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BACKGROUND: Pouchitis is the most frequent complication following restorative proctocolectomy and ileal pouch anal anastomosis (RP-IPAA) in patients with Ulcerative colitis (UC). Pediatric data on nutritional status during RP-IPAA and in patients with pouchitis are limited. AIMS: We aimed to delineate nutritional changes in children undergoing 2-stage and 3-stage surgeries and to evaluate the association between nutrition and the development of recurrent or chronic pouchitis. METHODS: This single-center retrospective study involved 46 children with UC who underwent a RP-IPAA. Data were collected at each surgical stage and for up to 2-year post-ileostomy takedown. We used Wilcoxon matched-pairs signed-rank test to evaluate the differences in nutritional markers across surgical stages and logistic regression to identify the factors associated with recurrent or chronic pouchitis. RESULTS: Twenty patients (43.5%) developed recurrent or chronic pouchitis. Children who underwent a 3-stage procedure had improvements in albumin, hematocrit, and body mass index (BMI)-for-age Z-scores (p < 0.01) between the first two stages. A positive trend in BMI-for-age Z-scores (p = 0.08) was identified in children with 2-stage procedures. All patients showed sustained nutritional improvement during the follow-up period. Among patients who underwent 3-stage surgeries, BMI worsened by 0.8 standard deviations (SDs) (p = 0.24) between the initial stages in those who developed recurrent or chronic pouchitis and improved by 1.1 SDs (p = 0.04) in those who did not. CONCLUSIONS: Early improvement in BMI-for-age Z-scores following the initial stage was associated with lower rates of recurrent or chronic pouchitis. Larger prospective studies are needed to validate these findings.

Inflammatory bowel disease (IBD) is a chronic condition that requires continuous medical treatment. To date, the medical management of patients with moderately-to-severely active IBD who develop dependence or resistance to corticosteroids is based on immunomodulator drugs. Such therapies are licenced after passing through three phases of randomized controlled trials (RCTs), and are subsequently adopted in clinical practice. However, the real-life population of IBD patients who require these therapies can significantly differ from those included in RCTs. As a matter of fact, there is a number of exclusion criteria – nearly ubiquitous in all RCTs – that prevent the enrolment of specific patients: Chronic refractory pouchitis or isolated proctitis in ulcerative colitis, short-bowel syndrome and stomas in Crohn’s disease, ileorectal anastomosis in both ulcerative colitis and Crohn’s disease, and elderly age are some representative examples. In this frontier article, we aim to give an overview of current literature on this topic, in order to address the main knowledge gaps that need to be filled in the upcoming years.

Low diversity intestinal dysbiosis has been associated with inflammatory bowel disease, including patients with ulcerative colitis with an ileo-anal pouch anastomosis. Furthermore, specific Escherichia coli phylogroups have been linked to inflammatory bowel disease. Our aim was to characterize the differences among microbiota and E. coli phylogroups in active and inactive pouchitis. Disease activity was assessed using the modified pouch disease activity index and by fecal calprotectin. Microbiota diversity was assessed by 16S rDNA MiSeq sequencing. E. coli phylogroup was determined after triplex PCR. Twenty patients with ulcerative colitis with an ileo-anal pouch anastomosis were included, 10 of whom had active pouchitis. Ileo-anal pouch anastomosis patients had an increased abundance of Proteobacteria colonization compared to patients with ulcerative colitis or Crohn’s disease and healthy controls, p = 1.4·10−5. No differences in E. coli phylogroup colonization could be determined between cases of active and inactive disease. No significant link was found between α-diversity and pouch inflammation. However, higher levels of Fusobacteria colonization were found in patients with a pouch with a fecal calprotectin level above 500, p = 0.02. In conclusion, patients with a pouch had an increased Proteobacteria abundance, but only Fusobacteria abundance was linked to inflammation.

