Anorexia nervosa: can gut dysbiosis contribute to eating disorders?

Anorexia nervosa (AN) affects 1% of the population and about 95% of cases occur in women. The disorder is associated with high morbidity and mortality, and treatment leads to remission in less than half of cases. The causes of AN remain unknown but are thought to include both genetic and environmental factors. By influencing the regulation of appetite, behavior, and emotions via the “gut-brain axis”, the gut microbiota and its metabolites may play a role in the disease. Small-scale studies have already demonstrated dysbiosis of the gut microbiota in patients of the disease.

Profoundly disturbed gut microbiota in women suffering from anorexia

A team from the University of Copenhagen in Denmark used shotgun sequencing of fecal samples and serum metabolome profiling to collect data from 77 female AN patients, then compared the results with data taken from 70 healthy women of the same age. The researchers found that the gut microbiota composition of the women suffering from AN differed from that of the healthy women. In particular, there were reduced levels of the bacterial species Roseburia intestinalis and R. inulinivorans, which are involved in the digestion of plant polysaccharides and are beneficial to health.

In addition, Clostridium species were positively correlated with eating disorders and mental health, suggesting they play a role in the regulation of eating behavior and neuropsychiatric symptoms. Lastly, the gut microbiota of these patients presented higher viral diversity and richness, particularly for Lactococcus phages. 
The serum metabolome of AN patients also showed significant differences from that of healthy women. The researchers observed an increase in several bile acids, including indole-3-propionic acid, a metabolite associated with the secretion of glucagon-like peptide 1, which stimulates satiety and slows gastric emptying. Causal inference analyses by the team suggest that bacterial metabolites mediate some of the effects of gut dysbiosis on eating disorders.

Reduced weight gain and altered energy metabolism in mice

The researchers then took germ-free (sidenote: Germ-free mice mice that have no microbes at all, raised in sterile conditions. ) emice on a calorie-restricted diet and gave them a fecal microbiota transplant from either the AN women or the healthy women (control mice). After three weeks of a 30% reduction in food intake (to mimic the eating behaviors of anorexia patients), the mice given fecal samples from the AN women had a greater initial weight loss and slower weight regain than the control mice. Furthermore, there was a higher expression of appetite suppressor genes in the hypothalamus of the AN-transplanted mice and of thermogenesis-related genes in their adipose tissue.