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 cont...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.展开更多
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-...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.展开更多
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 occ...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.展开更多
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(...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.C展开更多
Smoking is a major environmental factor that interferes in the establishment and clinical course of ulcerative colitis (UC). Firstly, the risk of smoking status impact in the development of UC is reviewed, showing tha...Smoking is a major environmental factor that interferes in the establishment and clinical course of ulcerative colitis (UC). Firstly, the risk of smoking status impact in the development of UC is reviewed, showing that current smoking has a protective association with UC. Similarly, being a former smoker is associated with an increased risk of UC. The concept that smoking could have a role in determining the inflammatory bowel disease phenotype is also discussed. Gender may also be considered, as current smoking delays disease onset in men but not in women. No clear conclusions can be driven from the studies trying to clarify whether childhood passive smoking or prenatal smoke exposure have an influence on the development of UC, mainly due to methodology flaws. The influence of smoking on disease course is the second aspect analysed. Some studies show a disease course more benign in smokers that in non-smokers, with lower hospitalizations rates, less flare-ups, lower use of oral steroids and even less risk of proximal extension. This is not verified by some other studies. Similarly, the rate of colectomy does not seem to be determined by the smoking status of the patient. The third issue reviewed is the use of nicotine as a therapeutic agent. The place of nicotine in the treatment of UC is unclear, although it could be useful in selected cases, particularly in recent ex-smokers with moderate but refractory attacks of UC. Finally, the effect of smoking cessation in UC patients is summarised. Given that smoking represents a major worldwide cause of death, for inpatients with UC the risks of smoking far outweigh any possible benefit. Thus, physicians should advise, encourage and assist UC patients who smoke to quit.展开更多
AIM： To investigate the single nucleotide polymorphisms （SNPs） in genes involved in bacterial recognition and the susceptibility to pouchitis or pouchitis severity. METHODS： Analyses of CD14 -260C〉T, CARD15/ NOD2...AIM： To investigate the single nucleotide polymorphisms （SNPs） in genes involved in bacterial recognition and the susceptibility to pouchitis or pouchitis severity. METHODS： Analyses of CD14 -260C〉T, CARD15/ NOD2 3020insC, Toll-like receptor （TLR）4 ＋896A〉G, TLR9 -1237T〉C, TLR9＋2848G〉A, and IRAKM ＋ 22148G〉A SNPs were performed in 157 ileal-pouch anal anastomosis （IPAA） patients （79 patients who did not develop pouchitis, 43 infrequent pouchitis patients, 35 chronic relapsing pouchitis patients） and 224 Italian Caucasian healthy controls. RESULTS： No significant differences were found in SNP frequencies between controls and IPAA patients. However, a significant difference in carriership frequency of the TLRg-1237C allele was found between the infrequent pouchitis and chronic relapsing pouchitis groups [P = 0.028, odd＇s ratio （OR） = 3.2, 95%CI = 1.2-8.6]. This allele uniquely represented a 4-locus TLR9 haplotype comprising both studied TLR9 SNPs in Caucasians. Carrier trait analysis revealed an enhanced combined carriership of the alleles TLR9 -1237C and CD14 -260T in the chronic relapsing pouchitis and infrequent pouchitis group （P = 0.018, OR = 4.1, 95%CI = 1.4 -12.3）. There is no evidence that the SNPs predispose to the need for IPAA surgery. The significant increase of the combined carriershoip of the CD14-260T and TLR9-1237C alleles in the chronic relapsing pouchitis group suggests that these markers identift a subgroup of IPAA patients with a rish of developing chronic or refractory pouchitis.展开更多
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 regul...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.展开更多
AIM. Pouchitis develops in ileoanal pouches in up to 50% of patients with ulcerative colitis during the first 10 years after pouch surgery while being rare in patients after proctocolectomy for familial adenomatous po...AIM. Pouchitis develops in ileoanal pouches in up to 50% of patients with ulcerative colitis during the first 10 years after pouch surgery while being rare in patients after proctocolectomy for familial adenomatous polyposis coil （FAP） syndrome. Defensins are major components of the innate immune system and play a significant role in gastrointestinal microbial homeostasis. Pouch defensin and cytokine expression were correlated with states of pouch inflammation to study their role in pouchitis.METHODS： Patients with ulcerative colitis and FAP syndrome were stratified into groups with pouches after surgery, pouches without or with pouchitis. Biopsies from