The objective was to evaluate available literature on treatment of chronic pouchitis with fecal microbiota transplantation (FMT) focusing on clinical outcomes, safety, and different approaches to FMT preparation and delivery. A systematic review of electronic databases was conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials Library from inception through April 2020. Human studies of all study types reporting results of FMT to treat chronic pouchitis were included. Nine studies, reporting FMT treatment of 69 patients with chronic pouchitis were found eligible for the review. Most studies were case series and cohort studies rated as having fair to poor quality due to high risk of bias and small sample size. Only one randomized controlled trial was included, finding no beneficial effect of FMT. In total clinical response after FMT was reported in 14 (31.8%) out of 44 evaluated patients at various timepoints after FMT, and clinical remission in ten (22.7%) patients. Only minor self-limiting adverse events were reported. FMT varied greatly regarding preparation, length of treatment, and route of delivery. The effects of FMT on symptoms of chronic pouchitis are not established, though some studies show promising results. Future controlled well-designed studies are warranted.

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Author Posting. © The Author(s), 2016. This is the author's version of the work. It is posted here by permission of American Physiological Society for personal use, not for redistribution. The definitive version was published in American Journal of Physiology-Gastrointestinal and Liver Physiology 310 (2016): G973-G988, doi:10.1152/ajpgi.00017.2016., Gut dysbiosis, host genetics, and environmental triggers are implicated as causative factors in inflammatory bowel disease (IBD), yet mechanistic insights are lacking. Longitudinal analysis of ulcerative colitis patients following total colectomy with ileal anal anastomosis (IPAA) where >50% develop pouchitis, offers a unique setting to examine cause vs. effect. To recapitulate human IPAA, we employed a mouse model of surgically created blind self-filling (SFL) and self- emptying (SEL) ileal loops using wild-type (WT), IL-10 KO (IL10), and TLR4 KO (T4), and IL10/T4 double KO mice. After 5 weeks, loop histology, host gene/protein expression, and bacterial 16s rRNA profiles were examined. SFL exhibit fecal stasis due to directional motility oriented towards the loop end, whereas SEL remain empty. In wild type mice, SFL, but not SEL, develop pouch-like microbial communities without accompanying active inflammation. However, in genetically susceptible IL-10-/- deficient mice, SFL, but not SEL, exhibit severe inflammation and mucosal transcriptomes resembling human pouchitis. The inflammation associated with IL- 10-/- required TLR4, as animals lacking both pathways displayed little disease. Furthermore, germ-free IL10-/- mice conventionalized with SFL, but not SEL, microbiota populations develop severe colitis. These data support essential roles of stasis-induced, colon-like microbiota, TLR4- mediated colonic metaplasia, and genetic susceptibility in the development of pouchitis and possibly UC. However, these factors by themselves are not sufficient. Similarities between this model and human UC/pouchitis provide opportunities for gaining insights into the mechanistic basis of IBD and for identification of targets for novel preventative and therapeutic interventions., NIDDK DK42086 (DDRCC), UH3 DK083993, Leona and Harry Helmsley Trust (SHARE), R37 DK47722, T32 DK07074, F32 DK105728, Gastrointestinal Research Foundation of Chicago, Peter and Carol Goldman Family Research grant., 2017-06-01

