Pouchitis

Faecal microbiota transplantation (FMT) is effective in the treatment of Clostridium difficile infection, where efficacy correlates with changes in microbiota diversity and composition. The effects of FMT on recipient microbiota in inflammatory bowel diseases (IBD) remain unclear. We assessed the effects of FMT on microbiota composition and function, mucosal immune response, and clinical outcome in patients with chronic pouchitis. Eight patients with chronic pouchitis (current PDAI ≥7) were treated with FMT via nasogastric administration. Clinical activity was assessed before and four weeks following FMT. Faecal coliform antibiotic sensitivities were analysed, and changes in pouch faecal and mucosal microbiota assessed by 16S rRNA gene pyrosequencing and (1)H NMR spectroscopy. Lamina propria dendritic cell phenotype and cytokine profiles were assessed by flow cytometric analysis and multiplex assay. Following FMT, there were variable shifts in faecal and mucosal microbiota composition and, in some patients, changes in proportional abundance of species suggestive of a "healthier" pouch microbiota. However, there were no significant FMT-induced metabolic or immunological changes, or beneficial clinical response. Given the lack of clinical response following FMT via a single nasogastric administration our results suggest that FMT/bacteriotherapy for pouchitis patients requires further optimisation.

BackgroundPouchitis is the most common long-term complication of in patients with restorative proctocolectomy and ileal pouch-anal anastomosis. Patients often develop antibiotic-dependent form of pouchitis requiring long-term antibiotic therapy for remission maintenance. Rifaximin, an oral, non-systemic, broad-spectrum antibiotic with a favorable safety profile, may be a promising candidate agent for maintenance therapy. This historical cohort open-label study investigated the efficacy and tolerability of rifaximin in maintaining symptomatic and endoscopic remission in patients with antibiotic-dependent pouchitis.MethodsAdult patients with antibiotic-dependent pouchitis received a 2-week course of various antibiotics for induction of remission. Patients in remission then began maintenance therapy with rifaximin 200 mg/day (to 1800 mg/day) for up to 24 months. Pouchitis Disease Activity Index symptom scores were assessed every 1-3 months to evaluate efficacy.ResultsFifty-one patients began maintenance therapy with rifaximin (median dose 200 mg/day); 33 (65%) maintained remission through 3 months (primary endpoint). Of these 33 patients, 26 (79%) successfully continued maintenance for 6 months after beginning maintenance, 19 (58%) successfully continued for 12 months, and two (6%) successfully continued for 24 months. Only one patient reported an adverse event (transient facial rash).ConclusionPatients' response to rifaximin as a maintenance therapy appears to be favorable in this open-labeled trial of antibiotic-dependent pouchitis. Randomized, placebo-controlled trials with a longer follow-up are warranted.

A 2-year longitudinal microbiome study of 22 patients who underwent colectomy with an ileal pouch anal anastomosis detected significant increases in distinct populations of Bacteroides during 9 of 11 patient visits that coincided with inflammation (pouchitis). Oligotyping and metagenomic short-read annotation identified Bacteroides populations that occurred in early samples, bloomed during inflammation, and reappeared after antibiotic treatment. Targeted cultivation of Bacteroides isolates from the same individual at multiple time points and from several patients detected subtle genomic changes, including the identification of rapidly evolving genomic elements that differentiate isogenic strains of Bacteroides fragilis from the mucosa versus lumen. Each patient harbored Bacteroides spp. that are closely related to commonly occurring clinical isolates, including Bacteroides ovatus, B. thetaiotaomicron, B. vulgatus, and B. fragilis, which contained unique loci in different patients for synthesis of capsular polysaccharides. The presence of unique Bacteroides capsular polysaccharide loci within different hosts and between the lumen and mucosa may represent adaptations to stimulate, suppress, and evade host-specific immune responses at different microsites of the ileal pouch.ImportanceThis longitudinal study provides an opportunity to describe shifts in the microbiomes of individual patients who suffer from ulcerative colitis (UC) prior to and following inflammation. Pouchitis serves as a model for UC with a predictable incidence of disease onset and enables prospective longitudinal investigations of UC etiology prior to inflammation. Because of insufficient criteria for predicting which patients will develop UC or pouchitis, the interpretation of cross-sectional study designs suffers from lack of information about the microbiome structure and host gene expression patterns that directly correlate with the onset of disease. Our unique longitudinal study design allows each patient to serve as their own control, providing information about the state of the microbiome and host prior to and during the course of disease. Of significance to the broader community, this study identifies microbial strains that may have genetic elements that trigger the onset of disease in susceptible hosts.

Background and aimsThe aim of this prospective single-center study is to train convolutional neural networks (CNNs) to detect the presence of pouchitis in two-dimensional (2D) images acquired during pouchoscopies and test its feasibility.MethodsTwo separate networks were constructed. The goal of network 1 was to detect whether an inflammation was present. Network 2 was designed to classify endoscopic findings of pouchitis, according to the pouchitis disease activity index (PDAI) score. The dataset was divided into three distinct sets: a training set, a validation set, and a test set. The performance was quantified using a tenfold cross-validation approach.ResultsFor the detection of inflammation, sensitivity was 71.78% with a specificity of 90.35%. When differentiating the six endoscopic findings according to the PDAI score, the sensitivity ranged from a low of 38% for the 'ulceration' class to a high of 67.18% for the 'friability' class, with a specifity of 94.12% ('ulceration') and 96.57% ('friability').ConclusionsThis study shows that an artificial, intelligence-based image recognition software can be trained to recognize the endoscopic features of pouchitis with reasonable accuracy. The results, although encouraging, confirm that artificial intelligence (AI) performance in this context remains below human expert level. A larger dataset, human benchmarking and more appropriate endoscopic markers are required to reach clinically relevant performance. Trial registration This trial was registered in the 'ClinicalTrials.gov' database on 26 April 2021 (NCT04864587).