In Vitro Modelling of a Typical Dietary Intake in Restrictive Anorexia Nervosa Results in Changes to Gut Microbial Community and Metabolites

Abstract

Anorexia nervosa (AN) is a psychiatric illness with harmful physical consequences. Studies have observed differences in the faecal microbiota of patients with AN compared to healthy controls. Diet has an impact on the gut microbiota, facilitating an altered community, such changes could impact the gut–brain axis. In this study, a three-stage gut model system that mimics the luminal microbiology of the large intestine was conducted to identify relationships between diet and gut microbiota. A microbial medium was developed to provide nutrients more appropriate to restricting subtype AN (R-AN). The model was inoculated with faeces and samples were taken to compare differences in the microbiota and end products following the fermentation of healthy control medium (HC) compared to R-AN medium. Then, 16S amplicon sequencing along with flow cytometry–fluorescence in situ hybridisation were used to ascertain changes in the microbiota. Gas chromatography (GC) was used to assess changes in microbial metabolites. There were reduced levels of SCFA following the fermentation of R-AN medium. The fermentation of R-AN media led to fewer total bacteria numbers, along with less bifidobacteria and Rumincoccus proximally, but more Clostridium and Enterobacteriaceae. Nutrient-deficient medium resulted in reduced neurotransmitter-producing bacteria, reduced butyrate-producing bacteria, and increased protein-utilising bacteria, all of which could be maintaining factors in AN. The model system provides a novel tool for exploring how extreme dietary changes impact the microbiota and could therefore could be useful for assessing appropriate gut–brain targeted treatments.