BackgroundUlcerative colitis in children can have a negative effect on quality of life (QOL).MethodsWe included 16 of 31 patients who underwent colectomy for ulcerative colitis before 20 years of age between 1980 and 2005 at University of California in San Francisco Benioff Children's Hospital. A disease-specific QOL questionnaire (Inflammatory Bowel Disease Questionnaire-32), validated for adults, was used to determine QOL and an additional questionnaire addressing bowel function and reproductive health in long-term follow-up of these patients.ResultsMedian age at the time of survey was 20.3 years (17.9-25.3), and time postcolectomy was 6.9 years (4.8-9.0). Mean total score was 159.7 ± 43.3 (58-210). Two patients (12.5%) had scores of ≥ 200, 12 (75.0%) had 101 to 199, and 2 (12.5%) had ≤ 100. Patients ages 18 years or younger at the time of survey showed higher QOL, particularly in emotional health (P=0.020), social function (P=0.014), and overall QOL (P=0.009). Social function scored highest of all of the systems (median 7; interquartile range 4-7). Patients with scores ≤ 100 had repeated episodes of pouchitis (16-30) compared with the other 14 patients (0-3). Children who were diagnosed ages 12 years or younger tended to have higher QOL (p=0.072). Years postcolectomy did not correlate to QOL. Eleven patients were sexually active. Two males had feelings of impotence and decreased libido, and 6 females experienced dyspareunia. Three women tried unsuccessfully to conceive after colectomy. One woman became pregnant 4 times, each leading to miscarriage.ConclusionsYounger age at time of colectomy, diagnosis, and survey show higher QOL. Highest satisfaction was found in ability to attend school, work, and social engagements. Pouchitis continued to be an issue for a small number of the patients, with 2 patients having recurring episodes that severely affected QOL. Patients reported decreased sexual activity and fertility at the time of survey due to colectomy, especially

Ileal pouch-anal anastomosis (IPAA) is now the procedure of choice for most patients requiring proctocolectomy for ulcerative colitis. The J-shaped pouch, usually 15-20 cm in length, is easiest to construct and has functional outcomes identical to those of the more complex designs. IPAA is a complex procedure, and complications occur frequently. Despite the significant improvements this surgical advance has made on the quality of life in these patients, inflammation of the surgically created ileal pouch or pouchitis remains a major late postoperative complication that can often overshadow the benefits of this otherwise curative operation. Several inflammatory and noninflammatory complications can occur after IPAA. Pouchitis is the most common, occurring in ≈50% of patients. Whereas acute pouchitis can be treated rapidly and successfully in the majority of patients, refractory and chronic pouchitis remain therapeutic challenges to patients and physicians. The problem is believed to be caused by stasis of feces in the pouch with overgrowth of aerobic and anaerobic organisms. The size of the pouch has a significant influence on the incidence of pouchitis: a smaller pouch usually empties better than a larger pouch and so may be less susceptible to pouchitis.

type:text, To evaluate whether the pouchitis disease activity index (PDAI) alone is sufficient to select appropriate treatment plans for ulcerative colitis patients with bowel movement problems following ileal pouch-anal anastomosis (IPAA). The study included 70 patients undergoing an IPAA. For these patients, an evaluation by PDAI was performed prospectively at 1-2 years after the ileostomy closure. When the symptoms relevant to bowel movement appeared, PDAI was evaluated and metronidazole or ciprofloxacin was administered. Pouchitis was diagnosed in patients with PDAI scores of 7 or higher. The patients whose PDAI score was less than 7 and who responded to antibiotic therapy were defined as treatment responders having disease not diagnosed by PDAI (TR-NDPDAI). Pouchitis was diagnosed in 16 of the 70 enrolled patients (22.9%) using the PDAI scoring system. Of these 16 patients, 11 had acute pouchitis and 5 had chronic pouchitis. Twenty-one patients whose PDAI score was less than 7 were symptomatic. Among them, 12 were TR-NDPDAI. In patients with TR-NDPDAI, antibiotic treatment resulted in significant improvements in the PDAI score (P < 0.001) and in clinical symptoms (P < 0.001) after treatment. Antibiotic treatment was effective in a considerable number of ulcerative colitis patients whose PDAI score was less than 7 after IPAA.

