Origins Of Eating Disorders Found In Gut Microbe

The incidence of eating disorders such as anorexia nervosa is somewhere between 5 to 10% of the population but there is very little understanding of the mechanism that is the source of the disease.  Given that mood disorders such as depression and schizophrenia have biochemical roots, speculation is that eating disorders can be traced to a similar cause. 
 
Now researchers at the French Institute of Health and Medical Research and the University of Rouen in France have found strong evidence that a protein made by intestinal bacteria are a causative agent for the disorders.  Specifically, antibodies made by the host against this protein cross-react with a mammalian satiety hormone.  The severity of symptoms in ED patients was also found to correlate with levels of the neutralizing antibodies.  The researchers believe that this understanding will ultimately lead to a chemical therapeutic strategies to correct eating disorders. 
 
The scientists focused on a known mammalian modulator of feeding behavior, the protein α-MSH, known variously as alpha-Melanocyte-stimulating hormone and alpha-melanotropin among other names.  α-MSH has been implicated in EDs.  Using a molecular “fishing” tool, they pulled from the common mammalian gut microbiome inhabitant E. coli K12 a “mimetic”, a protein that is very similar to human α-MSH, called ClpB.
 
Next, the researchers checked how a host responds to dosages of ClpB.  Mice which were dosed with ClpB indeed lost weight briefly but a month later increased their weight by 5%.  These mice remarkably also became immune to α-MSH, which usually induces anorexic-like effects.  In summary, these results show that ClpB provokes a feeding or energy usage reaction in the host that at early times looks like weight loss but at later times weight gain.
 
To understand the link between bacterial ClpB and host α-MSH, the researchers verified that administering ClpB in the mice provoked an immune reaction not only to ClpB itself, but to the similar protein α-MSH.  This means that host produces antibodies to the bacteria that inadvertently hit its own α-MSH, a regulator of feeding, energy regulation and anxiety.