The interaction between the gut microbiome and the brain in anorexia nervosa : nutrition, inflammation and brain function in a translational rat model

Trinh, Stefanie Nhu-Binh; Beyer, Cordian (Thesis advisor); Spehr, Marc (Thesis advisor)

Aachen : RWTH Aachen University (2021)
Dissertation / PhD Thesis

Dissertation, RWTH Aachen University, 2021


Anorexia nervosa (AN) is the third most common chronic disease in adolescence and early adulthood. It is a psychiatric disorder characterized by reduced energy intake leading to extreme bodyweight loss, body image disturbances, and pathological fear of gaining weight. Recently, it became clear that the gut microbiome is not only involved in gastrointestinal and metabolic diseases but as well in psychiatric diseases such as major depression disorder. The function of the intestinal microbiome goes far beyond nutrient breakdown and absorption. Itis amongst other relevant for the regulation of the immune system and mood. Moreover, there is evidence that the gut microbiota affect bodyweight and appetite regulation as well as gut permeability and inflammation, all of these seem to be contributing factors to AN. In the present study, the well-established activity-based anorexia (ABA) model was used to investigate fecal microbiota alterations in rats under different conditions of food restrictionand activity levels. Besides this changes in the microbiota diversity and composition were linked with morphological changes of the intestines and brain volume changes in an exploratory manner. Lastly, behavioral alterations especially anxiety-like behavior under food restriction was analyzed and aimed to associate with microbial variations. Our experimental study revealed a clear gut microbiota dysbiosis in food-restricted ratsincluding alterations in the microbiota composition, increased species diversity and changes in specific bacterial genera. In conclusion, we suppose that the driving factor of the observed deviations is food restriction rather than running wheel activity included in the ABA model. Moreover, first associations between gut microbiota changes and brain volume parameters were observed that contribute to prospective research hypothesis. An atrophy of intestinal tissue in food-deprived rats was shown and might lead to an increased gut permeability. Lastly, we showed for the first time that pre-existing anxiety makes rats more susceptible to bodyweight loss in the ABA paradigm possibly facilitated by increased physical activity. In conclusion, the ABA paradigm is additionally useful to investigate gut microbiota alterations in rodents by mimicking microbial dysbiosis similar to patients with AN. To prove the causal effect of the gut microbiome on bodyweight regulation, gut integrity, brain changes and behavior, fecal microbiota transplantation from patients with AN in rodents are needed.