Scientists have uncovered a novel way to trap a harmful gut molecule before it can wreak havoc on blood sugar levels and liver health. 

A research team from McMaster University, Université Laval, and the University of Ottawa in Canada found that a byproduct from gut bacteria called D-lactate can enter the bloodstream. This causes the liver to produce excess fat and glucose, leading to a build-up of fat in both the bloodstream and liver.

Imbalances in gut bacteria are associated with serious chronic diseases. Approximately 38 million Americans have type 2 diabetes, and about 83 million are affected by fatty liver disease.

In a healthy digestive system, small levels of D-lactate are not problematic. However, diets rich in processed foods, sugars, and fats can encourage the growth of bacteria that produce this byproduct.

D-lactate reaches the liver, causing it to excessively produce glucose and fat and trigger inflammation. This strain on the liver can lead to steatosis, an initial stage of liver disease that might eventually lead to scarring.

To counter this, the researchers developed a biodegradable polymer ‘trap’ that captures D-lactate in the intestines. 

Experiments with obese mice fed a diet containing the polymer showed improved blood sugar control, insulin sensitivity, and liver health, all achieved without altering their diet or body weight.

The results suggest this approach could be used as a standalone or complementary treatment for metabolic disorders, providing a potential breakthrough in combating type 2 diabetes and fatty liver disease.

Approximately 38 million Americans have type 2 diabetes. The latest research points to a potential new treatment that could intercept the disease in the gut by targeting a harmful molecule produced by the body’s own gut bacteria

Obese mice, as well as people with obesity, naturally have higher levels of the lesser-known D-lactate in their blood, according to the researchers.

They discovered that the gut microbiome was the source. Most of the D-lactate comes from gut microbes and was shown to raise blood sugar and liver fat more aggressively, unlike the more familiar L-lactate made by muscles.

Dr Jonathan Schertzer, senior and corresponding author and professor in the Department of Biochemistry and Biomedical Sciences at McMaster University, said: ‘This is a new twist on a classic metabolic pathway.

‘We’ve known for nearly a century that muscles and the liver exchange lactate and glucose – a process called the Cori cycle. What we’ve discovered is a new branch of that cycle, where gut bacteria are also part of the conversation.’

To test its effects, they gave mice a potent oral dose of D-lactate. 

Their livers went into overdrive, producing more blood sugar and fat than ever before, confirming to scientists that D-lactate was not a harmless marker, but rather a powerful compound fuel that drives disease.

They aimed to create a safe polymer that would not be absorbed into the blood.

Their polymer trap was a compound mixed in with the food given to the mice. When the mice ate the mixture, the polymer compound traveled to their intestines undigested.

The above graph shows estimates for global diabetes cases. It is predicted that the number of people with the condition will more than double by the year 2050 compared to 2021

As gut bacteria produced D-lactate, the polymer acted like a magnet, binding to the D-lactate molecules and forming a stable complex, which was too large to be absorbed through the gut wall into the bloodstream. 

Essentially, the D-lactate was trapped in a form that the body could not take in.

Instead of being absorbed, the entire complex continued moving through the digestive system and was excreted in the feces.

Mice eating the polymer-enriched diet had significantly higher levels of D-lactate in their feces, proving to researchers that the polymer was binding to D-lactate in the gut and preventing its absorption, forcing it to be excreted.

They also had lower levels of D-lactate in their blood.

There were no changes in L-lactate absorption levels, though. Researchers did not find any changes to levels in the mice’s blood or fecal matter.

Their research offers a promising pathway to treat obesity-related conditions like type 2 diabetes and metabolic dysfunction-associated fatty liver disease (MASLD) at its source, the gut-liver axis.

Their approach, using a safe, biodegradable polymer compound, could lead to novel therapies that lower blood sugar, reduce liver fat, and combat inflammation without requiring changes in diet or body weight, representing a major shift from managing symptoms to intercepting the root cause of metabolic disorders.

The obesity rate among American adults increased from 21.2 percent in 1990 to 43.8 percent in 2022 for women and 16.9 percent to 41.6 percent for men

Their research was published in the journal Cell Metabolism.

Dr Jonathan Schertzer, a co-author and a member of the Centre for Metabolism, Obesity, and Diabetes Research (MODR) at McMaster, said: ‘This is a completely new way to think about treating metabolic diseases like type 2 diabetes and fatty liver disease.

‘Instead of targeting hormones or the liver directly, we’re intercepting a microbial fuel source before it can do harm.’