Inflammatory pouch disease: The spectrum of pouchitis

Restorative proctocolectomy with ileal-pouch anal anastomosis(IPAA) is the operation of choice for medically refractory ulcerative colitis(UC), for UC with dysplasia, and for familial adenomatous polyposis(FAP). IPAA can be a treatment option for selected patients with Crohn's colitis without perianal and/or small bowel disease. The term "pouchitis" refers to nonspecific inflammation of the pouch and is a common complication in patients with IPAA; it occurs more often in UC patients than in FAP patients. This suggests that the pathogenetic background of UC may contribute significantly to the development of pouchitis. The symptoms of pouchitis are many, and can include increased bowel frequency, urgency, tenesmus, incontinence, nocturnal seepage, rectal bleeding, abdominal cramps, and pelvic discomfort. The diagnosis of pouchitis is based on the presence of symptoms together with endoscopic and histological evidence of inflammation of the pouch. However, "pouchitis" is a general term representing a wide spectrum of diseases and conditions, which can emerge in the pouch. Based on the etiology we can sub-divide pouchitis into 2 groups: idiopathic and secondary. In idiopathic pouchitis the etiology and pathogenesis are still unclear, while in secondary pouchitis there is an association with a specific causative or pathogenetic factor. Secondary pouchitis can occur in up to 30% of cases and can be classified as infectious, ischemic, non-steroidal antiinflammatory drugs-induced, collagenous, autoimmuneassociated, or Crohn's disease. Sometimes, cuffitis or irritable pouch syndrome can be misdiagnosed as pouchitis. Furthermore, idiopathic pouchitis itself can be sub-classified into types based on the clinical pattern, presentation, and responsiveness to antibiotic treatment. Treatment differs among the various forms of pouchitis. Therefore, it is important to establish the correct diagnosis in order to select the appropriatetreatment and further management. In this editorial, we present the spectrum of pouchitis and the specific features related to the diagnosis and treatment of the various forms.

Diversion colitis and pouchitis: A mini-review

Diversion colitis is characterized by inflammation of the mucosa in the defunctioned segment of the colon after colostomy or ileostomy. Similar to diversion colitis, diversion pouchitis is an inflammatory disorder occurring in the ileal pouch, resulting from the exclusion of the fecal stream and a subsequent lack of nutrients from luminal bacteria. Although the vast majority of patients with surgically-diverted gastrointestinal tracts remain asymptomatic, it has been reported that diversion colitis and pouchitis might occur in almost all patients with diversion. Surgical closure of the stoma, with reestablishment of gut continuity, is the only curative intervention available for patients with diversion disease. Pharmacologic treatments using short-chain fatty acids, mesalamine, or corticosteroids are reportedly effective for those who are not candidates for surgical reestablishment; however, there are no established assessment criteria for determining the severity of diversion colitis, and no management strategies to date. Therefore, in this mini-review, we summarize and review various recently-reported treatments for diversion disease. We are hopeful that the information summarized here will assist physicians who treat patients with diversion colitis and pouchitis, leading to better case management.

Fecal microbiota in pouchitis and ulcerative colitis

AIM To investigate the changes in microbiota in feces of patients with ulcerative colitis(UC) and pouchitis using genomic technology.METHODS Fecal samples were obtained from UC patients with or without an ileal pouch-anal anastomosis(IPAA) procedure, as well as healthy controls. The touchdown polymerase chain reaction technique was used to amplify the whole V3 region of the 16 S r RNA gene, which was transcribed from DNA extracted from fecal samples. Denaturing gradient gel electrophoresis was used to separate the amplicons. The band profiles and similarity indices were analyzed digitally. The predominant microbiota in different groups was confirmed by sequencing the 16 S rR NA gene. RESULTS Microbial biodiversity in the healthy controls was significantly higher compared with the UC groups(P < 0.001) and IPAA groups(P < 0.001). Compared with healthy controls, the UC patients in remission and those in the mildly active stage, the predominant species in patients with moderately and severely active UC changed obviously. In addition, the proportion of the dominant microbiota, which was negatively correlated with the disease activity of UC(r =-6.591, P < 0.01),was decreased in pouchitis patients. The numbers of two types of bacteria, Faecalibacterium prausnitzii and Eubacterium rectale, were reduced in UC. Patients with pouchitis had an altered microbiota composition compared with UC patients. The microbiota from pouchitis patients was less diverse than that from severely active UC patients. Sequencing results showed that similar microbiota, such as Clostridium perfringens, were shared in both UC and pouchitis.CONCLUSION Less diverse fecal microbiota was present in patients with UC and pouchitis. Increased C. perfringens in feces suggest its role in the exacerbation of UC and pouchitis.

