March 15, 2010

Intestinal bacteria may be culprit in obesity

Increased appetite and insulin resistance can be transferred from one mouse to another via intestinal bacteria, according to research published online March 4 by Science magazine.

The results, from a team led by Emory pathologist Andrew Gewirtz, strengthens the case that intestinal bacteria can contribute to human obesity and metabolic disease.

“It has been assumed that the obesity epidemic in the developed world is mainly driven by an increasingly sedentary lifestyle and the abundance of low-cost high-calorie foods,” Gewirtz says. “Previous research has suggested that intestinal bacteria can influence how well energy is absorbed from food, but these findings demonstrate that they can actually influence appetite and metabolism.”

Gewirtz, Matam Vijay-Kumar and colleagues have been studying a mouse strain with an altered immune system. The mice were engineered to lack a gene, Toll-like receptor 5 (TLR5), which helps cells sense the presence of bacteria.

TLR5-deficient mice are about 20 percent heavier than regular mice and have elevated triglycerides, cholesterol and blood pressure. They tend to consume about 10 percent more food than their regular relatives, and have elevated blood sugar and increased production of insulin. In short, TLR5-deficient mice have “metabolic syndrome,” a cluster of disorders that in humans can lead to heart disease and diabetes.

In collaboration with Ruth Ley at Cornell University, Gewirtz’s team found that TLR5-deficient mice had an altered set of the bacterial species in their intestines. Ley’s research has previously shown that intestinal bacterial populations differ between obese and lean humans.

Under certain conditions, many TLR5-deficient mice develop inflammatory bowel disease, while the majority of the mice have chronic low-level inflammation, which may dampen their bodies’ response to insulin.

Treating TLR5-deficient mice with strong antibiotics, enough to kill most of the bacteria in the intestine, reduces their metabolic abnormalities. In addition, transfer of intestinal bacteria from TLR5-deficient mice to regular mice, after they were first treated with antibiotics, conferred many of the characteristics of metabolic syndrome including increased appetite, obesity, elevated blood sugar and insulin resistance.

Gewirtz’s team plans additional research on humans’ intestinal bacterial populations, which are thought to be relatively stable after acquisition at birth from family members.

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