Microbial alchemy in ulcerative colitis Crafting the recipe for fecal microbiota transplantation

This thesis explores the therapeutic potential of fecal microbiota transplantation (FMT) in ulcerative colitis (UC), an inflammatory bowel disease with rising incidence. It is structured into three parts.
Part 1 addresses the scientific rationale and methodology behind FMT. It demonstrates that higher bacterial alpha-diversity in both donors and recipients is associated with improved clinical response. It also shows that anoxic processing of donor feces preserves obligate anaerobes better than standard anaerobic methods, potentially enhancing treatment efficacy.
Part 2 focuses on the practical application of FMT in UC. It presents the protocol of the TURN2 trial, a randomized controlled study integrating donor selection based on microbiota profiles and anaerobic stool processing. It also provides insights into the challenges and costs of donor screening at Amsterdam UMC, underscoring the need to develop donor-independent microbiota-based therapies.
Part 3 investigates microbial interactions beyond bacteria. It shows that the protozoa Blastocystis spp. and Dientamoeba fragilis are more prevalent in healthy individuals than UC patients, and their presence correlates with higher bacterial diversity and lower yeast overgrowth. These findings question the routine exclusion of these organisms in donor screening and highlight the need to better understand their ecological role in the gut.
Together, the studies in this thesis aim to advance FMT towards a more effective, evidence-based, and ecologically informed treatment strategy for UC.