May 16, 2019

Dr. Ian Carroll

Dr. Ian Carroll

Ian Carroll, PhD, assistant professor in the Department of Nutrition at the UNC Gillings School of Global Public Health, is entering the final year of a $2.3 million grant to study how the intestinal microbiota impacts anxiety and weight regulation, two factors that influence the development of the eating disorder anorexia nervosa.

The intestinal microbiota is the largest microbial community in the human body, comprising bacteria, fungi, archaea and viruses. In 2015, Carroll was awarded a five-year grant from the National Institute of Mental Health (NIMH) for his study “Microbiome-mediated weight, anxiety and stress dysregulation in anorexia nervosa.”

Anorexia nervosa is an eating disorder characterized by extreme weight-loss behaviors, severely low body weight and intense fear of weight gain, in addition to a constellation of other potential psychiatric and physiological symptoms. With the knowledge that the complex microbial community in the intestine can be both beneficial and detrimental to human health in a number of ways, Carroll and his team are exploring how intestinal microbes impact weight regulation and high levels of anxiety.

“We believe that a person’s intestinal microbiota doesn’t cause this disease, but if you don’t nourish yourself, you aren’t nourishing your microbes,” said Carroll. “When the composition of your intestinal microbiota changes, it can influence behavior and how you gain weight—which is obviously relevant in the context of clinically re-nourishing patients with anorexia nervosa.”

One of the study’s methods includes introducing human fecal microbes to germ-free mice. Once the mice have been colonized with human microbes, Carroll’s team then observes how a person’s microbiome influences behaviors and fat accumulation in the mice.

“By nature, germ-free mice eat more food and put on less fat than mice raised with a ‘conventional’ suite of microbes,” Carroll said. “Previous studies have demonstrated that when you transplant an intestinal microbiota from an obese person into one group of mice and a lean microbiota into the other group, the mice receiving microbes from the obese person store more fat while eating the same diet as the lean-microbe mice.”

Germ-free mice also exhibit lower levels of anxiety and a higher threshold for stress. The introduction of certain intestinal microbes has been shown to alter those anxiety and depression levels. As anorexia nervosa is characterized by both weight dysregulation and anxiety, the intestinal microbiota potentially could be targeted to treat the disease more effectively.

Carroll’s group, in collaboration with Cynthia Bulik, PhD, FAED, Gillings School professor of nutrition and the founding director of UNC’s Center of Excellence for Eating Disorders, will next conduct an early Phase I clinical trial to study fecal microbiota transplantation in people. His team will transplant fecal microbes from healthy human donors into patients with anorexia nervosa to see if the procedure impacts their mood and weight restoration processes to support successful re-feeding and help the patients recover more quickly.

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