Microbial and antimicrobial resistance signatures differentiate healthy and inflamed ileal pouches in patients with ulcerative colitis.
4 affiliations
- 1Center for Microbial Communities, Department of Chemistry & Bioscience, Aalborg University, Aalborg, Denmark.
- 2Department of Gastrointestinal Surgery, Aalborg University Hospital, Aalborg, Denmark.
- 3Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.
- 4Center for Molecular Prediction of Inflammatory Bowel Disease, PREDICT, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark.
Abstract
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. 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. 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. 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.
Related
- Gut microbiota, microbial metabolites, and mucosal barrier dysfunction in benign anorectal disorders and ulcerative colitis: shared mechanisms, clinical links, and precision interventions
- Profiling Systemic IgG-Targeted Gut Microbiota Reveals Disease Activity-Associated Bacterial Signatures in Ulcerative Colitis
- Commentary: Resistance breakers: a novel approach to tackle biofilm associated infections and antimicrobial resistance
- Intrinsic Disorder as a New Frontier in Antimicrobial Resistance and Bacterial Fitness
- Amira: detection of single and multi-copy antimicrobial resistance genes directly from long reads using gene-space de Bruijn graphs
BibTeX
@article{dall2026microbial,
title = {{Microbial and antimicrobial resistance signatures differentiate healthy and inflamed ileal pouches in patients with ulcerative colitis.}},
author = {Sebastian Mølvang Dall and Alberte Holm Møllekær and Sabrina Just Kousgaard and Sarah Søgaard Jakobsen and Lone Larsen and Bertil Sørensen and Ole Thorlacius-Ussing and Mads Albertsen},
journal = {Journal of Crohn's \& colitis},
year = {2026},
month = nov,
doi = {10.1093/ecco-jcc/jjag150},
url = {https://europepmc.org/article/MED/42998368},
note = {CC BY},
}
RIS
TY - JOUR
TI - Microbial and antimicrobial resistance signatures differentiate healthy and inflamed ileal pouches in patients with ulcerative colitis.
AU - Sebastian Mølvang Dall
AU - Alberte Holm Møllekær
AU - Sabrina Just Kousgaard
AU - Sarah Søgaard Jakobsen
AU - Lone Larsen
AU - Bertil Sørensen
AU - Ole Thorlacius-Ussing
AU - Mads Albertsen
PY - 2026
DA - 2026/11/01
JO - Journal of Crohn's & colitis
DO - 10.1093/ecco-jcc/jjag150
UR - https://europepmc.org/article/MED/42998368
AB - 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. 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. 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. 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.
SN - 1873-9946
SN - 1876-4479
ER -