Report Finds Intestinal Ecosystem Directly Affects Anorexia

Unlike what many people may think, anorexia nervosa is not simply about wanting to be thin. In fact, it is a complex mental disorder that changes the way the brain regulates appetite and body image.

In individuals with anorexia nervosa, the brain’s reward system changes, and weight loss becomes its number one priority. This leads to extreme behavioural changes. Among other things, people suffering from anorexia nervosa radically reduce their calorie intake. Around one per cent of all young people develop anorexia nervosa, and in approximately one in five, it becomes a chronic and often life-threatening disease. Nine out of 10 of those diagnosed with anorexia nervosa are females in their teens or early adulthood.

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.

Anorexia nervosa
Nine of 10 who develop anorexia nervosa are females. Girls who develop anorexia nervosa usually do so in puberty when the body begins to change. The young people who develop the disease at the transition between childhood and adulthood consider themselves overweight, even if this is not the case. Concerns about food, exercise, looks and weight turn into obsessions, and the individual begins to eat less and less and exercise more and more and thus starts to lose weight. When the weight is 15 per cent below the standard weight, one may be diagnosed with anorexia nervosa.

After a period of undernutrition, the metabolism and hormonal balances begin to change, as do the parts of the brain regulating appetite, the psyche and behaviour, and the patient increasingly experiences obsessive thoughts, anxiety, fatigue, sleep disorders, stomach symptoms and menstrual disturbances.

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 lead investigator of the study together with Clinical Professor René Støvring, who specialises in anorexia nervosa.

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.

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 behaviour,” 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 counselling and attempts to change the patient’s eating and exercise habits – may benefit from additional treatment aimed at normalising the intestinal microbiome.

“A complex disease like anorexia nervosa calls for personalised and multifactorial treatment. Our findings suggesting 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, provide 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 FMT’s 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.

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.