Gut microbiota alteration in a mouse model of Anorexia Nervosa.

Abstract

Anorexia Nervosa is a severe disease depending on both biological, psychological and environmental factors. The gut microbiota has recently been proposed as one of the biological factors potentially involved in the onset or maintenance of Anorexia Nervosa. To unravel the potential role of the gut microbiota in this disease, we characterized the dysbiosis occurring in a mouse model of Anorexia and correlated bacteria level changes with different physiological parameters such as body weight, food intake or levels of hypothalamic neuropeptides. We used the Activity-Based Anorexia (ABA) mouse model, which combines food restriction and physical activity, and which mimics core features of Anorexia Nervosa. We characterized the gut microbiota alteration in ABA mice by combining 16S rRNA gene sequencing and quantitative PCR analyses of targeted genera or species. We identified 68 amplicon sequence variants (ASVs) with decreased levels and 8 ASVs with increased levels in the cecal content of ABA mice compared to control mice. We observed in particular in ABA mice increases in the abundance of Clostridium cocleatum and several Lactobacillus species and a decrease in the abundance of Burkholderiales compared to control mice. Interestingly, we show that most of the observed gut microbiota alterations are due to food restriction and are not affected by physical activity. In addition, we identified several bacterial groups that correlate with mice body weight, food intake, lean and fat masses as well as with hypothalamic mRNA levels of NPY (Neuropeptide Y) and POMC (Pro-opiomelanocortin). Our study provides a comprehensive characterization of the gut microbiota dysbiosis occurring in the Activity-Based Anorexia mouse model. These data constitute a valuable resource to further decipher the role of the gut microbiota in the different facets of anorexia pathophysiology, such as functional gastrointestinal disorders, appetite regulation and mood disorders.