Exploring the gut-blood metabolome across species and countries

Abstract

The gastrointestinal tract is essential for the proper functioning of organisms. Not only does it play a role in the absorption of nutrients and water, but it also forms a barrier that keeps out potentially harmful microorganisms. If the gut is chronically inflamed, as commonly seen in inflammatory bowel disease (IBD) and farm animals, overall health and quality of life are severely decreased. In many cases, no clear cause can be found, and the subsequent infections often require antibiotics, which is undesirable given the growing global problem of antibiotic resistance. This inflammation impacts nutrient absorption alongside the bacteria living in the gut and the molecules they produce. In this thesis, we investigate if these changes can be measured in blood. Changes in these molecules, metabolites, can tell us something about underlying causes and consequences of reduced gut health. To find these changes, we developed the software tool MetaboShiny. To find patterns involving multiple metabolites, we used artificial intelligence. We uncovered which metabolites were good predictors and thus potentially involved in cause and consequence of inflammation. When investigating these metabolite signatures on the level of metabolic processes in chickens and IBD patients, we observed that many metabolites were involved in amino acid metabolism. In IBD patients with simultaneous inflammation of the bile ducts, we compared our findings to known blood metabolome changes associated with shifts in the gut microbiome. The results suggest unfavourable changes in gut bacterial composition.