terminal ileum from a healthy intestine or from normal terminal ileum of patients with ulcerative colitis served as controls, mRNA from pouches and controls was analysed for defensin and cytokine expression.RESULTS： Expression of defensins was increased in all pouches immediately after surgery, compared to ileum of controls. Initially, pouches in ulcerative colitis revealed higher defensin expression than FAP pouches. Defensin expression declined in both patient groups and increased again slightly in pouchitis in patients with ulcerative colitis. FAP pouches without pouchitis had strong expression of β-defensin hBD-1, while all other defensins remained at low levels. Cytokine expression in ulcerative colitis pouches was high, while FAP pouches showed moderately elevated cytokines only after surgery.CONCLUSION： Development of pouchitis correlates with decreased defensin expression in ulcerative colitis in addition to high expression of cytokines. The low incidence of pouchitis in FAP pouches correlates with increased expression of hBD-1 β- defensin in association with low cytokine levels.展开更多
Fecal microbiota transplantation (FMT) is considered to be a highly successful therapy for recurrent and refractory Clostridium difficile infection (CDI) based on recent clinical trials. The pathogenesis of inflammato...Fecal microbiota transplantation (FMT) is considered to be a highly successful therapy for recurrent and refractory Clostridium difficile infection (CDI) based on recent clinical trials. The pathogenesis of inflammatory bowel diseases (IBD) is thought to be due in part to perturbations in the gut microflora that disrupt homeostasis. FMT restores essential components of the microflora which could reverse the inflammatory processes observed in IBD. Case reports and series for the treatment of IBD by FMT have shown promise with regards to treatment success and safety despite the limitations of the reporting. Future studies will determine the optimal delivery and preparation of stool as well as the conditions under which the recipient will derive maximal benefit. The long term consequences of FMT with regards to infection, cancer, auto-immune, and metabolic diseases are not known and will require continued regulation and study. Despite these limitations, FMT may be beneficial for the treatment of ulcerative colitis and Crohn’s disease, particularly those with concurrent CDI or with pouchitis.展开更多
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...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.展开更多
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 ...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 展开更多
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 polyacr...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.展开更多
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 b...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.展开更多
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 comp...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.展开更多
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 ...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.展开更多
AIM: To detect the presence of human cytomegalovirus (HCMV) proteins and genes on the ileal pouch of patients with ulcerative colitis who have undergone proctocolectomy with ileal pouch-anal anastomosis (iPAA). METHOD...AIM: To detect the presence of human cytomegalovirus (HCMV) proteins and genes on the ileal pouch of patients with ulcerative colitis who have undergone proctocolectomy with ileal pouch-anal anastomosis (iPAA). METHODS: immunohistochemistry, polymerase chain reaction (PCR) and PCR sequencing methods were utilized to test the presence of HCMV in pouch specimens taken from 34 patients in 86 endoscopies. RESULTS: HCMV genes and proteins were detected in samples from 12 (35.2%) patients. The rate of detection was significant in the endoscopies from patients diagnosed with pouchitis (5 of 12, 41.6%), according to the Japanese classification of pouchitis, in comparison to patients with normal pouch (7 of 62, 11.2%; P = 0.021). in all patients with pouchitis in which the HCMV was detected, it was the first episode of pouchitis. The virus was not detected in previous biopsies taken in normal endoscopies of these patients. During the follow- up, HCMV was detected in one patient with recurrent pouchitis and in 3 patients whose pouchitis episodes improved but whose positive endoscopic findings persisted. CONCLUSION: HCMV can take part in the inflammatory process of the pouch in some patients with ulcerative colitis who have undergone proctocolectomy with iPAA.展开更多
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)....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.展开更多
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 chro...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).展开更多
基金Supported by The Association for International Cancer Research(AICRto Dr.Al-Hassi HO)+6 种基金ScotlandFunded by the AICRgrant No.120234a BBSRC Strategic Research Grant(to English N and Knight SCWMNIP33458)the St Mark’s Hospital FoundationUnited Kingdom
文摘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.
