A drug that helps your mind may turn your gut microbes—and waistline—against you.

In a series of experiments in mice, researchers found that a common drug used to treat psychiatric illnesses, including autism and bipolar disorder, alters the gut microbial community. Those changes caused the mice to burn fewer calories while resting and gain weight, researchers report in EBioMedicine. The finding, which lines up with weight gain seen in patients, suggests that drugs other than antibiotics can easily mess with a person’s microbes, which in turn profoundly influence metabolism, weight, and overall health.

In the study, researchers led by microbiologist John Kirby of the University of Iowa gave mice water laced with the psychiatric drug risperidone. This drug is well-known to cause significant weight-gain, insulin resistance, and metabolic problems in people. Kirby and colleagues had a hunch that the hefty side-effects were linked to changes in the gut microbiome, but they were unsure of the exact mechanism.

In the study, the risperidone-drinking mice also gained weight—an average of 10 percent of their normal body mass in just two months. And when researchers sequenced the microbes in the mice's poop, they found that the microbial communities in the animals’ intestinal tracts were dramatically altered.

By measuring energy intake, oxygen consumptions, carbon dioxide release, and heat production, the team found that the drug-dosed mice were burning fewer calories while resting and sleeping compared to normal mice. In fact, the drug-dosed mice were burning about 16 percent fewer calories. That would be equivalent to a person on a standard 2,000 calorie-a-day diet eating a McDonald's cheeseburger everyday in addition to their normal diet, which would lead to about a 29-pound weight gain over a year, the authors note.

After some calculations, the researchers found that the lower calorie-burning rate matched up with the weight gain they saw in the mice.

To fatten the link between the microbial changes and the metabolic changes, the researchers transplanted microbe-loaded poop from the drug-dosed mice into normal mice that never had risperidone. Those normal mice then gained weight and burned fewer calories, just like the drug-dosed animals. (The researchers noted that the poop did not contain much of the drug itself, only about 0.001 percent of the original dose. This strengthens their conclusion that the microbial communities themselves led to the metabolic changes.)

When the researchers transferred just the gut viruses from the drugged mice to healthy mice, the researchers reported that healthy mice again gained weight. Lastly, in petri-dish experiments, risperidone inhibited certain microbes that grow in the gut.

“Collectively,” the authors conclude, “these data highlight a major role for the gut microbiome in weight gain following chronic use of risperidone.” The authors hope that the finding could spur the development of drugs that could protect healthy gut microbe populations and thus fend off metabolic disorders.

EBioMedicine, 2015. DOI: 10.1016/j.ebiom.2015.10.018 (About DOIs).