Fecal microbiota transplantation for the decolonization of mucosal adherent-invasive Escherichia coli in Crohn's disease: an open-label pilot study.

Adherent-invasive Escherichia coli (AIEC) is implicated in Crohn's disease (CD) pathogenesis, but whether fecal microbiota transplantation (FMT) clears mucosal AIEC and alters fecal and mucosal microbiomes has not been studied. In this open-label pilot study, thirty adults with CD and seropositivity for serum anti-E.coli antibody (AEcAb) received a single colonoscopic FMT from one of two donors (ClinicalTrials.gov identifier NCT05611866). The primary outcome was adverse events (AEs) within 12 weeks after FMT; secondary outcomes included changes in mucosal AIEC, clinical measures, and fecal and mucosal microbiome profiles. Shotgun metagenomic sequencing for fecal samples and 16S rRNA sequencing for ileal mucosal samples were performed at baseline and after FMT. Baseline AEcAb levels were higher in patients with mucosal AIEC colonization (p = 0.019) and remained elevated after FMT. No FMT-related serious adverse events were reported. FMT was associated with mucosal AIEC decolonization in all 8 evaluable baseline-positive patients. Mucosal alpha diversity increased after FMT (p = 0.023), which correlated with reduced fecal calprotectin (p = 0.034). Microbial pathway profiles in CD patients resembled those of their respective donors with reduced donor-recipient dissimilarity post-FMT (p = 0.030), particularly among recipients with mucosal AIEC decolonization (p = 0.039). In conclusion, this open-label pilot study demonstrates the feasibility of FMT for modulating mucosal AIEC colonization in CD and highlights the importance of capturing microbial changes at the disease site that may be undetectable in fecal samples.