Role of intestinal flora imbalance in pathogenesis of pouchitis

Objective: To discuss the role of intestinal flora imbalance in the pathogenesis of pouchitis. Methods: The puochitis rat model was established and the faeces sample and the mucous membrane sample were collected regularly, in which the bacterial nucleic acids were extracted for quantitative analysis of the intestinal flora in the samples through using the real-time quantitative PCR technique and high energy sequencing technology. Results: The disorder phenomenon of the intestinal flora appeared at the 7th day of the experiment, and the pouchitis was presented at the 21 th day of the experiment. At the 31 th day of the experiment, compared to control group and non-pouchitis group, the quantity of Bifidobacterium and the Lactobacillusof the pouchitis model rats in the mucous membrane sample and the faeces sample were significantly decreased(P<0.05), and the Bacteroidetes, Faecalibacterium prausnitzii and 桛 Clostridium leptum subgroup in the mucous membrane of pouchitis were significantly decreased(P<0.05). The Clostridium coccoides group was the main flora in the mucous membrane of pouchitis, the bacterial diversity of non-puochitis group and control group was significantly higher than that of the puochitis group(P<0.05). Conclusions: The intestinal flora imbalance is one of the factors that cause the incidence of the pouhitis; this study provides a clue of the pathogenesis and treatment direction of the intestinal inflammatory disease.

Antibiotics and probiotics in chronic pouchitis:A comparative proteomic approach

AIM:To profile protein expression in mucosal biopsies from patients with chronic refractory pouchitis following antibiotic or probiotic treatment,using a comparative proteomic approach. METHODS:Two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ ionization-time of flight mass spectrometry were used to characterize the changes related to antibiotic therapy in the protein expression profiles of biopsy samples from patients with chronic refractory pouchitis.The same proteomic approach was applied to identify differentially expressed proteins in the non-inflamed pouch before and after probiotic administration. RESULTS:In the first set of 2D gels,26 different proteins with at least 2-fold changes in their expression levels between the pouchitis condition and antibiotic-induced remission were identified.In the second set of analysis,the comparison between mucosal biopsy proteomes in the normal and probiotic-treated pouch resulted in 17 significantly differently expressed proteins.Of these,8 exhibited the same pattern of deregulation as in the pouchitis/pouch remission group. CONCLUSION:For the first time,2D protein maps of mucosal biopsies from patients with ileal pouch-anal anastomosis were provided,and differentially expressed proteins following antibiotic/probiotic treatment were identified.

Relationship between pouch microbiota and pouchitis following restorative proctocolectomy for ulcerative colitis

Restorative proctocolectomy with ileal pouch-anal anastomosis(IPAA)has become the surgical treatment of choice for many patients with medically refractory ulcerative colitis(UC)and familial adenomatous polyposis(FAP).UC patients with IPAA(UC-IPAA)are,nevertheless,susceptible to inflammatory and noninflammatory sequelae such as pouchitis,which is only rarely noted in FAP patients with IPAA.Pouchitis is the most frequent long-term complication of UC-IPAA patients,with a cumulative prevalence of up to 50%.Although the aetiology of pouchitis remains unclear,accumulating evidence suggests that a dysbiosis of the pouch microbiota and an abnormal mucosal immune response are implicated in its pathogenesis.Studies using culture and molecular techniques have detected a dysbiosis of the pouch microbiota in patients with pouchitis.Risk factors,genetic associations,and serological markers suggest that interactions between the host immune response and the pouch microbiota underlie the aetiology of this idiopathic inflammatory condition.This systematic review focuses on the dysbiosis of the microbiota that inhabit the pouch in UC and FAP patients and its interaction with the mucosal immune system.A metaanalysis was not attempted due to the highly heterogeneous microbiota composition and the different detection methods used by the various studies.Although no specific bacterial species,genus,or family has as yet been identified as pathogenic,there is evidence that a dysbiosis characterized by decreased gut microbiota diversity in UC-IPAA patients may,in genetically predisposed subjects,lead to aberrant mucosal immune regulation triggering an inflammatory process.