基金Supported by Academician Jie-Shou Li Intestinal Barrier Research Foundation,No.LJS_201008
文摘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.
文摘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.
文摘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.C
基金Supported by The Instituto de Salud Caslos Ⅲ, from the Spanish Ministry of Health (CIBEREHD)
文摘Smoking is a major environmental factor that interferes in the establishment and clinical course of ulcerative colitis (UC). Firstly, the risk of smoking status impact in the development of UC is reviewed, showing that current smoking has a protective association with UC. Similarly, being a former smoker is associated with an increased risk of UC. The concept that smoking could have a role in determining the inflammatory bowel disease phenotype is also discussed. Gender may also be considered, as current smoking delays disease onset in men but not in women. No clear conclusions can be driven from the studies trying to clarify whether childhood passive smoking or prenatal smoke exposure have an influence on the development of UC, mainly due to methodology flaws. The influence of smoking on disease course is the second aspect analysed. Some studies show a disease course more benign in smokers that in non-smokers, with lower hospitalizations rates, less flare-ups, lower use of oral steroids and even less risk of proximal extension. This is not verified by some other studies. Similarly, the rate of colectomy does not seem to be determined by the smoking status of the patient. The third issue reviewed is the use of nicotine as a therapeutic agent. The place of nicotine in the treatment of UC is unclear, although it could be useful in selected cases, particularly in recent ex-smokers with moderate but refractory attacks of UC. Finally, the effect of smoking cessation in UC patients is summarised. Given that smoking represents a major worldwide cause of death, for inpatients with UC the risks of smoking far outweigh any possible benefit. Thus, physicians should advise, encourage and assist UC patients who smoke to quit.
文摘AIM： To investigate the single nucleotide polymorphisms （SNPs） in genes involved in bacterial recognition and the susceptibility to pouchitis or pouchitis severity. METHODS： Analyses of CD14 -260C〉T, CARD15/ NOD2 3020insC, Toll-like receptor （TLR）4 ＋896A〉G, TLR9 -1237T〉C, TLR9＋2848G〉A, and IRAKM ＋ 22148G〉A SNPs were performed in 157 ileal-pouch anal anastomosis （IPAA） patients （79 patients who did not develop pouchitis, 43 infrequent pouchitis patients, 35 chronic relapsing pouchitis patients） and 224 Italian Caucasian healthy controls. RESULTS： No significant differences were found in SNP frequencies between controls and IPAA patients. However, a significant difference in carriership frequency of the TLRg-1237C allele was found between the infrequent pouchitis and chronic relapsing pouchitis groups [P = 0.028, odd＇s ratio （OR） = 3.2, 95%CI = 1.2-8.6]. This allele uniquely represented a 4-locus TLR9 haplotype comprising both studied TLR9 SNPs in Caucasians. Carrier trait analysis revealed an enhanced combined carriership of the alleles TLR9 -1237C and CD14 -260T in the chronic relapsing pouchitis and infrequent pouchitis group （P = 0.018, OR = 4.1, 95%CI = 1.4 -12.3）. There is no evidence that the SNPs predispose to the need for IPAA surgery. The significant increase of the combined carriershoip of the CD14-260T and TLR9-1237C alleles in the chronic relapsing pouchitis group suggests that these markers identift a subgroup of IPAA patients with a rish of developing chronic or refractory pouchitis.
基金supported by Natural Science Foundation of China(Grant Number:8150041674)
文摘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.
基金Supported by the Deutsche Forschungsgemeinschaft(SFB 617)in part by a grant of the Finnish Gastroenterological Society.
