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 team from McMaster University, Université Laval and the University of Ottawa in Canada discovered that a byproduct created by gut bacteria, called D-lactate, can enter the bloodstream and prompt the liver to produce more fat and glucose than necessary. This leads to a build-up of fat in the bloodstream and liver.
Such imbalances in the gut microbiome are linked to serious chronic conditions. Type 2 diabetes and fatty liver disease affect roughly 38 million and 83 million Americans, respectively.
In a healthy gut, small amounts of D-lactate are not harmful. However, diets high in processed foods, sugars, and fats can promote overgrowth of bacteria that produce the molecule.
D-lactate travels to the liver, forcing it to overproduce glucose and fat while sparking inflammation. This stress on the liver can cause steatosis, an early stage of liver disease that may lead to scarring over time.
To counter this, the researchers developed a biodegradable polymer ‘trap’ that captures D-lactate in the intestines.
In experiments with obese mice fed a diet containing the polymer, the trap improved blood sugar control, insulin response, and liver health, all without changing diet or body weight.
The findings suggested the approach could serve as a stand-alone or complementary therapy for metabolic diseases, offering a potential breakthrough in the fight against 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.’
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