Biological mechanisms of eating disorders

Anorexia nervosa and bulimia are two main forms of eating disorders. Although biological mechanism of eating disorders is still unknown, it is now clear that these disorders are accompanied by altered functions of the brain circuitries involved in regulation of appetite and emotion 1. Among the pathophysiological mechanisms which may contribute to the brain abnormalities in eating disorders, is an altered function of the adaptive immune system which normally participates in adaptation to stress and may provide a link between the gut and the brain. In particular, altered production of autoantibodies (autoAbs) directed against α-melanocyte stimulating hormone (α-MSH), a key neuropeptide involved in regulation of appetite, emotion and stress, can underlie several clinical characteristics of eating disorders 2.

In fact, although α-MSH autoAbs are normally presents in healthy humans and animals, their production is influenced by stress resulting in changing of their properties which can be physiological or pathological. E.g. repeated mild stress in animals induces more high affinity α-MSH autoAbs resulting in reduced anxiety and increased food intake. In contrast, acute strong stress induces production of low affinity α-MSH autoAbs which do not show blocking function but, instead, show anorexigenic and anxiogenic properties.
Involvement of α-MSH autoAbs in eating disorders is further supported by findings of increased binding of α-MSH autoAbs from sera of patients with eating disorders to α-MSH neurons in the brain and significant associations between serum levels of α-MSH autoAbs and psychopathological symptoms revealed by the Eating Disorders Inventory. Importantly, such correlations are opposite between anorexia and bulimia suggesting that changes of α-MSH autoAbs properties may be responsible for the switch between anorectic and bulimic stages of the eating disorder.

Since α-MSH autoAbs are normally present in healthy individuals but their properties could be altered in subjects with eating disorders, it is necessary to identify the mechanisms responsible for this alteration. Proteins from several microorganisms display sequence homology with α-MSH among which there are commensal and pathogenic bacteria present in gut microflora. Thus, it is possible that certain microorganisms can trigger production of autoAbs having different properties to interact with α-MSH resulting in stimulation or inhibition of appetite. It also implies that nutrition, including pre- and probiotics having impact on the composition of the gut microflora may influence production of autoAbs directed against α-MSH which in turn may influence α-MSH-mediated satiety and anxiety. If existence of this link will be further validated, it may provide a background for development of new therapeutic strategies of eating disorders.


References

1. Kaye WH, Fudge JL, Paulus M. New insights into symptoms and neurocircuit function of anorexia nervosa. Nat Rev Neurosci 2009;10:573-584.

2. Fetissov SO, Déchelotte P. The putative role of neuropeptide autoantibodies in anorexia nervosa. Current Opinion in Clinical Nutrition and Metabolic Care 2008;11:428-434.