Researchers at Duke University in the US have identified a native human gut bacterium that, by producing a complex sugar, can increase the body's energy expenditure and reduce visceral fat; a finding that, if confirmed in humans, could open a new path in treating obesity and metabolic disorders.
The study, published on September 23 in the journal Cell Host & Microbe, was led by Niraj Surana, assistant professor in the departments of pediatrics and molecular genetics and microbiology at Duke University. Surana had previously worked on this same bacterium in the context of inflammatory bowel diseases, and now with his team has discovered a new role for it in metabolism.
The microbe studied is a species called Clostridium immunis, which has recently been identified in the healthy human gut microbiome. Prior to this research, this bacterium was mostly known for its role in modulating immune responses and protecting against intestinal inflammation, but the new study shows its capabilities go beyond that domain.
The sugar that helped burn fat
This bacterium produces a compound called an exopolysaccharide that contains a molecule known as phosphocholine in its structure. To examine the exact role of this molecule, the researchers genetically manipulated samples of the bacterium to disable the biosynthetic pathway that makes phosphocholine. The result showed that without this specific molecule, the protective effect of the produced sugar against metabolic disorders disappears; a finding that highlights the importance of this small structural component in the overall function of the compound.
Testing the compound on obese mice showed their visceral fat-the fat that accumulates around internal organs and whose increase is associated with higher risk of type 2 diabetes and cardiovascular disease-decreased. At the same time, the mice's metabolism, especially in the same visceral fat tissue, increased.
Notably, during the experiment the mice did not eat less and no loss of lean mass was observed; what changed was solely their energy expenditure. This feature distinguishes the finding from the action of widely used weight‑loss drugs, namely the GLP‑1 class, which mainly help weight loss by reducing appetite and thereby food intake. In contrast, the compound discovered in this study increased the body's energy expenditure directly without reducing food intake.
The role of the immune system in the story
Another part of the research focused on the role of the immune system in this process. The researchers found that this sugar reduces levels of an immune signaling protein called interleukin‑22 in the small intestine and visceral fat tissue, and this reduction is associated with increased metabolism in visceral fat tissue. This finding suggests the connections among the gut microbiome, the immune system, and whole‑body metabolism are more complex than previously thought, and gut bacteria can influence fat storage and consumption in the body directly via immune pathways.
Beyond animal experiments, the research team also examined microbiome data from thousands of humans. This review showed that genes involved in making phosphocholine are found less than usual in people with obesity and in people with high blood triglyceride levels. However, the researchers emphasize this finding is merely a statistical correlation and alone cannot prove a causal relationship between lack of these genes and the development of obesity or elevated triglycerides; a question that requires further studies in humans.
Distance to a real treatment
Surana explained the potential place of this finding in future obesity treatment, saying GLP‑1 drugs have transformed obesity treatment and its related diseases in recent years, but these drugs are not effective for all patients and in some people come with significant side effects. He said the mentioned bacterium and its produced sugar might in the future be studied as an adjunct to these drugs or even a replacement. He also pointed to the natural decline in metabolic rate in middle age and believes that if this mechanism is confirmed in humans, its application could go beyond treating obesity and help preserve metabolic health at older ages.
However, the researchers clearly emphasize that there is a long way to go before reaching an effective treatment for humans. Most of the data obtained so far come from mouse experiments, and human analyses currently only show a correlation between this biosynthetic pathway and metabolic status, not a proven relationship. The research team is now working to secure funding to begin clinical studies in humans; studies that will determine whether this mechanism can also reduce visceral fat and improve metabolism in humans.
This study, published in Cell Host & Microbe, was funded by the National Institutes of Health, the Hartwell Foundation, the Duke Microbiome Center, the Duke Guloly Accelerator Fund, the American Heart Association, and the National University of Singapore.