New Research Unveils the Gut’s Surprising Role in Anorexia

Using DNA technology and advanced bioinformatics analyses, the researchers identified distinct and marked changes in composition and function of the intestines’ trillions of bacteria and viruses in cases with anorexia nervosa. Credit: Søren Vestergaard/University of Copenhagen

Contrary to common belief, anorexia nervosa is not just a desire to be skinny. Rather, it is a complicated mental illness that alters the brain’s control over hunger and self-perception of one’s body.

Individuals with anorexia nervosa experience a transformation in their brain’s reward mechanism, making weight loss their primary focus. This results in drastic behavioral changes, including a drastic reduction in caloric intake. Approximately 1% of young people develop anorexia nervosa, and for about one in five, it becomes a chronic and potentially fatal condition. The majority of those diagnosed with anorexia nervosa are young females in their teenage years or early adulthood, accounting for about 90% of cases.

The incidence of anorexia nervosa is too upward.

The disease is caused by a complex interaction between various so-called vulnerability genes and environmental influences. However, it now also appears to be a result of a severe imbalance in the intestinal ecosystem of trillions of bacteria and viruses.

This is the conclusion of a new study conducted by an international team headed by Danish scientists. The study involved 77 Danish girls and young women suffering from anorexia nervosa and 70 healthy individuals of the same gender. The results suggest that severe changes in the intestinal microbes and corresponding gut microbiome-produced metabolites in the blood may directly affect the development and retention of anorexia nervosa.

To demonstrate this, the researchers transplanted stools from anorexia cases and healthy individuals, respectively, to bacteria-free mice, explains Professor and Principal Investigator Oluf Borbye Pedersen from the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen.

“The mice receiving stools from individuals with anorexia nervosa had trouble gaining weight, and analyses of gene activities in certain parts of their brain revealed changes in various genes regulating appetite. In addition, the mice that had been given stools from individuals affected with anorexia nervosa showed increased activity of genes regulating fat combustion likely contributing to their lower body weight,” explains Oluf Pedersen, who is the lead investigator of the study together with Clinical Professor René Støvring, who specializes in anorexia nervosa.

Intestinal bacteria produce reduced amounts of important vitamin

Using DNA technology and advanced bioinformatics analyses, the researchers identified distinct and marked changes in the composition and function of the intestines’ trillions of bacteria and viruses in cases with anorexia nervosa.

Researchers compared the disruptions of the gut microbiome with blood molecules (metabolites) produced by the gut microbiome demonstrating associations between specific changes of the gut bacteria, blood bacterial molecules, and a number of personality traits such as distorted body image, drive for thinness, and refusal to eat in those affected by anorexia nervosa.

“We also discovered that specific gut bacteria in women with anorexia nervosa produce less vitamin B1. Deficiency of B1 may lead to loss of appetite, various intestinal symptoms, anxiety, and isolating social behavior,” says Assistant Professor Yong Fan from the Novo Nordisk Foundation Center for Basic Metabolic Research, a leading young researcher of the study.

“Moreover, our analysis of the intestinal microbiome revealed in anorexia cases different virus particles able to decompose lactic acid-producing bacteria in the intestines. Both findings may form the basis of future clinically controlled trials with B1 vitamin supplements and fermented food or probiotics containing various types of lactic acid bacteria,” he says.

Years of clinically controlled studies are ahead

The new study is an example of basic research meant to explore whether a disturbed microbial ecosystem of the gut is a contributory factor in the development or retention of a chronic disease. And this may potentially be the case for anorexia nervosa.

The next question is whether basic research can lay the foundation for clinically controlled trials exploring if current treatment for anorexia nervosa – involving psychotherapy, family counseling, and attempts to change the patient’s eating and exercise habits – may benefit from additional treatment aimed at normalizing the intestinal microbiome.

“A complex disease like anorexia nervosa calls for personalized and multifactorial treatment. Our findings suggest that disruptions of the communities of gut bacteria and viruses and their functions as mirrored in altered microbiome-synthesized blood metabolites may be involved in the development and retention of the disease, providing a rationale for initiating clinically controlled trials. In such trials, clinical investigators will likely test the potential effects of an initial antibiotics intervention to reset the aberrant gut microbiome followed by weekly fecal microbiota transplantation (FMT) from young healthy donors for months. Such FMTs might be supplemented with B1 vitamin and multistrain probiotics. Whether interventions like the suggested will qualify for future adjunctive therapy to current conventional intervention, remain to be shown”, says Oluf Pedersen.

Reference: “The gut microbiota contributes to the pathogenesis of anorexia nervosa in humans and mice” by Yong Fan, René Klinkby Støving, Samar Berreira Ibraim, Tuulia Hyötyläinen, Florence Thirion, Tulika Arora, Liwei Lyu, Evelina Stankevic, Tue Haldor Hansen, Pierre Déchelotte, Tim Sinioja, Oddny Ragnarsdottir, Nicolas Pons, Nathalie Galleron, Benoît Quinquis, Florence Levenez, Hugo Roume, Gwen Falony, Sara Vieira-Silva, Jeroen Raes, Loa Clausen, Gry Kjaersdam Telléus, Fredrik Bäckhed, Matej Oresic, S. Dusko Ehrlich and Oluf Pedersen, 17 April 2023, Nature Microbiology.
DOI: 10.1038/s41564-023-01355-5

The international research team comprised Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen, the University of Southern Denmark and Odense University Hospital, Aalborg University Hospital, Aarhus University Hospital, the National Research Institute for Agriculture, Food and Environment in France, Center for Microbiology, VIB, Leuven, Belgium, University of Gothenburg and Ørebro University in Sweden, Turku University in Finland and Leiden University in the Netherlands.