Whole Gut Microbiome Sequencing in Patients With Anorexia Nervosa

BACKGROUND Anorexia nervosa (AN) is a complex disorder characterized by disturbed body image, ego-syntonic neglect, ambivalence, self-starvation, loss of body weight, obsessive thoughts of food, ritualistic patterns of food intake, elevated physical activity, depression, anxiety and emotional rigidity. The evidence base for the treatment is very limited, considering the extent to which this disorder erodes quality of life and still carries the highest fatality rate of any psychiatric diseases. In fact, there is no evidence that the prognosis has improved throughout the 20th century.

AN remains a syndrome, i.e. collections of symptoms, as it is not defined by etiology. Twin studies have consistently demonstrated that AN is strongly familial predominantly due to genetic factors. However, neither candidate gene nor genome-wide studies have identified truly validated genes for AN. AN is associated with multiple, profound endocrine disturbances. However, so far the extensive research has not led to any breakthrough discovery. There is a need for new thinking.

Colonization of the human gut begins at birth with bacteria from the mother's vagina and labor-released maternal feces. In adults the human digestive tract contains complex assemblies of microorganisms which actually outnumber the number of the host cells 10:1. This intestinal microbiota and its microbiome provide humans with additional gene products, which may be regarded as an organ, which contributes to multiple host metabolic pathways. Thus, a whole range of substances are produced which are not yet identified. Potentially some of these substances may affect functions in the brain, such as appetite and emotion regulations. Recent advances in microbial DNA sequencing technologies have resulted in metagenomics DNA analysis of whole ecosystems such as the human gut. An important step forward in investigating the bacterial composition of the human microbiome was taken with the Metagenome of the Human Intestinal Tract consortium reporting the first complete microbial gene atlas of the human distal gut, using deep next generation metagenome sequencing.

AIM To investigate whether gut microbiota is altered in patients with AN. If confirmed, this potentially may play a role in the pathogenesis, promoting susceptibility to development and/or maintenance of AN.

HYPOTHESIS Patients with AN harbor an altered gut microbiota composition and functional potential as determined by quantitative metagenomic analyses of microbial DNA isolated from stool samples and sequenced applying a combination of deep and untargeted shotgun sequencing.