Since restorative proctocolectomy (RPC) with ileal-pouch anal anastomosis (IPAA) removes the entire diseased mucosa, it has become firmly established as the standard operative procedure of choice for familial adenomatous polyposis (FAP). Many technical controversies still persist, such as mesenteric lengthening techniques, close rectal wall proctectomy, endoanal mucosectomy vs. double stapled anastomosis, loop ileostomy omission and a laparoscopic approach. Despite the complexity of the operation, IPAA is safe (mortality: 0.5-1%), it carries an acceptable risk of non-life-threatening complications (10-25%), and it achieves good long-term functional outcome with excellent patient satisfaction (over 95%). In contrast to the high incidence in patients operated for ulcerative colitis (UC) (15-20%), the occurrence of pouchitis after IPAA seems to be rare in FAP patients (0-11%). Even after IPAA, FAP patients are still at risk of developing adenomas (and occasional adenocarcinomas), either in the anal canal (10-31%) or in the ileal pouch itself (8-62%), thus requiring lifelong endoscopic monitoring. IPAA operation does not jeopardise pregnancy and childbirth, but it does impair female fecundity and has a low risk of impairment of erection and ejaculation in young males. The latter can almost completely be avoided by a careful "close rectal wall" proctectomy technique. Some argue that low risk patients (e.g. <5 rectal polyps) can be identified where ileorectal anastomosis (IRA) might be reasonable. We feel that the risk of rectal cancer after IRA means that IPAA should be recommended for the vast majority of FAP patients. We accept that in some very selected cases, based on clinical and genetics data (and perhaps influenced by patient choice regarding female fecundity), a stepwise surgical strategy with a primary IPA followed at a later age by a secondary proctectomy with IPAA could be proposed.

Patients with large bowel disease may undergo ileal pouch-anal anastomosis, in which the colon is removed and part of the distal ileum is used to construct a pelvic reservoir. Competence of the ileal pouch to ferment carbohydrates is associated with the absence of pouchitis. However, the extent to which bacterial fermentation takes place and whether it is affected by diet are unclear. We investigated fermentation of two nondigestible carbohydrates, fructooligosaccharides and resistant starch, in 15 healthy patients with an ileal pouch by using a placebo-controlled crossover design (with glucose as the placebo). Apparent fermentability of fructooligosaccharides was 83%; that of resistant starch was 46%. Resistant starch increased fecal excretion of butyrate by 69% whereas fructooligosaccharides reduced excretion of amino acid-derived isobutyrate by 94% and of isovalerate by 77%. Fructooligosaccharides also significantly increased fecal weight (651 compared with 541 g/d) and breath-hydrogen excretion (286 compared with 85 ppm x h). Bacterial fermentation of nondigestible carbohydrates in pouches takes place to an appreciable extent and in a substrate-specific manner. The relation between such fermentation and inflammation of the pouch (pouchitis) deserves study.

To evaluate whether the pouchitis disease activity index (PDAI) alone is sufficient to select appropriate treatment plans for ulcerative colitis patients with bowel movement problems following ileal pouch-anal anastomosis (IPAA). The study included 70 patients undergoing an IPAA. For these patients, an evaluation by PDAI was performed prospectively at 1-2 years after the ileostomy closure. When the symptoms relevant to bowel movement appeared, PDAI was evaluated and metronidazole or ciprofloxacin was administered. Pouchitis was diagnosed in patients with PDAI scores of 7 or higher. The patients whose PDAI score was less than 7 and who responded to antibiotic therapy were defined as treatment responders having disease not diagnosed by PDAI (TR-NDPDAI). Pouchitis was diagnosed in 16 of the 70 enrolled patients (22.9%) using the PDAI scoring system. Of these 16 patients, 11 had acute pouchitis and 5 had chronic pouchitis. Twenty-one patients whose PDAI score was less than 7 were symptomatic. Among them, 12 were TR-NDPDAI. In patients with TR-NDPDAI, antibiotic treatment resulted in significant improvements in the PDAI score (P < 0.001) and in clinical symptoms (P < 0.001) after treatment. Antibiotic treatment was effective in a considerable number of ulcerative colitis patients whose PDAI score was less than 7 after IPAA.