Anorexia/bulimia: A bacterial protein implicated

Eating disorders (ED) such as anorexia nervosa, bulimia, and binge eating disorder affect approximately 5-10% of the general population, but the biological mechanisms involved are unknown. Researchers at Inserm Unit 1073, “Nutrition, inflammation and dysfunction of the gut-brain axis” (Inserm/University of Rouen) have demonstrated the involvement of a protein produced by some intestinal bacteria that may be the source of these disorders. Antibodies produced by the body against this protein also react with the main satiety hormone, which is similar in structure. According to the researchers, it may ultimately be possible to correct this mechanism that causes variations in food intake.

These results are published in the journal Translational Psychiatry, in the online issue of 7 October 2014.

Anorexia nervosa, bulimia and binge eating disorder are all eating disorders (ED). If the less well defined and atypical forms are included, ED affect 15-20% of the population, particularly adolescents and young adults. Despite various psychiatric, genetic and neurobiological studies, the molecular mechanism responsible for these disorders remains mysterious. The common characteristic of the different forms of ED is dysregulation of food intake, which is decreased or increased, depending on the situation.

Sergueï Fetissov’s team in Inserm Joint Research Unit 1073, “Nutrition, inflammation and dysfunction of the gut-brain axis” (Inserm/University of Rouen), led by Pierre Déchelotte, studies the relationships between the gut and the brain that might explain this dysregulation.

The mimic of the satiety hormone

In this new study, the researchers have identified a protein that happens to be a mimic of the satiety hormone (melanotropin). This protein (ClpB) is produced by certain bacteria, such as Escherichia coli, which are naturally present in the intestinal flora. Where this protein is present, antibodies are produced against it by the body. These will also bind to the satiety hormone because of its structural homology to ClpB, and thereby modify the satietogenic effect of the hormone. The sensation of satiety is reached (anorexia) or not reached (bulimia or overeating). Moreover, the bacterial protein itself seems to have anorexigenic properties.

Variations in food intake in the presence of the bacterial protein

To obtain these results, the researchers modified the composition of the intestinal flora of mice to study their immunological and behavioural response. Food intake and level of antibodies against melanotropin in the 1st group of mice, which were given mutant E. coli bacteria (not producing ClpB) did not change. In contrast, antibody level and food intake did vary in the 2nd group of animals, which received E. coli producing ClpB protein.

The likely involvement of this bacterial protein in disordered eating behaviour in humans was established by analysing data from 60 patients.

The standardised scale “Eating Disorders Inventory-2” was used to diagnose these patients and evaluate of the severity of their disorders, based on a questionnaire regarding their behaviour and emotions (wish to lose weight, bulimia, maturity fears, etc.). Plasma levels of antibodies to ClpB and melanotropin were higher in these patients. Furthermore, their immunological response determined the development of eating disorders in the direction of anorexia or bulimia.

These data thus confirm the involvement of the bacterial protein in the regulation of appetite, and open up new perspectives for the diagnosis and specific treatment of eating disorders.

Correcting the action of the protein mimicking the satiety hormone

"We are presently working to develop a blood test based on detection of the bacterial protein ClpB. If we are successful in this, we will be able to establish specific and individualised treatments for eating disorders," say Pierre Déchelotte and Sergueï Fetissov, authors of this study.

At the same time, the researchers are using mice to study how to correct the action of the bacterial protein in order to prevent the dysregulation of food intake that it generates. “According to our initial observations, it would indeed be possible to neutralise this bacterial protein using specific antibodies, without affecting the satiety hormone,” they conclude.

Brain Stimulation May Treat Bulimia

A mild electrical stimulation to a specific brain area could be an effective treatment for some patients with eating disorders such as bulimia, who suffer from episodes of severe binge eating and purging behaviors, researchers say.

After one 42-year-old woman received the electrical stimulation, called transcranial magnetic stimulation (TMS), as a treatment for her depression, and showed an unexpected recovery from her 20-year battle against bulimia nervosa, her doctors conducted a pilot study to see whether the treatment would also work for other patients with eating disorders, said Dr. Jonathan Downar, of the University of Toronto. Downar described the study Tuesday (Nov. 12) here at the annual meeting of the Society for Neuroscience.

In the study, Downar and his colleagues recruited 20 patients with bulimia and stimulated a part of their frontal lobes called the dorsomedial prefrontal cortex, which is next to the brain region usually stimulated for treating depression. The patients, who had already tried conventional therapies and medications but had seen no improvement, received 20 sessions of electrical stimulation daily for four weeks.

At the end of the treatment, six of the patients saw their binge eating and purging symptoms almost completely disappear. In another four patients, symptoms improved by more than 50 percent. Eight patients saw only little improvement, and two got worse, Downar said.

Although larger studies and clinical trials are needed to confirm the results of the pilot study, Downar said he is optimistic about the promise of using TMS for treating certain patients with eating disorders.

"There are lots of things you could do to treat disorders like depression, but for these folks [with bulimia], there’s really nothing if they have gone through all of the medications" and therapy options, Downar said.

Eating disorders, such as anorexia and bulimia, affect more than 8 million people in North America. These disorders often carry emotional distress, disrupt the person’s normal life and can even lead to life-threatening medical problems.

TMS is a relatively new technique, and involves a large electromagnetic coil that is placed over the skull, and changes the activity in a targeted brain region by inducing electric currents. Although the change is temporary and reversible, with repeated stimulation, doctors can create lasting changes in neuronal activity. Repeated TMS has been approved by the U.S. Food and Drug Administration as a treatment for some forms of depression.

In the study, the researchers used brain imaging to examine whether differences in brain activity could explain why some patients respond well to TMS treatment while others show little or no improvement.

They found that before the treatment, responders had lower connectivity between the frontal lobe and a set of brain areas (such as the striatum) that are linked to rewards and cravings. This low connectivity could be a sign of impulsiveness, and stimulation may have helped to make the missing connection in these patients’ brains, Downar said.

In contrast, the brains of the people whose bulimia was not helped by TMS appeared more connected in those areas. In these patients, TMS appears to be ineffective in treating bulimia because the brain stimulation is “giving them something they don’t need, because they already have it,” Downar said.

The brain imaging results suggest that doctors may be able to identify which patients will respond to TMS treatment, and spare others from a weeks-long treatment.

"By using brain imaging to detect these patterns, we may eventually be able to predict which patients are most likely to benefit," Downar said.