Introduction

Chronic pouchitis is a common complication following ileal pouch-anal anastomosis (IPAA), with limited effective treatment options.¹ Antibiotics remain the first-line therapy; however, in cases of chronic pouchitis, prolonged antibiotic use contributes to increased antimicrobial resistance within the ileal pouch microbiome.² Fecal microbiota transplantation (FMT) has been proposed as a means of restoring microbial balance. Nevertheless, randomized placebo-controlled trials have demonstrated that, although FMT can alter the microbiome, it does not confer clinical benefits compared to placebo.^3–5

Aims & Methods

Given the lack of efficacy of FMT using stool from healthy donors, the present study aims to characterize the microbiome of a healthy ileal pouch and to evaluate the impact of high antibiotic exposure in patients with chronic pouchitis.
In this cohort study, stool samples were collected from four groups: patients with a normally functioning IPAA, patients with chronic pouchitis, patients with ulcerative colitis, and healthy controls. Microbiome composition and antibiotic resistance genes were analyzed across these groups. Fecal samples underwent metagenomic sequencing, and metagenome-assembled genomes (MAGs) were reconstructed. For Escherichia coli MAGs, the antibiotic resistance gene (ARG) profiles and plasmid content were specifically examined.

Results

This study included 197 participants. A clear pattern emerged in the microbial composition, revealing that reduced alpha diversity is directly associated with declining gut function and clinical health. Both species richness and Shannon diversity were lowest in patients with chronic pouchitis and highest in healthy individuals, with intermediate levels observed in the other groups. Notably, the ileal pouch microbiome of many chronic pouchitis patients was dominated by E. coli. Given the potential clinical implications of high E. coli abundance, we further investigated the ARG profiles and plasmid content of E. coli MAGs. E. coli MAGs from chronic pouchitis patients exhibited a significantly higher frequency of single nucleotide polymorphisms (SNPs) associated with resistance to fluoroquinolones—an antibiotic uniformly used among this patient group—compared to MAGs from the normally functioning IPAA and healthy control cohorts. Furthermore, E. coli MAGs from chronic pouchitis patients harbored a greater number of plasmids, with an increased presence of plasmid-borne ARGs conferring resistance to antibiotics commonly administered in this group, relative to the other cohorts.

Conclusion

These findings demonstrate that the composition of the ileal pouch microbiome—both in chronic pouchitis and normally functioning IPAA—differs significantly from that of individuals with normal gut physiology. This suggests that the microbiome of a normally functioning IPAA may serve as a more appropriate baseline for comparative studies than the healthy gut microbiome. Additionally, our results indicate that antibiotic use exerts increased selective pressure on E. coli strains carrying antibiotic resistance genes, directly correlating with the types of antibiotics administered.

References

1. Hata K, Ishihara S, Nozawa H, et al. Pouchitis after ileal pouch-anal anastomosis in ulcerative colitis: Diagnosis, management, risk factors, and incidence. Dig Endosc 2017;29:26–34.
2. Shen B, Kochhar GS, Rubin DT, et al. Treatment of pouchitis, Crohn’s disease, cuffitis, and other inflammatory disorders of the pouch: consensus guidelines from the International Ileal Pouch Consortium. Lancet Gastroenterol Hepatol 2021;7:69–95.
3. Herfarth H, Barnes EL, Long MD, et al. Combined Endoscopic and Oral Fecal Microbiota Transplantation in Patients with Antibiotic-Dependent Pouchitis: Low Clinical Efficacy due to Low Donor Microbial Engraftment. Inflamm Intest Dis 2019;4:1–6.
4. Karjalainen EK, Renkonen-Sinisalo L, Satokari R, et al. Fecal Microbiota Transplantation in Chronic Pouchitis: A Randomized, Parallel, Double-Blinded Clinical Trial. Inflamm Bowel Dis 2021;27:1766–1772.
5. Kousgaard SJ, Cold F, Halkjær SI, et al. The effect of non-pooled multi-donor faecal microbiota transplantation for inducing clinical remission in patients with chronic pouchitis: Results from a multicentre randomised double-blinded placebo-controlled trial (MicroPouch). J Crohn’s Colitis 2024;18:1753–1766.

