Microbiota-derived metabolites in intestinal disease

Summary

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The human gastrointestinal tract is inhabited by trillions microbial cells that mostly form a symbiotic relationship with the host. Out of these microbial cells, bacteria have been studied best with regard to the function and effects in the intestinal tract. To this end, several bacterial species have been identified to directly or indirectly contribute to intestinal pathologies, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). Recent focus has shifted to the contribution of bacteria-derived metabolites, the intermediate or end products of metabolic reactions, on the intestinal tract. In this work, we aimed to further delineate the contribution of microbiota-derived metabolites on the intestinal diseases IBD and CRC.

The research conducted in this thesis provides insight into the consequences of two bacterial-derived metabolites ADP-heptose and butyrate on especially the intestinal epithelium. This is accomplished using to pathogenic bacterial species F. nucleatum and C. jejuni, which additionally provides insights into pathogenic mechanisms employed by these bacterial species. The results expand our knowledge on microbiota-derived metabolites in intestinal diseases such as inflammatory bowel disease, colorectal cancer and acute gastroenteritis as result of C. jejuni infection. Additionally, the research allows for identification of novel therapeutic approaches to combat these metabolites or bacteria in these diseases.