The gut is home to trillions of microbes, which can have a wide range of impacts on human health in various ways. These microbes produce bioactive molecules and modify chemicals that can have an effect on the human body, and scientists are beginning to reveal the specific ways that certain microbes can influence our health. Research has now suggested that blood sugar levels can be better controlled and damage to the liver can be reduced if the gut microbiome's output of a certain biochemical is limited. The findings have been reported in Cell Metabolism. This work may help pave the way toward using the gut microbiome to treat some metabolic disorders , such as type 2 diabetes or fatty liver disease, for example.
Gut bacteria are known to influence blood sugar levels, by affecting how much sugar is stored in the liver. These microbes are also known to influence disorders such as type 2 diabetes and a liver disease known as metabolic dysfunction-associated steatohepatitis (MASH). Individuals with diabetes and diabetes research models are known to carry unusually high levels of D-lactate in their blood and urine. When the researchers considered all of these points, they wanted to know more about the biological effect of D-lactate that comes from gut microbes.
In the Cori cycle, lactate produce by muscles is used by the liver to generate glucose, which, in turn, fuels muscle. In this process, muscles use L-lactate, while the liver utilizes blood glucose. But gut microbes make D-lactate, which can increase blood sugar and liver fat more dramatically than L-lactate.
This study showed that D-lactate from gut microbes ends up in the bloodstream, which causes the liver to generate excess amounts of sugar (in the form of glucose) and fat.
The team decided to sequester this D-lactate, using a biodegradable polymer in a mouse model. The polymer can attach to D-lactate to prevent its absorption by the body. When obese mice were treated with this D-lactate-trapping polymer, there were significant improvements in their health; insulin resistance was lowered and blood sugar levels were controlled more efficiently, and fatty liver disease symptoms like inflammation were reduced. This all happened without changing their diet.
"This is a new twist on a classic metabolic pathway," said senior study author Jonathan Schertzer, a professor at McMaster University, among other appointments. "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."
"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," Schertzer added.
Sources: McMaster University, Cell Metabolism