Introduction

Pathological esophageal acid exposure may persist in patients with Barrett’s esophagus (BE) despite standard proton pump inhibitor (PPI) therapy and symptom control, although current guidelines recommend at least standard-dose PPI for all patients with BE.¹

Aims & Methods

Aim was to evaluate the role of esophageal function testing in assessing acid exposure in BE patients on PPI therapy and in predicting neoplastic progression. We conducted a multicenter retrospective study including asymptomatic BE patients (defined by GerdQ total score <8 and a score of 0 on the first GerdQ item) who underwent high-resolution manometry and 24-hour pH impedance monitoring while on various PPI regimens. Maximal PPI therapy included esomeprazole 40 mg, pantoprazole 40 mg, rabeprazole 20 mg, or lansoprazole 30 mg, all administered twice daily. All other regimens were considered standard dosing. Index upper endoscopy with biopsies was performed under the same therapeutic regimen. Histologically, presence and degree of neoplasia (all confirmed by a second pathologist) was recorded. Acid exposure time (AET) <4% was defined as adequate acid control; AET >6% as pathological reflux. Predictors of pathological reflux and neoplasia were assessed using logistic regression analysis.

Results

A total of 135 patients (2016-2025) were included (mean age 58 ± 15 years; 73% male). Median BE length was C1 (range 0–3 cm) and M2 (range 1–5 cm), with 41% (n=56) classified as having long-segment BE. Sixty-seven patients (50%) were on standard-dose PPI. Pathological reflux was identified in 37 patients (27%), of whom 25 (67%) were on standard-dose therapy. Fourteen patients (10%) had borderline AET values (4–6%). Among the 84 patients (62%) with adequate acid control, 33 (39%) were taking standard-dose PPI. On multivariable analysis, standard-dose PPI (OR 3.04; 95% CI 1.34–6.89; p=0.008) and type III esophagogastric junction morphology (OR 2.52; 95% CI 1.01–5.01; p=0.047), consistent with manometric hiatal hernia, were independently associated with pathological reflux. Non-dysplastic BE was found in 112 patients, while 13 (10%) had neoplasia at index endoscopy (8 low-grade dysplasia, 3 high-grade dysplasia, 2 intramucosal adenocarcinoma). Pathological reflux was the only independent predictor of neoplasia (OR 10.41; 95% CI 2.65–41.26; p<0.001).

Table 1. Logistic regression analysis for factors associated with neoplasia on index endoscopy.

Conclusion

Nearly one-third of asymptomatic BE patients exhibit pathological reflux on pH-monitoring despite PPI treatment, predominantly among those on standard-dose and with manometric hiatal hernia. Nonetheless, adequate acid control is achieved in over one-third of patients on standard PPI therapy. Pathological reflux is associated with a 10-fold increased risk of neoplasia.

References

1. Shaheen NJ, Falk GW, Iyer PG, et al. Diagnosis and Management of Barrett's Esophagus: An Updated ACG Guideline. Am J Gastroenterol. 2022;117(4):559-587.

Introduction

Pregnancy is common in women with inflammatory bowel disease (IBD), a population in whom optimal obstetric management is essential to ensure maternal and neonatal well-being. Vaginal delivery is generally recommended as the preferred mode of birth due to its lower risk of complications and faster recovery. Unnecessary caesarean section (C-section) delivery increases the risk of maternal complications, such as infection and thrombosis, and may negatively impact neonatal outcomes, including respiratory distress and delayed breastfeeding. Identifying the precise prevalence of C-sections and the factors driving that prevalence in women with IBD is essential to improve care and promote safe, evidence-based delivery planning.

Aims & Methods

To assess the frequency of C-section, and to identify factors associated with the mode of delivery in pregnant women with IBD included in the DUMBO registry.
Patients from DUMBO registry, a prospective multicentre cohort study of pregnant women with IBD in Spain, were included. The registry systematically collects demographic characteristics, obstetric history, IBD phenotype and activity, treatments received during pregnancy, and pregnancy-related complications. Mode of delivery is recorded for all participants. In cases of C-section, investigators document whether the indication was obstetric or IBD-related, as well as the specific reason for the procedure. Logistic regression analysis was performed to identify clinical and disease-related variables independently associated with the likelihood of C-section.

Results

A total of 1,012 women had given birth at the time of data analysis; mean age 34 years (standard deviation 4.8); median IBD duration 8.8 years (interquartile range 4.5–13); 626 (57%) had Crohn’s disease (CD) (21% had perianal disease, 19% active), 216 (19%) had previous surgery due to IBD, 464 (42%) were exposed to biologics, and 122 (11%) had active disease during pregnancy. A total of 293 deliveries (29%) were by C-section. Among C-sections, 237 (81%) were indicated for obstetric reasons, and 56 (19%) for IBD. In univariate analysis, older maternal age, longer IBD duration, to have CD (vs. ulcerative colitis), prior IBD surgery, active perianal disease, and exposure to biologic therapy during pregnancy were significantly more frequent among patients undergoing C-section compared to those with vaginal delivery (table 1). In the multivariate analysis, older maternal age [Odds ratio (OR) = 1.05, 95% confidence interval (CI) = 1.02–1.08], biologic treatment during pregnancy (OR = 1.46, 95%CI 1.08–1.95), prior IBD surgery (OR = 1.47, 95%CI 1.47–2.95), and active perianal disease (OR = 4.89, 95% CI 1.86–12.8) were independently associated with a higher risk of C-section.

