粘附分子与炎症性肠病

粘附分子是一类介导细胞与细胞、细胞与基质间相互作用的糖蛋白，某些粘附分子在炎症性肠病中存在异常表达，其在炎症性肠病中的作用机制甚为复杂，抗粘附分子的单克隆抗体治疗炎症性肠病已显示其应用前景，随着对粘附分子及作用机制的深入研究，可望制定出更为有效的治疗措施。

Probiotics and prebiotics in chronic inflammatory bowel diseases

The prokaryotic and eukaryotic cells of the colon exist in a highly complex, but harmonious relationship. Disturbances in this remarkable symbiosis can result in the development of inflammatory bowel diseases (IBD). Although the etiology of IBD is not entirely understood, it is known that the chronic inflammation of Crohn’s disease, ulcerative colitis and chronic pouchitis are a result of an overly aggressive immune response to the commensal intestinal flora in genetically susceptible hosts. Recent studies have enhanced our ability to understand the interaction between the host and its intestinal microflora and the role the microflora plays in maintaining intestinal homeostasis. As we begin to understand the benefi ts conferred to the intestine by the microflora, the notion of modifying the composition of the bacterial load to improve human health has arisen. A signifi cant body of research now exists investigating the role of probiotics and prebiotics in ameliorating chronic intestinal inflammation. This article will begin with an overview of the role of the commensal microflora in maintaining mucosal immune homeostasis, and how a dysregulated immune response to the intestinal microflora results in IBD. This will be followed by a summary of the use of probiotics and prebiotics in experimental and human IBD.

Therapeutic approaches targeting intestinal microflora in inflammatory bowel disease

Inflammatory bowel diseases, ulcerative colitis, and Crohn＇s disease, are chronic intestinal disorders of unknown etiology in which in genetically susceptible individuals, the mucosal immune system shows an aberrant response towards commensal bacteria. The gastrointestinal tract has developed ingenious mechanisms to coexist with its autologous microflora, but rapidly responds to invading pathogens and then returns to homeostasis with its commensal bacteria after the pathogenic infection is cleared. In case of disruption of this tightly-regulated homeostasis, chronic intestinal inflammation may be induced. Previous studies showed that some commensal bacteria are detrimental while others have either no influence or have a protective action. In addition, each host has a genetically determined response to detrimental and protective bacterial species. These suggest that therapeutic manipulation of imbalance of microflora can influence health and disease. This review focuses on new insights into the role of commensal bacteria in gut health and disease, and presents recent findings in innate and adaptive immune interactions. Therapeutic approaches to modulate balance of intestinal microflora and their potential mechanisms of action are also discussed.

Innovative therapeutics for inflammatory bowel disease

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract, which clinically present as one of two disorders, Crohn's disease or ulcerative colitis. Mainstays of drug treatments for IBD include aminosalicylates, corticosteroids and immunosuppressants such as azathioprine, methotrexate and cyclosporin. Advances in basic research of the pathophysiological process in IBD have been applied to generate a variety of new therapeutics targeting at different levels of the inflammatory processes. New therapies are classified as: (1) Anti-TNFα antibodies; (2) Recombinant cytokines; (3) Selective adhesion blockade; (4) Growth factors; (5) Innate immunostimulation; (6) Nucleic acid based therapies; (7) Gene therapy; (8) Autologous bone-marrow transplantation; (9) Helminths and (10) Extracorporeal immunomodulation. All treatments have the potential to provide more effective and safe treatment for IBD.

Disease impact on the quality of life of children with inflammatory bowel disease

To assess the impact of disease characteristics on the quality of life (QOL) in children with inflammatory bowel diseases (IBD).METHODSThis was a cross-sectional study conducted at the First Department of Pediatrics of the University of Athens at the “Aghia Sophia” Children’s Hospital. Children diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC), who were followed as outpatients or during a hospitalization, participated, after informed consent was obtained from their legal representative. QOL was assessed by the IMPACT-III questionnaire. Demographic data and disease characteristics were also collected. Statistical analyses included parametric (Student’s t-test and Pearson’s r) and non-parametric (Mann-Whitney test, Fisher’s test and Spearman’s rho) procedures.RESULTSNinety-nine patients (UC: 37, 73.0% females, CD: 62, 51.6% females), aged 12.8 ± 2.6 years were included. Overall, as well as, sub-domain scores did not differ between UC and CD (overall score: 73.9 ± 13.3 vs 77.5 ± 11.2, respectively, P = 0.16). In the entire sample, total score was related to physician’s global assessment (PGA, patients classified as “mild/moderate” active disease had, on average, 14.8 ± 2.7 points lower total scores compared to those “in remission”, P < 0.001) and age at IMPACT completion (Pearson’s r = 0.29, P = 0.05). Disease activity assessed by the indices Pediatric Ulcerative Colitis activity index, Pediatric Crohn’s disease activity index or PGA was significantly associated with all subdomains scores. Presence of extraintestinal manifestations had a negative impact on emotional and social functioning domains.CONCLUSIONDisease activity is the main correlate of QOL in children with IBD, underlining the importance of achieving and sustaining clinical remission

