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The gut microbiome has been implicated in a range of diseases and there is a rapidly growing understanding of this ecosystem's importance in inflammatory bowel disease. We are yet to identify a single microbe that causes either ulcerative colitis (UC) or pouchitis, however, reduced microbiome diversity is increasingly recognised in active UC. Manipulating the gut microbiome through dietary interventions, prebiotic and probiotic compounds and faecal microbiota transplantation may expand the therapeutic landscape in UC. Specific diets, such as the Mediterranean diet or diet rich in omega-3 fatty acids, may reduce intestinal inflammation or potentially reduce the risk of incident UC. This review summarises our knowledge of gut microbiome therapies in UC and pouchitis.

Background: Restorative proctocolectomy with ileal pouch-anal anastomosis is considered the procedure of choice in patients with ulcerative colitis refractory to medical therapy. Subsequent inflammation of the pouch is a common complication and in some cases, pouchitis fails to respond to antibiotics, the mainstay of treatment. In such cases, corticosteroids, immunomodulatory or biologic treatments are options. However, our understanding of the efficacy of anti-tumour necrosis factor medications in both chronic pouchitis and Crohn's-like inflammation is based on studies that include relatively small numbers of patients., Methods: This was an observational, retrospective, multi-centre study to assess the long-term effectiveness and safety of infliximab (IFX) for inflammatory disorders related to the ileoanal pouch. The primary outcome was the development of IFX failure defined by early failure to IFX or secondary loss of response to IFX., Results: Thirty-four patients met the inclusion criteria; 18/34 (53%) who were initiated on IFX for inflammatory disorders of the pouch had IFX failure, 3/34 (8%) had early failure and 15/34 (44%) had secondary loss of response with a median follow-up of 280 days (range 3-47 months). In total, 24/34 (71%) avoided an ileostomy by switching to other medical therapies at a median follow-up of 366 days (1-130 months)., Conclusions: Initial IFX therapy for pouch inflammatory conditions is associated with IFX failure in just over half of all patients. Despite a high failure rate, an ileostomy can be avoided in almost three-quarters of patients at four years by using other medical therapies.

Background: Restorative proctocolectomy is the procedure of choice in patients with ulcerative colitis refractory to medical therapy. Prepouch ileitis is characterized by mucosal inflammation immediately proximal to the pouch. Prepouch ileitis is uncommon, and long-term follow-up data are lacking., Objective: The aim of this study is to report the long-term outcomes of prepouch ileitis., Design: We followed up a cohort of patients with prepouch ileitis that was originally described in 2009. Patients were followed up until the last recorded clinic attendance or at the point of pouch failure. Follow-up data collected included stool frequency, endoscopic findings, treatment, and overall pouch function., Setting: We accessed a prospectively maintained database at our institution between January 2009 and January 2017., Patients: Three of the 34 patients originally described in 2009 were lost to follow-up; we reanalyzed data on the remaining 31., Main Outcome Measure: The rate of pouch failure was defined as the need for ileostomy or pouch revision., Results: All 31 patients had coexisting pouchitis at index diagnosis of prepouch ileitis. The median length of follow-up from the index pouchoscopy was 98 (range, 27-143) months. Seven (23%) patients who had an index pouchoscopy with prepouch ileitis went on to pouch failure, which is significantly higher than expected (p = 0.03). Five (71%) of these patients had chronic pouchitis, and 2 (29%) had small-bowel obstruction due to prepouch stricture. Two patients had evidence that would support possible Crohn's disease at long-term follow-up., Limitations: This was a retrospective analysis. Because of the nature of the study, there was some missing information that may have influenced the results. Our study is further limited by small patient numbers., Conclusions: Prepouch ileitis is associated with a significantly increased risk of pouch failure compared with the overall reported literature for restorative proctocolectomy. Prepouch ileitis does not appear to be strongly predictive of Crohn's disease at long-term follow-up. See Video Abstract at http://links.lww.com/DCR/A480.

Background: The resident gut microbiota is essential for physiological processes; the disturbance of its balance is linked to intestinal inflammation. The ileoanal pouch is a model for the study of intestinal inflammation, as inflammation of the pouch is common and mostly develops within 12 months following ileostomy closure. This allows the longitudinal study of the microbiota, giving insight into the microbiota changes during transition from a normal to an inflamed pouch., Aim: To explore the literature on the microbiota of the ileoanal pouch in health and disease., Methods: A systematic computer search of the on-line bibliographic databases MEDLINE and EMBASE was performed between 1966 and February 2017. Randomised controlled trials, cohort studies and observational studies were included. Studies were included if they reported microbiota analysis on faecal samples or tissue from the ileoanal pouch., Results: Twenty-six papers were eligible. Following ileostomy closure, anaerobic bacteria are the abundant species in the ileoanal pouch with presence of a diverse microbiota key to maintaining a healthy ileoanal pouch. Acute pouchitis is associated with an increase in Clostridia species, while chronic pouchitis is associated with an increase in Staphylococcus aureus. In the treatment of pouchitis, a decrease in Clostridia species appears to be associated with treatment response., Conclusion: The microbiota plays an important role in both the inflamed and the healthy ileoanal pouch. A direct causal relationship between individual microbiota changes and inflammation has not yet been established, but manipulation of the ileoanal pouch microbiota may be a novel therapeutic avenue to explore., (© 2017 John Wiley & Sons Ltd.)

