Work

Microbial and antimicrobial resistance signatures differentiate healthy and inflamed ileal pouches in patients with ulcerative colitis

Year: 2026

Type: article

Abstract: BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) from healthy donors with a normally functioning colon has limited clinical effect in the treatment of chronic pouchitis. However, a normally functioning ileal pouch-anal anastomosis (IPAA) physiology differs from individuals with a healthy intact colon. We aimed to investigate the microbial characteristics of patients with a normally functioning IPAA (HealthyPouch) compared with chronic pouchitis (SickPouch), ulcerative colitis (UC), and a healthy intact colon microbiome (NormalGut). Furthermore, we investigated how repeated antibiotic use influences antimicrobial resistance on a bacterial genome level. METHODS: Fecal samples from 190 participants were collected; HealthyPouch (n = 38), SickPouch (n = 37), UC (n = 23), and NormalGut (n = 92) and sequenced with Illumina and taxonomically profiled. Samples from HealthyPouch, SickPouch, and NormalGut were also long-read sequenced using Oxford Nanopore Technologies for reconstruction of 12 282 metagenome-assembled genomes (MAGs). DNA methylation motifs were used for plasmid-host association. RESULTS: The HealthyPouch microbiome is distinct from both the UC, NormalGut, and SickPouch microbiome. Escherichia coli MAGs in the SickPouch (n = 21) microbiome had significantly higher co-occurring ciprofloxacin resistance mutations in the gyrA and parC genes, compared to both HealthyPouch (n = 26; BH adjusted P < .05) and NormalGut (n = 40; BH adjusted P < .05). Based on DNA methylation pattern, three plasmids were associated with E. coli carrying extended-spectrum beta lactamase genes. CONCLUSIONS: HealthyPouch microbiota differs from NormalGut microbiota, and could therefore be more appropriate for FMT treatment of chronic pouchitis. The association between E. coli and resistance gene-carrying plasmids underscores the importance of integrating plasmid analysis into metagenome-based approaches for personalized antibiotic treatment and resistance monitoring.

Source: Journal of Crohn s and Colitis

DOI: 10.1093/ecco-jcc/jjag150