A Hidden Trigger of Obesity: Intestinal Bugs

If you're fighting the battle of the bulge, most of your attention — and frustration — is probably aimed at your midsection. It makes sense, since that's where the extra pounds tend to gravitate, especially with the creep of middle age, piling on to form that dreaded spare tire.

But a growing body of research suggests there's another, less visible reason to focus on your gut if you want to lose weight. Scientists led by Andrew Gewirtz at Emory University reveal that your intestines harbor a universe of bacteria — the so-called gut microbiota — that may play an important role in whether your body will store the food you eat as extra pounds.

Gewirtz's team, including researchers at Emory, Cornell University and the University of Colorado at Boulder, became intrigued by the relationship between gut bugs and weight when they noticed that lab mice lacking a certain protein had more of the bugs than other animals and were about 15% heavier. These mice also had a higher level of inflammation, which the authors explain in their paper published online Thursday in Science Express is what may account for the extra weight. Inflammatory signaling can promote a condition called metabolic syndrome, which causes weight gain, high blood pressure and high cholesterol levels and a higher risk for developing diabetes and heart disease.

The fatter mice in Gewirtz's study had been bred to lack a protein known as toll-like receptor 5 (TLR5), which most intestinal cells sprout on their surface. Its job is to recognize and bind to the whiplike flagella that bacteria use to move around. TLR5 acts as a traffic cop for controlling the mass of pathogens living in the intestine; without it, the normally harmless gut bacteria tend to overflourish and expand in number.

When that happens, the study found, it triggers an inflammatory state, as the body attempts to respond to the increasing population of bugs, and at the same time makes cells less sensitive to insulin. In a way, inflammatory factors and insulin compete for the attention of the same intestinal cells; if the cells are busy responding to inflammatory factors, then they are less likely to take up glucose and process it effectively. Such a desensitization to insulin and glucose then leads to the symptoms of metabolic syndrome, such as weight gain, high cholesterol and triglyceride levels and elevated blood pressure — which were all present in the TLR5-deficient mice.

"We don't think the bacteria are directly making the mice eat more, but the bacteria are causing low-grade inflammation, which causes insulin resistance and then makes the mice eat more," says Gewirtz.

To test that theory, the researchers conducted a series of experiments, the most illuminating of which revealed that when the TLR5-deficient mice were given unrestricted diets, they ate 10% more than normal mice, and that even when their food was limited, they were still less sensitive to insulin than their normal counterparts.