What if a molecule made by a bacterium in the gut could help the body burn more of the fat most closely linked to metabolic disease?
New research from Duke University School of Medicine points to a surprising possibility: a naturally occurring human gut bacterium produces a sugar molecule that helps obese mice increase energy expenditure and reduce visceral fat that accumulates around internal organs and is associated with diabetes and heart disease.
Potential new strategy to target obesity
The findings, published Sept. 23 in Cell Host & Microbe, identify a previously unknown way the microbiome can influence metabolism and suggest a potential new strategy for targeting obesity.
Researchers led by Neeraj Surana, MD, PhD, assistant professor in the departments of Pediatrics and Molecular Genetics and Microbiology, discovered the bacterium Clostridium immunis, a newly identified member of the healthy human gut microbiome.
The bacterium produces a complex sugar called an exopolysaccharide, modified with a molecule called phosphocholine. Using genetically modified versions of C. immunis, researchers found that phosphocholine was essential for protecting against metabolic disease.
Burning fat faster
In obese mice, the bacterial molecule reduced visceral fat and increased metabolic activity, particularly in visceral adipose tissue. Importantly, the mice did not eat less or lose muscle mass.
That distinguishes the approach from medications, like GLP-1s, that promote weight loss primarily by reducing food intake. Instead, the bacterial molecule increases how much energy the animals expend, helping them burn fat faster.
The team also uncovered an immune pathway involved in the effect. The bacterial molecule reduced levels of the immune signaling protein IL-22 in the small intestine and visceral fat, leading to increased metabolic activity in visceral adipose tissue.
The discovery may have relevance beyond mice. When researchers analyzed microbiome data from thousands of people, they found that genes involved in producing phosphocholine were less abundant in people with obesity or high triglyceride levels.
"GLP-1 drugs have transformed treatment of obesity and its associated comorbidities, but they do not work for everyone and often cause significant side effects,” Surana said. “Our bacterium and its sugar molecule could be used as either an adjunct or alternative to GLP-1 medications. Given that the metabolic rate generally decreases in middle age, our findings suggest this could be an intervention that leads to overall healthier aging as well.”
The findings do not yet show that the bacterium or its molecule can treat obesity in people. Researchers are seeking funding for clinical studies to determine whether the approach can reduce visceral fat and improve metabolic health in humans.
The study was supported by the National Institutes of Health, The Hartwell Foundation, the Duke Microbiome Center, Duke’s Gilhuly Accelerator Fund, the American Heart Association, and the National University of Singapore.