A study in mice done by the University of Iowa illustrates that drug-induced shifts in the gut microbiome can result in obesity by lowering the resting metabolic rate – the rate at which calories are burned while resting or sleeping. Published in the journal eBiomedicine, the findings highlight the vital role of gut microbes in energy balance and indicate that unhealthy microbiome changes can result in weight gain and obesity by changing resting metabolism.
Professor of microbiology and urology at the UI Carver College of Medicine, John Kirby, Ph. D, stated that their research points to the conclusion that it is likely gut bacteria that are responsible for calories burnt while you sleep.
Kirby and his colleagues concentrated on the impacts of risperidone, an antipsychotic drug that results significant weight gain in patients. Risperidone is utilized in treatment of various psychiatric disorders in children and adults, including bipolar disorder, autism and schizophrenia, and prescribing rates for children have multiplied almost eight-fold over the last twenty years.
Kirby and UI pediatric psychiatrist, Chadi Calarge, in a earlier study compared patients taking risperidone long-term to patients who were not using the drug. They discovered that weight gain corresponded with a significant change in the composition of the patient’s gut microbiomes. The results were published in Translational Psychiatry.
In the recent eBiomedicine study, Kirby teamed up with UI assistant professor of pharmacology, Justin Grobe, to pinpoint how this risperidone-induced gut microbiome change causes weight gain. Reflecting the human studies, the researchers illustrated that risperidone causes weight gain in mice (over two months, 2.5 grams, or roughly 10% of the total body mass, compared to controls) and remarkably changes the bacterial composition of the mouse gut microbiome. They then illustrated that the changed gut microbiome causes a decrease in resting metabolic rate that is completely responsible for the excess weight gain.
Kirby stated that the control mice gained little weight as they aged and their gut microbiome underwent a healthy change due to aging. With the risperidone, the mice became obese and showed an alternative, less healthy change in their gut microbiome. He added that with this study, they now have a mechanism for how a change in the gut microbiome contributes to weight gain, and it’s to do with alterations to the resting metabolic rate.
The team was able to examine how the gut microbiome change affected the mice’s metabolism by using a novel piece of equipment invented by Grobe – a total calorimetry machine. The instrument enables precise measurements of oxygen consumption, heat production, carbon dioxide output and energy intake in a single animal to establish the total energy change, or “delta G,” of the mouse.
The researchers found that there was no shift in oxygen-dependent resting metabolic rate for mice fed risperidone compared to the control mice, but there was a remarkable decrease in non-aerobic resting metabolic rate enough to account for the mice’s weight gain.
Grobe stated that it would be 29 pounds of fat gain each and every year for the average human. Kirby added that it is the equivalent of consuming one additional cheeseburger every single day.
The findings may indicate that manipulating resting metabolic rate, especially by targeting the gut microbiome, could represent a new strategy to treating obesity. Alternatively, preventing unhealthy shifts to the gut microbiome may prove advantageous for patients undergoing risperidone treatment.