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Gut Microbes and Diet Interact to Affect Obesity

Gut microbes from lean people helped prevent mice from becoming obese—but only if the animals ate a healthy diet. This research could point the way to new treatments for obesity.

The human gut harbors a complex community of microbes that affect many aspects of our health. Evidence, mostly from studies of rodents, suggests that the gut microbiota may play a role in the development of obesity.

In earlier research, a team led by Dr. Jeffrey Gordon at the Washington University School of Medicine showed that obese and lean human twins have clear differences in their gut microbial communities. Most notably, the communities from obese twins have less diverse bacterial species. In their new study, the scientists used a mouse model to further explore the role that gut microbes play in obesity and metabolism. Their work was funded in part by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Institute on Aging (NIA).

The team took gut microbes from 4 sets of human twins in which one was lean and the other obese. They introduced the microbes of each twin into different groups of mice that had been raised in a previously germ-free environment. They then observed weight and metabolic changes in the mouse groups when fed the same diet. The results were published in Science on September 6, 2013.

Mice populated with microbes from a lean twin stayed slim, whereas those given microbes from an obese twin quickly gained weight. The “lean” and “obese” microbes had different measurable effects on the body’s metabolism.

When mice are housed in the same cage, microbiota transfer between cage-mates is common. The researchers thus placed together mice harboring microbes from lean twins and mice carrying microbes from obese twins.

The scientists found that specific groups of microbes transferred from lean mice to their obese cage-mates, who began with less diverse microbial communities. The transfer only occurred in one direction: from lean to obese mice. This transfer appeared to prevent obesity and encourage metabolic profiles resembling those of lean mice.

The researchers were curious about the impact that a typical American diet, high in saturated fats and low in fiber, would have on these obesity-fighting microbes. The mice had initially been given a chow that was low in saturated fat and high in fruits and vegetables. The scientists repeated the experiment, but this time fed the mice a diet high in saturated fats and low in fruits and vegetables.

On the high-fat diet, the lean mice’s bacteria weren’t able to colonize the obese mice, and the mice developed obesity. These results show that expanding gut microbe diversity can help improve health. However, it takes more than microbes working alone; the success of the approach depends on diet.

“These experiments show that eating a healthy diet encourages microbes associated with leanness to become incorporated into the gut,” Gordon says. “But a diet high in saturated fat and low in fruits and vegetables thwarts the invasion of microbes associated with leanness. This is important as we look to develop next-generation probiotic cocktails composed of defined collections of naturally occurring human gut microbes as a treatment for obesity.”

— by Katherine Wendelsdorf, Ph.D.