Studying the ‘gut-brain axis,’ UNC researchers find evidence of an association between the gut microbiota and the eating disorder.
Researchers at the UNC School of Medicine found that people with anorexia nervosa have very different microbial communities residing inside their guts compared to healthy individuals and that this bacterial imbalance is associated with some of the psychological symptoms related to the eating disorder.
The findings, published today in the journal Psychosomatic Medicine, provide more evidence that the abundance and diversity of the gut microbiota – the trillions of bacteria that affect digestive health and immunity – could also affect the so-called “gut-brain axis.” This research suggests that gut bacteria could play a prominent role in the debilitating symptoms of anorexia nervosa, a serious eating disorder that affects more than 3 million Americans and has the highest mortality rate of any psychological disorder.
“Other studies have linked gut bacteria to weight regulation and behavior,” said Ian Carroll, PhD, senior author of the paper and assistant professor of medicine in the UNC Center for Gastrointestinal Biology and Disease. “Since people with anorexia nervosa exhibit extreme weight dysregulation, we decided to study this relationship further.”
Carroll added, “We’re not able to say a gut bacterial imbalance causes the symptoms of anorexia nervosa, including associated symptoms, such as anxiety and depression. But the severe limitation of nutritional intake at the center of anorexia nervosa could change the composition of the gut microbial community. These changes could contribute to the anxiety, depression, and further weight loss of people with the disorder. It’s a vicious cycle, and we want to see if we can help patients avoid or reverse that phenomenon. We want to know if altering their gut microbiota could help them with weight maintenance and mood stabilization over time.”
For this study, Carroll’s team collected fecal samples from 16 women with anorexia nervosa after they were first admitted into the UNC Center of Excellence for Eating Disorders and then again after their weight was restored – when they were discharged from UNC. Then Susan Kleiman, a graduate student in Carroll’s lab and first author of the paper, characterized the composition and diversity of the gut microbiota in each sample.
Kleiman found significant changes in the gut bacteria populations between admission and discharge. The samples taken at clinic admission had fewer different types of bacteria, making the intestinal communities much less diverse. Microbial diversity is a sign of better overall health. Upon hospital discharge, the microbial diversity had increased, but was still significantly less diverse than that of 12 healthy individuals, whose gut microbiotas were analyzed for this study.
As the microbial communities in patients with anorexia improved during clinical care and weight gain, the moods of patients also improved. Thus, the researchers noted an association between the gut microbiota and a central symptom of people with anorexia nervosa.
The question remains whether improving microbial abundance and diversity could help relieve symptoms related to the eating disorder. To find out, Carroll formed a team of researchers including Cynthia Bulik, PhD, director of the UNC Center of Excellence for Eating Disorders; John Cryan, PhD, professor at University College Cork; Lisa Tarantino, PhD, assistant professor of psychiatry at UNC-Chapel Hill; Anthony Fodor, PhD, a bioinformatics expert at UNC-Charlotte, and Hunna Watson, PhD, a psychologist and biostatistician at UNC-Chapel Hill.
This month, they received a five-year, $2.5-million grant from the National Institutes of Mental Health to further study the relationship between the gut microbiota and anorexia nervosa.
“Over the past 10 years, prominent researchers have learned that when you take gut microbial communities of an obese person and put it in germ-free mice — which are maintained in sterile conditions and lack intestinal microbiota – the mice gain more weight than germ-free mice that have been colonized with a gut microbiota from a lean individual,” Carroll said. “This suggests that gut microbes mediate weight gain or loss.”
Other animal studies showed that adding gut bacteria to previously germ-free mice altered their behavior, especially in relation to anxiety and stress.
“We’re not saying that altering gut bacteria will be the magic bullet for people with anorexia nervosa,” Carroll said. “Other important factors are at play, obviously. But the gut microbiota is clearly important for a variety of health and brain-related issues in humans. And it could be important for people with anorexia nervosa.”
As part of the new NIH grant, his team will characterize the microbiotas of a large number of people with anorexia nervosa as they enter UNC’s clinic and when they are discharged, which typically happens when they reach about 85 percent of their ideal body weight. Then his team will put those gut bacteria in germ-free mice. This will help Carroll learn how the microbiota from anorexia nervosa patients affects the biology and behavior of the mice.
