Exploring the role of the microbiota: in defence against Clostridioides difficile and multidrug resistant Gram-negatives

Antibiotics provided humanity resilience to the majority of bacterial infections. An important trade-off is the emergence of antimicrobial resistance, and a diminished and perturbed microbiota, resulting in an increased susceptibility for Clostridioides difficile infections. For both C. difficile and multidrug resistant micro-organisms (MDRO), asymptomatic colonisation of the gut plays an important role in the development of infection. The aim of this thesis is to better understand the role of the microbiota in defence against infections with C. difficile and MDRO. The first part describes the epidemiology and detection of asymptomatically colonized individuals. It concludes that though asymptomatic colonization of MDRO and C. difficile can become a nidus for nosocomial (hospital) infection and transmission, its prevalence is still low in the Netherlands. The second part of this thesis focuses on eradication and/or treatment of these micro-organisms with ‘fecal microbiota transplantation’ of healthy donor feces. It describes the establishment of the Netherlands Donor Feces Bank, and the research, experiences and successes of FMT in the treatment of patients with recurrent C. difficile infections and MDRO. The experience of this thesis may help the establishment, utilization, standardization and maturation of stool banks and research institutes of the next-generation of microbiota modifying therapies.