Infliximab for the treatment of pouchitis

Pouchitis is not a rare complication that develops after an ileal-pouch anastomosis, performed after colectomy in patients refractory to treatment or with complicated ulcerative colitis. This condition may become chronic and unresponsive to medical therapies, including corticosteroids, antibiotics and probiotics. The advent of biological therapies(tumor necrosis factor-α inhibitors) has changed the course of these complications. In particular, in these cases, infliximab(IFX) may represent a safe and effective therapy in order to avoid the subsequent operation for a permanent ileostomy. This article reviews the therapeutic effects of one of the most widely used anti-tumor necrosis factor-α molecules, IFX, for the treatment of complicated pouchitis(refractory to conventional treatment and/or fistulizing).

Lactobacillus acidophilus alleviates pouchitis after ileal pouch-anal anastomosis in rats

AIM To assess the therapeutic potential of Lactobacillus acidophilus(LA) for the treatment of pouchitis in a rat model.METHODS Sprague Dawley rats underwent proctocolectomy and ileal pouch-anal anastomosis followed by administration of dextran sulfate sodium(DSS) to induce pouchitis. Rats with pouchitis were randomly divided into three groups: no intervention(NI), normal saline(NS, 3 m L/d normal saline for 7 d), and LA(3 m L/d LA at 1× 1010 colony-forming units for 7 d). General body condition was recorded and pouch specimens were obtained for histological examination. m RNA expression levels of interleukin(IL)-1β, IL-6, IL-10, and tumor necrosis factor-α were determined by RT-PCR. Zonula occludens protein 1(ZO-1) levels were measured by immunohistochemistry. RESULTS LA reduced weight loss associated with pouchitis(P < 0.05) and improved the symptoms of pouchitis in rats. Compared with the NI and NS groups, rats in the LAgroup showed earlier disappearance of hematochezia(6.17 ± 0.75, 6.50 ± 0.55, 3.17 ± 0.75, P < 0.05) and higher fecal scores(2.67 ± 0.48, 2.50 ± 0.51, 4.42 ± 0.50, respectively, P < 0.05). Histological scores were also lower in the LA group compared with the other two groups(7.17 ± 0.98, 8.00 ± 0.89, 4.00 ± 0.89, respectively, P < 0.05). m RNA expression levels of IL-1β, IL-6, and tumor necrosis factor-α were significantly reduced, while IL-10 m RNA levels were significantly increased in the LA group(P < 0.05, respectively). ZO-1 protein levels were also significantly increased after administration of LA(P < 0.05). CONCLUSION LA alleviates pouchitis induced by DSS after ileal pouchanal anastomosis by decreasing pro-inflammatory factors and increasing anti-inflammatory factors, and restoring ZO-1 expression in the mucosa.

Effectiveness of vedolizumab treatment in two different anti-tumor necrosis factor alpha refractory pouchitis: A case report

BACKGROUND Refractory pouchitis is a common cause of pouch failure,which may require surgical excision of the pouch or permanent diversion.We aimed to show the effect of vedolizumab on treatment of the patient with refractory pouchitis.CASE SUMMARY A 32-year-old male with pancolonic ulcerative colitis since the age of 25 with primary failure of infliximab and mesalamine and intolerance of azathioprine,underwent a total proctocolectomy with ileal pouch-anal anastomosis in 2012.He developed chronic diarrhea in 2014,which was watery,30 per day and accompanied with blood and mucus affecting his quality of life.CONCLUSION Vedolizumab is safe and effective in the management of anti-tumor necrosis factor alpha refractory pouchitis.

The pathogenesis of primary pouchitis following ileal pouch-anal anastomosis: a review of current hypotheses

Primary pouchitis is a common complication of ileal pouch-anal anastomosis following proctocolectomy in patients treated for ulcerative colitis (UC), but is un-usual for those treated for familial adenomatous polyposis (FAP). While a number of theories as to the pathogenesis of this inflammatory condition have been proposed, no single one has been wholly satis-factory. Much research has been devoted to investi-gating a link between the pathogenic factors involved in UC, but not FAP, and those underlying pouchitis. The contribution of sulfate-producing bacteria has also been explored. The role of other intraluminal factors, such as short chain fatty acids and unconju-gated bile salts, has also been investigated. A unifying theory of a multi-step process might explain the pathogenesis of pouchitis, but further research is re-quired to proof causation. It is likely that pouchitis develops as a result of a combination of genetic, im-munological, microbial and metabolic factors. Future insight into the causes of pouchitis may eventually allow for the development of more effective treat-ments.

