference: “The trans intestinal substrate of d-lactate from the microbiota improves blood sugar and fatty hepatic disease in obese mice” by Han Fang, Fernando F. Anhê, Dana Kukje Zada, Nicole G. Barra, Rodrigo Rodrigues e-Lieda, Branne T. Mcalpin, Ryan Wyliem, Étiane Auditne, Conor O’Dwyer, Peyman Ghorbani, Morgan D. Fullerton, Claudia Gagnon, André Tchernof, André Marette and Jonathan D. Scheritzer, July 29, 2025, Cellular metabolism.
Two: 10.1016 / J.CMET.2025.07.001

Funded by Canadian Health Research Institutes (IRSC).

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