Aim: Chronic peri-pouch sepsis (CPPS) may be mistaken for antibiotic-dependent or refractory primary idiopathic pouchitis (ADRP), but requires different treatment such as drainage. The study aimed to identify the prevalence of CPPS in patients thought to have ADRP. The secondary aims were to identify any specific features on pouchoscopy suggesting CPPS and to determine the results of treatment for CPPS., Method: The records of patients who had been treated for ADRP between March 2006 and June 2015 were reviewed retrospectively. Only those with endoscopic evidence of pouch inflammation who had also undergone MRI of the pelvis were included. The findings on pouchoscopy and the outcome of treatment were determined., Results: Sixty-eight patients (43 men, 63%) were identified with apparent ADRP between March 2006 and June 2015. MRI of the pelvis showed CPPS in 26 (38%). In those with CPPS, the inflammation was more often located in the upper pouch alone (15%) compared with patients without CPPS (0%) (P = 0.0184). Examination under anaesthesia was performed in 13 of those with CPPS. In five a collection was identified and drained; symptoms improved in only one (4%). Eighteen patients (69%) remained on antibiotics and seven (27%) had a defunctioning stoma or underwent pouch excision., Conclusion: In patients thought to have ADRP, 38% had CPPS on MRI. There was no clinically relevant specific feature on pouchoscopy suggestive of CPPS. The possibility of CPPS should be considered early in patients with apparent ADRP and pelvic MRI performed. This might lead to earlier detection of CPPS and appropriate treatment., (Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.)

Background: Restorative proctocolectomy with ileal pouch anal anastomosis (IPAA) is considered the procedure of choice in patients with ulcerative colitis (UC) refractory to medical therapy. The incidence of pouchitis is 40% at 5 years. Ten to 15% of patients with pouchitis experience chronic pouchitis., Aim: To determine the efficacy of medical therapies for the treatment of chronic refractory pouchitis in patients undergoing IPAA for UC., Methods: A systematic computer-assisted search of the on-line bibliographic database MEDLINE and EMBASE was performed between 1966 and February 2016. All original studies reporting remission rates following medical treatment for chronic pouchitis were included. All study designs were considered. Remission was defined according to the individual study. Remission endpoints ranged from 15 days to 10 weeks. Chronic pouchitis was defined by each study., Results: Twenty-one papers were considered eligible. Results from all studies combined suggested that overall remission was obtained in 59% of patients (95% CI: 44-73%). Antibiotics significantly induced remission in patients with chronic pouchitis with 74% remission rate (95% CI:56-93%), (P < 0.001). Biologics significantly induced remission in patients with chronic pouchitis with 53% remission rate (95% CI:30-76%), (P < 0.001). Steroids, bismuth, elemental diet and tacrolimus all can induce remission but failed to achieve significance. Faecal microbiota transplantation in a single study was not found to achieve remission., Conclusions: Treatment of chronic refractory pouchitis remains difficult and is largely empirical. Larger randomised controlled trials will help aid the management of chronic pouchitis., (© 2016 John Wiley & Sons Ltd.)

Inflammatory bowel diseases are characterised by inflammation that compromises the integrity of the epithelial barrier. The intestinal epithelium is not only a static barrier but has evolved complex mechanisms to control and regulate bacterial interactions with the mucosal surface. Apical tight junction proteins are critical in the maintenance of epithelial barrier function and control of paracellular permeability. The characterisation of alterations in tight junction proteins as key players in epithelial barrier function in inflammatory bowel diseases is rapidly enhancing our understanding of critical mechanisms in disease pathogenesis as well as novel therapeutic opportunities. Here we give an overview of recent literature focusing on the role of tight junction proteins, in particular claudins, in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer.

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.

