Exclusive enteral nutrition therapy reduces Clostridia flagellins within the Crohn’s disease gut microbiome
Crohn’s disease is a highly prevalent form of inflammatory bowel disease, with rapidly increasing incidence both within New Zealand, and around the world. Although Crohn’s disease aetiology is poorly understood, it has been linked to the host gut microbiome, alongside a range of host genetic and environmental factors. Temporary Crohn’s disease remission can be induced by exclusive enteral nutrition, which has previously been hypothesised to be effective through direct alteration of the gut microbiome. This treatment method avoids many of the substantial side effects associated with traditional Crohn’s disease treatments, such as corticosteroids. In this study, 16S rRNA and whole genome sequencing of stool samples, alongside measurement of stool short-chain fatty acid content, were used to measure the impact of exclusive enteral nutrition and partial enteral nutrition on the gut microbiomes of both adult Crohn’s disease patients and healthy controls. Exclusive enteral nutrition altered beta diversity and taxonomic composition, as well as functional capacity and short-chain fatty acid production, within both Crohn’s disease and healthy gut microbiomes. Perturbation of species belonging to the Clostridia class dominated the taxonomic changes observed both with Crohn’s disease, and during exclusive enteral nutrition. These changes were predominantly transient, with the gut microbiomes of both Crohn’s disease patients and healthy people largely rebounding after treatment. There were no changes to the gut microbiome observed during partial enteral nutrition, and no changes in alpha diversity observed during any form of enteral nutrition. Exclusive enteral nutrition reduced the capacity of the gut microbiome to produce flagella, through perturbation of species belonging to Clostridium cluster XIVa. Through analysis of the role played by commensal Clostridia class species in the guts of Crohn’s disease patients, a novel model of Crohn’s disease aetiology was developed, implicating Clostridium cluster XIVa flagellin proteins CBir1 and Fla-X. This model describes an inflammatory immune response to CBir1 and Fla-X present in the gut, where normal regulation by regulatory T cells is lost. This model may allow for the investigation of novel Crohn’s disease treatments.
Advisor: Morgan, Xochitl
Degree Name: Master of Science
Degree Discipline: Microbiology and Immunology
Publisher: University of Otago
Keywords: Crohn's disease; Enteral nutrition; Exclusive enteral nutrition; Gut microbiome; Flagellins; Clostridia; CBir1; Bioinformatics
Research Type: Thesis