Gut Bacteria May Influence Metabolic Syndrome

Research Matters
March 15, 2010
Gut Bacteria May Influence Metabolic Syndrome

A new study in mice supports recent findings that gut microbes may contribute to metabolic syndrome. It also suggests that part of the immune system plays a role in the development of metabolic syndrome.


Common gut bacteria. Image by David Gregory and Debbie Marshall, all rights reserved by Wellcome Images.Metabolic syndrome is a cluster of conditions that increases the risk for heart disease and stroke. Doctors consider someone to have metabolic syndrome when they have 3 or more of these risk factors: abdominal obesity, elevated blood pressure, high triglyceride levels, low HDL (good cholesterol) levels and diabetes or pre-diabetes.

Recent human studies suggest that gut microbial communities may contribute to obesity and related health conditions. Microbes might influence obesity by affecting your ability to extract energy from food. In laboratory experiments, transferring bacteria from certain obese mice to wild-type animals leads to increased fat in the recipient mice. But how do different microbes wind up in different guts in the first place? A research team led by Drs. Matam Vijay-Kumar and Andrew T. Gewirtz at Emory University set out to investigate. They were supported by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the Crohn's and Colitis Foundation of America.

The scientists did earlier work with a protein called toll-like receptor (TLR) 5 that is highly expressed in the lining of the intestine. TLR5 plays an important role in recognizing microbes, activating a branch of the immune system called the innate immune system. Mice lacking TLR5 developed colitis and gained more weight than equivalent mice without the gene deletion. In that study, however, the scientists didn’t ensure that all the mice began with equivalent gut microbes. For the new study, the researchers made sure to standardize gut microbes from the beginning by starting with the same mouse line from the same supplier for all their experimental and control mice.

In the advanced online edition of Science on March 4, 2010, they reported that mice lacking TLR5 grew about 20% heavier than control mice by 20 weeks of age. The mice ate about 10% more food and made more body fat than control mice. They also developed several features of metabolic syndrome, including higher triglyceride levels and cholesterol, an increase in blood pressure and insulin resistance—a characteristic of type 2 diabetes.

All the mice gained weight when they were fed a high-fat diet for 8 weeks, but the TLR5-deficient mice also became diabetic and developed fatty livers. When the scientists gave TLR5-deficient mice the same amount of food eaten by control mice, the mice didn't become obese, yet they were still insulin resistant.

The scientists analyzed bacteria from the mouse guts and found differences in 116 types of bacteria between the TLR5-deficient mice and control mice. To test whether these microbes can influence overeating and metabolic syndrome, they transplanted gut microbes from TLR5-deficient mice into germ-free control mice. Similar to TLR5-deficient mice, the recipient mice overate, became obese and diabetic.

"It has been assumed that the obesity epidemic in the developed world is driven by an increasingly sedentary lifestyle and the abundance of low-cost high-calorie foods," Gewirtz says. "However, our results suggest that excess caloric consumption is not only a result of undisciplined eating but that intestinal bacteria contribute to changes in appetite and metabolism." The next step will be to see whether gut microbes can affect people's eating behavior and the development of metabolic syndrome, as it does in mice.

—by Harrison Wein, Ph.D.

Related Links:
What Is Metabolic Syndrome?:
http://www.nhlbi.nih.gov/health/dci/Diseases/ms/ms_whatis.html

Gut Microbiomes Differ Between Obese and Lean People:
http://www.nih.gov/researchmatters/december2008/12082008gutmicrobiomes.htm