Long-Term Outcomes After CDI: FMT Versus Antibiotic-Only Treatment

Study design and setting This is a single-center, long-term observational cohort study conducted at the Department of Infectious Diseases, Umeå University Hospital, Sweden. The study enrolls adult patients treated for CDI between February 1, 2016 and December 31, 2024, providing up to 10 years of follow-up from the index CDI episode. Participants are stratified into two groups: FMT-treated and antibiotic-only treated.

CDI case definition Compatible clinical presentation (≥3 loose stools in 24 hours) plus a positive nucleic acid amplification test (LAMP) for C. difficile, consistent with ESCMID diagnostic criteria.

Recruitment Potentially eligible living subjects are identified from departmental diagnosis records and contacted by mail with written study information and an opt-out form. Those who do not return the opt-out form are contacted by telephone and invited to a single study visit for informed consent and enrollment. Deceased individuals are included in safety analyses only, without contact with next of kin.

Biological sampling Blood: EDTA plasma, serum, PBMC isolation Fecal sample Urine sample Nasopharyngeal swab

Archived donor fecal samples and pre- and post-FMT patient samples from the Umeå FMT biobank will be retrieved for longitudinal comparisons.

Observational measures Gut and nasopharyngeal microbiota will be characterized by shotgun metagenomics (strain-level resolution) and 16S rRNA sequencing. Resistome profiling and detection of multidrug-resistant organisms by culture will be performed on fecal samples. Global and targeted metabolomics (short-chain fatty acids, bile acids, redox metabolites) will be performed on feces, urine, and blood. Gut barrier markers in blood will include LPS, LPS-binding protein (LBP), and EndoCAb. Systemic immune profiling will include cytokine panels, soluble immune mediators, antibodies, and transcriptomic profiling of peripheral blood mononuclear cells. The host genome will not be sequenced. Clinical observational measures will include additional CDI after index CDI. Pharmacological treatments and comorbidity at index CDI and follow-up, as well as any antibiotic exposure during follow-up will be collected from the medical records.

• Donor gut microbiota long-term engraftment [Срок оценки: At follow-up visit 1-10 years after baseline CDI]
• Stool short-chain fatty acid concentrations [Срок оценки: At follow-up visit 1-10 years after baseline CDI]
• Circulating markers of intestinal barrier function [Срок оценки: At follow-up visit 1-10 years after baseline CDI]
• Health-related quality of life [Срок оценки: At follow-up visit 1-10 years after baseline CDI]
• Number of participants with new Clostridioides difficile infection episodes after subsequent antibiotic exposure [Срок оценки: Within 1-10 years after baseline CDI]
• Incidence of new comorbidities after FMT versus antibiotic-only treatment [Срок оценки: From baseline CDI to 1-10 year follow-up or prior death]