Role of prebiotics, probiotics, and synbiotics in management of inflammatory bowel disease: Current perspectives

Experimental evidence supports the fact that changes in the bowel microflora due to environmental or dietary factors have been investigated as implicating factors in the etiopathogenesis of inflammatory bowel disease(IBD).The amassing knowledge that the inhabited microbiome regulates the gut physiology and immune functions in IBD,has led researchers to explore the effectiveness of prebiotics,probiotics,and synbiotics in treating IBD.This therapeutic approach focuses on restoring the dynamic balance between the microflora and host defense mechanisms in the intestinal mucosa to prevent the onset and persistence of intestinal inflammation.Numerous microbial strains and carbohydrate blends,along with their combinations have been examined in experimental colitis models and clinical trials,and the results indicated that it can be an attractive therapeutic strategy for the suppression of inflammation,remission induction,and relapse prevention in IBD with minimal side effects.Several mechanisms of action of probiotics(for e.g.,Lactobacillus species,and Bifidobacterium species)have been reported such as suppression of pathogen growth by releasing certain antimicrobial mediators(lactic and hydrogen peroxide,acetic acid,and bacteriocins),immunomodulation and initiation of an immune response,enhancement of barrier activity,and suppression of human T-cell proliferation.Prebiotics such as lactulose,lactosucrose,oligofructose,and inulin have been found to induce the growth of certain types of host microflora,resulting in an enriched enteric function.These non-digestible food dietary components have been reported to exert anti-inflammatory effects by inhibiting the expression of tumor necrosis factor-α-related cytokines while augmenting interleukin-10 levels.Although proand prebiotics has established their efficacy in healthy subjects,a better understanding of the luminal ecosystem is required to determine which specific bacterial strain or combination of probiotics and prebiotics would prove to be the ideal treatment for IBD.Clinical trials,however,have given some conflicting results,requiring the necessity to cite the more profound clinical effect of these treatments on IBD remission and prevention.The purpose of this review article is to provide the most comprehensive and updated review on the utility of prebiotics,probiotics,and synbiotics in the management of active Crohn’s disease and ulcerative colitis/pouchitis.

Correction to“Role of prebiotics,probiotics,and synbiotics in management of inflammatory bowel disease:Current perspectives”

Correction to“Roy S,Dhaneshwar S.Role of prebiotics,probiotics,and synbiotics in management of inflammatory bowel disease:Current perspectives.World J Gastroenterol 2023;29:2078-2100[PMID:37122604 DOI:10.3748/wjg.v29.i14.20-78]”.In this article,a correction note is to be added.

Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer

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.

Role of exercise in preventing and restoring gut dysbiosis in patients with inflammatory bowel diseases:A review

Inflammatory bowel diseases(IBD)include a spectrum of chronic inflammatory disorders of the gastrointestinal tract whose pathogenesis is yet to be elucidated.The intestinal microbiome has been studied as a causal component,with certain microbiotic alterations having been observed in subtypes of IBD.Physical exercise is a modulator of the intestinal microbiome,causing shifts in its composition that are partially corrective of those observed in IBD;furthermore,physical exercise may be beneficial in patients with certain IBD subtypes.This review studies the effects of physical exercise on the human gut microbiome while investigating pathophysiologic mechanisms that could explain physical activity’s clinical effects on patients with IBD.

Role of wireless capsule endoscopy in the follow-up of inflammatory bowel disease

The introduction of wireless capsule endoscopy in 2000 has revolutionized our ability to visualize parts of the small bowel mucosa classically unreached by the conventional endoscope, and since the recent introduction of colon capsule endoscopy, a promising alternative method has been available for the evaluation of large bowel mucosa. The advantages of wireless capsule endoscopy include its non-invasive character and its ability to visualize proximal and distal parts of the intestine, while important disadvantages include the procedure's inability of tissue sampling and significant incompletion rate. Its greatest limitation is the prohibited use in cases of known or suspected stenosis of the intestinal lumen due to high risk of retention. Wireless capsule endoscopy plays an important role in the early recognition of recurrence, on Crohn's disease patients who have undergone ileocolonic resection for the treatment of Crohn's disease complications, and in patients' management and therapeutic strategy planning, before obvious clinical and laboratory relapse. Although capsule endoscopy cannot replace traditional endoscopy, it offers valuable information on the evaluation of intestinal disease and has a significant impact on disease reclassification of patients with a previous diagnosis of ulcerative colitis or inflammatory bowel disease unclassified/indeterminate colitis. Moreover, it may serve as an effective alternative where colonoscopy is contraindicated and in cases with incomplete colonoscopy studies. The use of patency capsule maximizes safety and is advocated in cases of suspected small or large bowel stenosis.

