Scientists have uncovered a connection between the immune system, obesity, and gut bacteria. Healthy mice carry beneficial Clostridia bacteria, a class consisting of around 25 strains, in their guts as part of the normal mouse microbiome. In mice with an impaired immune system, however, there was a gradual loss of Clostridia as they got older, as they also became obese. The mice remained obese even when fed different diets, but once they were exposed to Clostridia again, they lost the weight. There are also previous findings in humans that suggest this work may be true for people as well. The new work has been reported in Science.
"Now that we've found the minimal bacteria responsible for this slimming effect, we have the potential to really understand what the organisms are doing and whether they have therapeutic value," said the co-senior author of the report June Round, Ph.D., an associate professor of pathology at University of Utah Health.
The investigators learned that Clostridia prevents the intestine from absorbing fat, stopping weight gain. So-called germ-free mice that have no microbiome had more fat on their bodies than mice carrying only Clostridia. In these Clostridia-carrying mice, a gene called CD36 that controls the uptake of fatty acids was expressed at lower levels.
Researcher Charisse Petersen, Ph.D. observed that genetically engineered mice that lacked a gene called myd88 were incredibly obese. The gene is connected to the immune system. Petersen knew that the immune system has to maintain balance in the gut microbiome. Imbalances in the microbiome can allow certain species to dominate, or damaging bacteria to become too influential, which can both be deleterious to health.
It turned out that the immune system in the genetically engineered mice was unable to respond correctly to bacteria. Their immune system made fewer antibodies that interact with the microbiome, making it challenging for Clostridia to reside there. More fat was absorbed in these mice, which eventually gained weight and began to develop type 2 diabetes symptoms.
People that are obese have also been found to lack Clostridia, noted Round. Obese individuals may also have an impaired immune response.
"We've stumbled onto a relatively unexplored aspect of type 2 diabetes and obesity," said Round. "This work will open new investigations on how the immune response regulates the microbiome and metabolic disease."
This research may help create new therapeutics for obesity that involve restoring a healthy microbiome. A probiotic approach may not work for everyone, of course, because of many factors influencing it including diet and genetics. Researchers may also be able to figure out which bacterial molecules stop the body from absorbing fat; these compounds represent another type of treatment strategy.
"These bacteria have evolved to live with us and benefit us," Petersen added. "We have a lot to learn from them."