The role of gut microbiome in intestinal wound healing Uncovering microbial insights from inflammatory bowel disease and colorectal cancer

The gut microbiome plays a key role in human disease and therapeutic outcomes. While early studies focused on associations, current research increasingly addresses causality, mechanisms, and clinical relevance. This thesis investigates the role of the gut microbiome in intestinal wound healing and its potential for precision medicine. It includes two methodological aims, assessing variation across radial and longitudinal axes, and applying an image-based profiling approach in a human cohort, and three clinical aims focused on Crohn’s disease therapy response, anastomotic leakage, and colorectal cancer recurrence. Microbial communities along the gastrointestinal tract differed by location. Faecal microbiota resembled loosely-adherent mucosal communities, whereas strictly-adherent microbiota formed a distinct niche enriched in oxygen tolerant taxa such as Bacillus and Lactobacillus. In Crohn’s disease, colonic microbiome composition predicted response to anti-TNFα therapy, with Mediterraneibacter gnavus linked to non-response and Blautia to favourable outcomes, supported by functional immune assays. Preoperative microbiome profiling identified Segatella copri as a key factor in anastomotic healing. A two-step model combining microbial composition and metabolic potential accurately stratified leakage risk and outperformed existing clinical tools. Experimental validation in mice supported a protective role for Prevotella like taxa. Additionally, distinct microbial profiles were associated with colorectal cancer recurrence, with Porphyromonas linked to increased risk. Finally, a novel image-based method (SMEAR) enabled rapid microbiome assessment using smartphone images, accurately predicting microbial diversity and key taxa. Overall, this work demonstrates that microbiome informed strategies can improve risk prediction, guide therapy, and support precision medicine in gastrointestinal disease.