Conclusion

One-third of deliveries in women with IBD are by C-section (a figure higher than that in general population¹). In 20% of cases, the indication for C-section was directly related to IBD-specific conditions. Several factors associated with an increased risk of C-section were identified, which are also recognized as predictors of more severe disease. Further efforts are needed to assess the appropriateness of C-section indications and to reduce unnecessary procedures in women with IBD.

References

¹ Ministerio de Sanidad. Annual report on the National Health System of Spain 2023 [Internet]. Madrid: Ministerio de Sanidad; 2023 [accessed 2025 April 14]. p. 86. Available from: https://www.sanidad.gob.es/estadEstudios/estadisticas/sisInfSanSNS/tablasEstadisticas/InfAnualSNS2023/INFORME_ANUAL_2023.pdf

Disclosure

María José Casanova María José Casanova, has received education or research funding from Pfizer, Takeda, Janssen, MSD, Dr. Falk, Shire, Ferring, Galápagos, Abbvie and Lilly.
María Chaparro has served as speaker, consultant or research or education funding from MSD, Abbvie, Hospira, Pfizer, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Biogen, Gilead and Lilly.
Javier P. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from MSD, Abbvie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers, Gilead/Galapagos, Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine and Vifor Pharma.
Cristina Calvino-Suarez, has served as a speaker for or has received research funding from MSD, AbbVie, Janssen, Takeda and Adacyte.
Pilar López Serrano has received grants from MSD, Abbvie, Takeda, Janssen, Faes, Ferring and Dr Falk Pharma.
Noemí Manceñido Marcos has served as a speaker and consultant for or received financial support for educational activities from Janssen, Abbvie, Pfizer, Takeda, Ferring, Faes Farma, Dr. Falk Pharma, and Tillots Pharma.
Marta Maia Boscá Watts Conflictos de interés: MSD, Ferring, Abbvie, Janssen, Biogen, Pfizer, Galápagos, Otsuka, Kern pharma y Takeda.
Agnès Fernández-Clotet has served as a speaker, or has recieves education funding from Dr. Falk, Janssen, Takeda, Chiesi and Pfizer.
Lara Arias García has served as speaker or has received research or education funding from MSD; Abbvie; Kern Pharma; Ferring; Faes Farma; Shire Pharmaceuticals; Pfizer; Takeda; Janssen; Tillots Pharma and OtsuKa Pharmaceutical.
Lucía Marquez-Mosquera has been served as speaker and / or has received research or education funds from Abbvie, Pfizer, Takeda, Janssen.
Marta Calvo Moya has served as a speaker, consultant and advisory member for or has received research funding from MSD, Abbvie, Takeda, Jannsen, Pfizer, Lilly, Mylan, Kern Pharma, Ferring, Shire Pharmaceuticals, Tillots, Dr. Falk Pharma, Chiesi, and Gebro Pharma.
Miriam Mañosa has served as a speaker, consultant and advisory member for or has received research funding from AbbVie, Janssen, MSD, Pfizer, Faes, Takeda, Tillots, Ferring.
Vicent Hernández has served as consultant, has served as speaker, has received travel support or research funding from MSD, AbbVie, Ferring, Dr. Falk Pharma, Tillotts Pharma, Pfizer, Takeda, Janssen, KernPharma Biologics, Adacyte, Sandoz, Biogen, Fresenius-Kabi, FAES Farma and Galapagos.
Raquel Camargo-Camero, He recibido financiación para diferentes tipos de actividades formativas de Janssen, Ferring, Abbvie, Falk, Pfizer, Galápagos y Takeda.
Iván Guerra has served as speaker or has received education funding from Takeda and Tillots.
David Busquets declares educational activities, research projects and scientific meetings sponsored by Abbvie, Janssen, Ferring, Pfizer, Tillots Pharma and Takeda.
Montserrat Rivero has served as a speaker or advisory member from TaKeda, Janssen, Galapagos, Ferring and Pfizer.
Iago Rodríguez-Lago has received financial support for traveling and educational activities from or has served as an advisory board member for Abbvie, Adacyte, Celltrion, Chiesi, Danone, Ferring, Faes Farma, Janssen, Galapagos, MSD, Pfizer, Roche, Takeda, and Tillotts Pharma. Financial support for research: Tillotts Pharma.
Rest of authors have nothing to declare.