Background: Tight junction proteins (TJPs) and dendritic cells (DC) are critical in the pathogenesis of inflammatory bowel diseases. The ileal pouch formed by restorative proctocolectomy provides a unique human model for studying the pathogenesis of inflammatory bowel diseases. Data implicate the microbiota in the pathogenesis of pouchitis, while the role of innate immune factors remains unclear. We performed longitudinal and cross-sectional studies of patients after restorative proctocolectomy and assessed TJP and DC characteristics in the ileal pouch., Methods: Mucosal biopsies were taken from the ileal pouch of patients with ulcerative colitis (UC) and familial adenomatous polyposis (n = 8). Of patients with UC, one group (n = 5) was followed longitudinally over the first year after ileostomy closure, another group had pouchitis (n = 15), and another group no inflammation (n = 18). Dendritic cell phenotype and epithelial cell TJP expression were assessed using flow cytometric analysis., Results: Increased epithelial expression of the "pore-forming" TJP claudin 2, and DC expression of gut-homing markers CCR 9 and integrin β7, occurred early after ileostomy closure. In patients with UC with pouchitis, epithelial expression of ZO-1 and claudin 1 were reduced, DC were activated with increased CD40, and Toll-like receptor 4 expression increased. In pouchitis, DC expressing CCR 9 were decreased, whereas DC expressing β7 increased., Conclusions: Abnormalities were found in TJP expression in the pouch of patients with UC, in particular, increased expression of the pore-forming claudin 2 as an early event in the development of pouch inflammation and an aberrant DC phenotype was characterized in the ileal pouch of patients with UC.

Restorative proctocolectomy with ileal-pouch anal anastomosis (RPC) is the operation of choice for ulcerative colitis (UC) patients requiring surgery. It is also used for patients with familial adenomatous polyposis (FAP). Pouchitis accounts for 10% of pouch failures. It is an idiopathic inflammatory condition that may occur in up to 50% of patients after RPC for UC. It is rarely seen in FAP patients after RPC. The etiology of pouchitis remains unclear. An overlap with UC is suggested by the frequency with which pouchitis affects patients with UC compared with FAP patients. There is significant clinical evidence implicating bacteria in the pathogenesis of pouchitis. Studies using culture and molecular methods demonstrate a dysbiosis of the pouch microbiota in pouchitis. Risk factors, genetic associations, and serological markers of pouchitis suggest that the interactions between the host immune responses and the pouch microbiota underlie the etiology of this idiopathic inflammatory condition. Here we present a detailed review of the data focusing on the pouch microbiota and the immune responses that support this hypothesis. We also discuss the contribution of luminal metabolic factors and the epithelial membrane in the etiology of this inflammatory process. The ileoanal pouch offers a unique opportunity to study the inter-relationships between the gut microbiota and host immune responses from before the onset of disease. For this reason the study of pouchitis could serve as a human model that significantly enhances our understanding of inflammatory bowel diseases in general., (Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.)

Jonathan P Segal,1,2 Matteo Rottoli,3 Richard K Felwick,4 Guy HT Worley,1,2 Simon D McLaughlin,4 Carlo Vallicelli,3 Paul Bassett,5 Omar D Faiz,1,2 Ailsa L Hart,1,2 Susan K Clark1,2 1Inflammatory Bowel Disease Department, St Mark’s Hospital, Harrow, UK; 2Department of Surgery and Cancer, Imperial College, London, UK; 3Surgery of the Alimentary Tract, Sant’Orsola – Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy; 4Department of Gastroenterology, The Royal Bournemouth and Christchurch Hospitals, Bournemouth, UK; 5Statsconsultancy Ltd, Amersham, UK Aim: Prepouch ileitis (PPI) is inflammation of the ileum proximal to an ileoanal pouch, usually associated with pouchitis. The treatment of PPI as a specific entity has been poorly studied, but it is generally treated concurrently with pouchitis. This to our knowledge is the largest study to explore the efficacy of biologics for the specific treatment of PPI.Methods: This was a retrospective observational study reporting outcomes following biological treatment in patients with PPI across three centers. Data were collected between January 2004 and February 2018 from two centers in the UK and one center in Italy. Outcomes included the continued presence of PPI following biologic therapy, pouch failure defined by the need for an ileostomy, and remission of PPI defined by the absence of any prepouch inflammation on endoscopic assessment within a year of biologic therapy.Results: There were 29 patients in our cohort. On last endoscopic follow-up, 20/29 still had endoscopic evidence of PPI, seven had achieved endoscopic remission and avoided an ileostomy, and two had no endoscopic follow-up. In our cohort 11 patients had an ileostomy after a median time from starting a biologic of 25 months (range 14–91).Conclusion: Biologics fail to induce endoscopic remission of PPI in the majority of patients. Just under one-third patients with PPI coexistent with pouchitis can achieve endoscopic remission with biologics. In a large proportion of patients with PPI, surgery may be required despite biologic use. Keywords: pouch, biologics, prepouch ileitis, pouchitis, restorative proctocolectomy, infliximab