If Carroll’s team learns that the bacteria has a detrimental effect on the mice, then this might suggest that cultivating a healthy microbiota could serve as a therapeutic route to help people with anorexia nervosa.
“Currently available treatments for anorexia nervosa are suboptimal,” Bulik said. “In addition, the process of weight gain and renourishment can be extremely uncomfortable for patients. Often, patients are discharged from the hospital, and within months and sometimes weeks they find themselves losing weight again and facing readmission. If specific alterations in their microbiota could make renourishment less uncomfortable, help patients regulate their weight, and positively affect behavior, then we might see fewer readmissions and more cures.”
Ian Carroll, PhD, is a member of the UNC Center for Gastrointestinal Biology and Disease. Susan Kleiman is a graduate student in the department of nutrition in the UNC Gillings School of Global Public Health and the UNC School of Medicine. Cynthia Bulik, PhD, is Distinguished Professor of Eating Disorders in the Department of Psychiatry.
Funding: The National Institutes of Health and TJ’s Fund for Eating Disorder Research, administered by the Academy for Eating Disorders, supported this research.
Source: Mark Derewicz – UNC
Image Credit: The image is credited to Charlotte Astrid and is licensed CC BY 2.0
Original Research: Abstract for “The Intestinal Microbiota in Acute Anorexia Nervosa and During Renourishment: Relationship to Depression, Anxiety, and Eating Disorder Psychopathology” by Kleiman, Susan C.; Watson, Hunna J.; Bulik-Sullivan, Emily C.; Huh, Eun Young; Tarantino, Lisa M.; Bulik, Cynthia M.; and Carroll, Ian M. in Psychosomatic Medicine. Published online October 1 2015 doi:10.1097/PSY.0000000000000247
The Intestinal Microbiota in Acute Anorexia Nervosa and During Renourishment: Relationship to Depression, Anxiety, and Eating Disorder Psychopathology
Objective: The relevance of the microbe-gut-brain axis to psychopathology is of interest in anorexia nervosa (AN), as the intestinal microbiota plays a critical role in metabolic function and weight regulation.
Methods: We characterized the composition and diversity of the intestinal microbiota in AN, using stool samples collected at inpatient admission (T1; n = 16) and discharge (T2; n = 10). At T1, participants completed the Beck Depression and Anxiety Inventories and the Eating Disorder Examination-Questionnaire. Patients with AN were compared with healthy individuals who participated in a previous study (healthy comparison group; HCG). Genomic DNA was isolated from stool samples, and bacterial composition was characterized by 454 pyrosequencing of the 16S rRNA gene. Sequencing results were processed by the Quantitative Insights Into Microbial Ecology pipeline. We compared T1 versus T2 samples, samples from both points were compared with HCG (n = 12), and associations between psychopathology and T1 samples were explored.
Results: In patients with AN, significant changes emerged between T1 and T2 in taxa abundance and beta (between-sample) diversity. Patients with AN had significantly lower alpha (within-sample) diversity than did HCG at both T1 (p = .0001) and T2 (p = .016), and differences in taxa abundance were found between AN patients and HCG. Levels of depression, anxiety, and eating disorder psychopathology at T1 were associated with composition and diversity of the intestinal microbiota.
Conclusions: We provide evidence of an intestinal dysbiosis in AN and an association between mood and the enteric microbiota in this patient population. Future directions include mechanistic investigations of the microbe-gut-brain axis in animal models and association of microbial measures with metabolic changes and recovery indices.
“The Intestinal Microbiota in Acute Anorexia Nervosa and During Renourishment: Relationship to Depression, Anxiety, and Eating Disorder Psychopathology” by Kleiman, Susan C.; Watson, Hunna J.; Bulik-Sullivan, Emily C.; Huh, Eun Young; Tarantino, Lisa M.; Bulik, Cynthia M.; and Carroll, Ian M. in Psychosomatic Medicine. Published online October 1 2015 doi:10.1097/PSY.0000000000000247