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BACKGROUND & AIMS: Patients with multiple recurrent Clostridioides difficile infection (rCDI) have a disturbed gut microbiota that can be restored by fecal microbiota trans-plantation (FMT). Despite extensive screening, healthy feces donors may carry bacteria in their intestinal tract that could have long-term health effects, such as potentially procarci-nogenic polyketide synthase-positive (pks+) Escherichia coli. Here, we aim to determine whether the pks abundance and persistence of pks+ E coli is influenced by pks status of the donor feces. METHODS: In a cohort of 49 patients with rCDI treated with FMT and matching donor samples-the largest cohort of its kind, to our knowledge-we retrospectively screened fecal metagenomes for pks+ E coli and compared the presence of pks in patients before and after treatment and to their respective donors. RESULTS: The pks island was more prevalent (P = .026) and abundant (P < .001) in patients with rCDI (pre-FMT, 27 of 49 [55%]; median, 0.46 reads per kilobase per million [RPKM] pks) than in healthy donors (3 of 8 donors [37.5%], 11 of 38 samples [29%]; median, 0.01 RPKM pks). The pks status of patients post-FMT depended on the pks status of the donor suspension with which the patient was treated (P = .046). Particularly, persistence (8 of 9 cases) or clearance (13 of 18) of pks+ E coli in pks+ patients was correlated to pks in the donor (P = .004). CONCLUSIONS: We conclude that FMT contrib-utes to pks+ E coli persistence or eradication in patients with rCDI but that donor-to-patient transmission of pks+ E coli is unlikely.

Gut colonization with multi-drug resistant organisms (MDROs) or enteropathogenic bacteria such as Clostridioides difficile can precede development of an infection and is considered an important public health concern. The gut microbiome is able to confer resistance against colonization and infection of such bacteria and this capability is termed colonization resistance. The aims of this thesis are 1) to recognize and identify bacteria or bacterial communities providing colonization resistance against enteropathogenic microorganisms and antibiotic resistant bacteria, and 2) to contribute to the microbiome research field by developing and applying new technical approaches. This thesis has been divided into three parts. First, current knowledge of microbiome-mediated colonization resistance against enteropathogens is summarized and supplemented with an overview of opportunities and challenges in development of new microbiome-based therapeutics. The second part of this thesis focuses on method optimization for microbiome research, both for wet-lab and dry-lab procedures. The final part describes changes in the human gut microbiota during infection or colonization by potentially pathogenic enteropathogens, including hookworm, C. difficile and MDROs.