Changes to Gut Microbiome Influence Risk for Obesity, Metabolic Disease

New research uncovering the mechanism that controls hunger could lead to obesity drugs. Lucas Jackson/REUTERS

Research on the microbiome continues to prove the age-old claim that "you are what you eat." Countless studies suggest the trillions of tiny bugs that make their home in a person's gut have some influence on nearly every aspect of health, especially the likelihood of becoming severely overweight and developing obesity-related conditions such as heart disease and diabetes.

A new study published June 8 in Nature suggests altering the makeup of gut microbes could be an effective way to address weight and related problems. Though plenty of researchers have made this claim before, this is the first study to specifically identify the mechanism by which changes in a person's gut microbes influences the likelihood for developing obesity and metabolic syndrome, a cluster of conditions that include high blood pressure, high blood sugar, excess body fat around the waist and abnormal cholesterol levels.

In studies on mice, researchers at the Yale University School of Medicine found that acetate, a short-chain fatty acid, is responsible for modulating the production of insulin in rodents. They compared the effects of acetate and other short-chain fatty acids and discovered that mice with higher levels of acetate were more likely to consume a high-fat diet. To further confirm the connection, the researchers then infused acetate into a group of rodents to see whether it would cause the animals to put on weight. They observed that injecting the rodents with acetate stimulated insulin secretion by the pancreas. Higher levels of insulin increases the storage of fat and prevents the body from releasing it for energy production.

Next, they injected acetate directly into the brains of these rodents. This caused an increase in insulin production and stimulated the secretion of gastrin and ghrelin, two hormones that are known to increase food intake.

To more closely identify the link between altered gut microbes and changes in appetite and eating behaviors, the researchers transferred fecal matter from a group of obese rodents to healthy rodents. That caused changes in the gut microbes of the healthy mice, and changes in acetate and insulin levels that could result in obesity.

There is some anecdotal evidence suggesting these findings could apply to humans, as well. Last year, the journal Open Forum Diseases published a case study of a 32-year-old woman treated for C. difficile infection with fecal transplantation. In this experimental treatment, poop from a healthy individual is transplanted to a person with this antibiotic-resistant bacterial infection—the idea being that the new, good microbes will crowd out the lethal ones. Transplanting healthy stool, either through capsules or colonoscopy, has more than a 90 percent success rate for clearing C. difficile infections.

The young woman in the experiment recovered from the infection—but she also quickly put on 36 pounds, and her BMI rose from 26 to 33 in a little over a year after the transplant. Her physicians suspected the fecal transplant was most likely the cause of her weight gain, thereby showing the bugs in the gut may very well determine the girth of one's belly.