BACKGROUND: Faecal microbiota transplantation (FMT) is an effective treatment for patients with recurrent Clostridioides difficile infection, but donor selection can influence its clinical success. We aimed to investigate the effect of clinical donor characteristics on FMT outcomes in patients with C difficile infection. METHODS: In this single-centre, prospective cohort study, we included all donors who fulfilled the national criteria for faeces donation and delivered donations to the Centre for Faecal Microbiota Transplantation, Aarhus University Hospital, Denmark, between May 2, 2016, and Oct 31, 2023, and corresponding recipients treated with one-dose FMT for primary or recurrent C difficile infection. In mixed-effects models, we evaluated the effect of donor sex, age, BMI, smoking status, donation stool consistency, total donation weight, antibiotic use, Helicobacter pylori carriage, birth mode, donor-recipient sex concordance, and the alpha diversity of faeces donations on FMT outcomes in recipients. The primary outcome was the resolution of diarrhoea associated with C difficile infection in patients 8 weeks after FMT. FINDINGS: Among 145 blood donors who also donated faeces, 115 (79·3%) were men and 30 (20·7%) were women. 90 (62·1%) provided faeces for 1351 evaluable FMTs in 952 patients with C difficile infection. 1037 (76·8%) FMTs were administered through oral capsules, 151 (11·2%) via colonoscopy, and 163 FMTs (12·1%) via nasojejunal tube. Antibiotic use 3-12 months before donation decreased the effectiveness of FMT (odds ratio 0·55 [95% CI 0·33-0·91]
p=0·019). Compared with donations with a Bristol Stool Form Scale (BSFS) score of 3, donations with a score of 4 (odds ratio 1·38 [95% CI 1·04-1·83]
p=0·024) and 5 or above (2·89 [1·33-6·26]
p=0·0072) showed improved FMT effectiveness. Donor sex, BMI, smoking status, H pylori carriage, birth mode, total donation weight, and donor-recipient sex concordance did not affect FMT outcomes. INTERPRETATION: Expanding current donor selection criteria to avoid antibiotic use in the 12 months preceding donation and including donations with a BSFS score of 5 might improve FMT outcomes for patients with C difficile infection. Our findings call for the revision of current clinical donor screening practices, and future studies could further optimise the criteria for selecting optimal faeces donors. FUNDING: Innovation Fund Denmark.