文摘AIM. Pouchitis develops in ileoanal pouches in up to 50% of patients with ulcerative colitis during the first 10 years after pouch surgery while being rare in patients after proctocolectomy for familial adenomatous polyposis coil （FAP） syndrome. Defensins are major components of the innate immune system and play a significant role in gastrointestinal microbial homeostasis. Pouch defensin and cytokine expression were correlated with states of pouch inflammation to study their role in pouchitis.METHODS： Patients with ulcerative colitis and FAP syndrome were stratified into groups with pouches after surgery, pouches without or with pouchitis. Biopsies from terminal ileum from a healthy intestine or from normal terminal ileum of patients with ulcerative colitis served as controls, mRNA from pouches and controls was analysed for defensin and cytokine expression.RESULTS： Expression of defensins was increased in all pouches immediately after surgery, compared to ileum of controls. Initially, pouches in ulcerative colitis revealed higher defensin expression than FAP pouches. Defensin expression declined in both patient groups and increased again slightly in pouchitis in patients with ulcerative colitis. FAP pouches without pouchitis had strong expression of β-defensin hBD-1, while all other defensins remained at low levels. Cytokine expression in ulcerative colitis pouches was high, while FAP pouches showed moderately elevated cytokines only after surgery.CONCLUSION： Development of pouchitis correlates with decreased defensin expression in ulcerative colitis in addition to high expression of cytokines. The low incidence of pouchitis in FAP pouches correlates with increased expression of hBD-1 β- defensin in association with low cytokine levels.
文摘Fecal microbiota transplantation (FMT) is considered to be a highly successful therapy for recurrent and refractory Clostridium difficile infection (CDI) based on recent clinical trials. The pathogenesis of inflammatory bowel diseases (IBD) is thought to be due in part to perturbations in the gut microflora that disrupt homeostasis. FMT restores essential components of the microflora which could reverse the inflammatory processes observed in IBD. Case reports and series for the treatment of IBD by FMT have shown promise with regards to treatment success and safety despite the limitations of the reporting. Future studies will determine the optimal delivery and preparation of stool as well as the conditions under which the recipient will derive maximal benefit. The long term consequences of FMT with regards to infection, cancer, auto-immune, and metabolic diseases are not known and will require continued regulation and study. Despite these limitations, FMT may be beneficial for the treatment of ulcerative colitis and Crohn’s disease, particularly those with concurrent CDI or with pouchitis.
文摘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.
基金Supported by unrestricted grants from Janssen Inc.(Canada),Abbvie(Canada),Ferring Canada Inc.,and Actavis Canada Inc.(partly,to Dr Zezos)
文摘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
文摘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.
文摘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.
文摘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.
文摘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.
文摘AIM: To detect the presence of human cytomegalovirus (HCMV) proteins and genes on the ileal pouch of patients with ulcerative colitis who have undergone proctocolectomy with ileal pouch-anal anastomosis (iPAA). METHODS: immunohistochemistry, polymerase chain reaction (PCR) and PCR sequencing methods were utilized to test the presence of HCMV in pouch specimens taken from 34 patients in 86 endoscopies. RESULTS: HCMV genes and proteins were detected in samples from 12 (35.2%) patients. The rate of detection was significant in the endoscopies from patients diagnosed with pouchitis (5 of 12, 41.6%), according to the Japanese classification of pouchitis, in comparison to patients with normal pouch (7 of 62, 11.2%; P = 0.021). in all patients with pouchitis in which the HCMV was detected, it was the first episode of pouchitis. The virus was not detected in previous biopsies taken in normal endoscopies of these patients. During the follow- up, HCMV was detected in one patient with recurrent pouchitis and in 3 patients whose pouchitis episodes improved but whose positive endoscopic findings persisted. CONCLUSION: HCMV can take part in the inflammatory process of the pouch in some patients with ulcerative colitis who have undergone proctocolectomy with iPAA.
文摘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.
文摘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).