Serologic and laboratory markers in prediction of the disease course in inflammatory bowel disease

The search for biologic markers that can assess the natural history and perhaps predict the course of individual's disease including response to treatments over time has become an important focus of inflammatory bowel disease research.The knowledge of an individual's prognosis can help physicians and patients make important management decisions and aid communication on risk and benefits of disease and treatment.

Probiotics in inflammatory bowel disease: Pathophysiological background and clinical applications

Ulcerative colitis and Crohn's disease, collectively termed the inflammatory bowel diseases(IBD), are chronic inflammatory disorders of the gastrointestinal tract. A "dysbiotic" relationship between the commensal gut flora and the intestinal mucosa-associated immune system has been at the core of the pathogenesis of these conditions. Probiotics are "good bacteria" with the ability to benefit the health of the host and their therapeutic application has been studied in IBD. The theoretical basis for such utilization relies upon the ability of probiotic microorganisms to interfere with the dysregulated homeostasis that takes place in IBD and restore the immune-bacterial interaction at the intestinal mucosa. Proposed mechanisms of action include the reconstitution of altered flora composition, enhancement of the integrity of the epithelial barrier, promotion of tolerogenic action by dendritic cells, strengthening of the defensive mechanisms of the innate immunity, and the suppression of pro-inflammatory adaptive immune responses. Despite this abundance of supporting experimental evidence, clinical application of probiotics in IBD has been disappointing. Possible explanations for such discrepancy include the great diversity of microorganisms that fall under the definition of probiotics, the lack of standardization of dosages and administration schemes, the heterogeneity between clinical trials, and the inclusion in the treatment arms of patients with a large variety of clinical phenotypes. Addressing these important issues will be critical for the optimal usage of probiotic-based therapies for patients with IBD.

Orphan patients with inflammatory bowel disease-when we treat beyond evidence

Inflammatory bowel disease(IBD)is a chronic condition that requires continuous medical treatment.To date,the medical management of patients with moderatelyto-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.

高压氧治疗慢性抗生素难治性缺血性储袋炎

Hyperbaric oxygen therapy(HBOT)has been shown to be efficacious in treating various conditions,including perianal Crohn’s disease.Here we present a case of a 59-year-old male with a history of ulcerative colitis,who underwent a total proctocolectomy and two-stage J-pouch construction.He later developed chronic antibiotic-refractory pouchitis with endoscopic features of ischemia.At the completion of HOBT-a total of 20 sessions of 100%oxygen at 2.5-3.0 atmospheres absolute for 60-90 minutes per session-a repeat pouchoscopy showed marked improvement of endoscopic mucosal inflammation.HBOT is known to increase tissue oxygenation,reduce tissue hypoxia,alter inflammatory pathways and promote tissue healing.This case demonstrated the therapeutic role of HBOT as well as the possible disease mechanism in chronic antibiotic-refractory pouchitis.

NOD2/CARD15突变的回肠储袋患者的自身免疫性疾病

Pouchitis is common in ulcerative colitis patients undergoing total proctocolectomy with ileal pouch-anal anastomosis,and chronic antibiotic-refractory pouchitis occurs in a subgroup of the patients.Auto-inflammatory diseases are characterized by systemic inflammation,manifesting as periodic fever,rash,arthritis,and serositis.We describe two cases with ulcerative colitis and an ileal pouch,who presented with extra-intestinal manifestations and genetic features atypical for inflammatory bowel disease alone.Case 1 had a spectrum of clinical manifestations including refractory pouchitis,intermittent fevers,polyarthralgia,and pericarditis.Case 2 presented with oral ulcers,migratory oligoarthritis,and periodic papular rash.Genetic testing in both cases revealed mutations of the NOD2/CARD15 gene,including the IVS8þ158 mutation commonly detected among patients with NOD2-associated auto-inflammatory disease.Both of the patients demonstrated clinical improvement of these diverse systemic complaints following treatment with immunosuppressive and anti-inflammatory therapies.