Risk factor analysis for meta plastic gastritis in Koreans

AIM： To conduct a retrospective study to determine the risk factors for development of metaplastic gastritis in Korean population. METHODS： The database of 113449 subjects who underwent a gastroscopy for the purpose of a regular check-up at center for health promotion, Samsung medical center during 5 years was collected and retrospectively analyzed. Among them, 5847 subjects who had endoscopically diagnosed as a metaplastic gastritis or 10076 normal as well as answered to questionnaire were included for present study. The subjects were divided into 2 groups; Group Ⅰ, normal and Group Ⅱ, metaplastic gastritis. Age, gender, Helicobacter pylori （H pylori） seropositivity, body mass index （BMI）, family history of cancer, smoking, alcohol consumption, total daily calories, folate and salt intake and dietary habit （out-eating, overeating, irregular eating） were retrieved from questionnaire or electronic medical record and compared between group Ⅰ and group Ⅱ. RESULTS： The prevalence of group Ⅱwas 11% （13578/113449） increasing its prevalence with age （P=0.000）. But, there was no significant association between 2 groups in BMI, family history of cancer, alcohol consumption, total daily calories, folate and salt intake and dietary habit （out-eating, overeating, irregular eating）. Old age （P=0.000）, male gender （P=0.000）, H pylori seropositivity （P= 0.010） and current smoker （P=0.000） were significantly more common in group II at multiple logistic regression model. CONCLUSION： Our data suggested that old age, male gender, H pylori seropositivity and smoking were risk factors for metaplastic gastritis, precancerous lesion of gastric cancer.

Effects of Helicobacter pylori eradication on atrophic gastritis and intestinal metaplasia: A 3-year follow-up study

AIM: To investigate the effect of H pylori eradication on atrophic gastritis and intestinal metaplasia (IM).METHODS: Two hundred and fifty-nine patients with atrophic gastritis in the antrum were included in the study, 154 patients were selected for H pylori eradication therapy and the remaining 105 patients served as untreated group. Gastroscopy and biopsies were performed both at the beginning and at the end of a 3-year follow-up study. Gastritis was graded according to the updated Sydney system.RESULTS: One hundred and seventy-nine patients completed the follow-up, 92 of them received H pylori eradication therapy and the remaining 87 H pyloriinfected patients were in the untreated group. Chronic gastritis, active gastritis and the grade of atrophy significantly decreased in H pylori eradication group (P＜0.01). However, the grade of IM increased in H pylori -infected group (P＜0.05).CONCLUSION: H pylori eradication may improve gastric mucosal inflammation, atrophy and prevent the progression of IM.

Intestinal bile acid physiology and pathophysiology

Bile acids (BAs) have a long established role in fat digestion in the intestine by acting as tensioactives, due to their amphipatic characteristics. BAs are reabsorbed very efficiently by the intestinal epithelium and recycled back to the liver via transport mechanisms that have been largely elucidated. The transport and synthesis of BAs are tightly regulated in part by specific plasma membrane receptors and nuclear receptors. In addition to their primary effect, BAs have been claimed to play a role in gastrointestinal cancer, intestinal inflammation and intestinal ionic transport. BAs are not equivalent in any of these biological activities, and structural requirements have been generally identified. In particular, some BAs may be useful for cancer chemoprevention and perhaps in inflammatory bowel disease, although further research is necessary in this field. This review covers the most recent developments in these aspects of BA intestinal biology.

Qualitative and quantitative analyses of the bifidobacterial microbiota in the colonic mucosa of patients with colorectal cancer, diverticulitis and inflammatory bowel disease

AIM： To characterize the bifidobacterial microbiota of the colonic mucosa in patients with colon cancer, inflammatory bowel disease or diverticulitis. METHODS： A sample of the distal colonic mucosa was taken during surgery from a total of 34 patients, twenty-one with diagnosed colorectal cancer, nine with diverticulitis and four with inflammatory bowel disease, requiring surgery for their condition. Bacterial DNA was extracted from the resected mucosal samples and bifidobacterial mucosa-associated microbiota was qualitatively and quantitatively determined by means of qualitative and quantitative PCR. RESULTS： Bifidobacteria were found in 100% of the samples from patients with diverticulitis or IBD and a 76% of those suffering colon cancer. The species B. Iongum and B. bifidum were the most widely found, followed by B. animalis, B. catenulatum and B. adolescentis. B. breve, B. dentium and B. angulatum were not detected in any sample. A significantly higher occurrence of B. Iongum was observed in patients with diverticulitis than in those with colon cancer or IBD （100%, 62% and 75%, respectively, P 〈 0.05）. Similar results were obtained for B, animalis （56%, 0% and 25%, P 〈 0.05）, while B. adolescentis was only found in the mucosa from patients with colon cancer （5 out of 21, 24%）. At the quantitative level, patients with colon cancer or IBD showed lower counts of total Bifidobacterium （4.94 and 5.91 vs 6.96 log Cells/sample, respectively, P 〈 0.05） and of the species B. longum （4.05 and 4.79 vs 6.76, P 〈 0.05） than those with diverticulitis.CONCLUSION： Aberrancies in mucosa associated microbiota are present in different intestinal diseases. This may indicate a role of the microbiota in the pathogenesis of these diseases.

Hypoxia-inducible factor 1 alpha and vascular endothelial growth factor overexpression in ischemic colitis

AIM: To examine the etiology and pathophysiology in human ischemic colitis from the viewpoint of ischemic factors such as hypoxia-inducible factor 1 alpha (HIF-1 alpha and vascular endothelial growth factor (VEGF). METHODS: Thirteen patients with ischemic colitis and 21 normal controls underwent colonoscopy. The follow-up colonoscopy was performed in 8 patients at 7 to 10 d after the occurrence of ischemic colitis. Biopsy samples were subjected to real-time RT-PCR and immunohistochemistry to detect the expression of HIF-1 alpha and VEGF. RESULTS: HIF-1 alpha and VEGF expression were found in the normal colon tissues by RT-PCR and immunohistochemistry. HIF-1 alpha and VEGF were overexpressed in the lesions of ischemic colitis. Overexpressed HIF-1 alpha and VEGF RNA quickly decreased to the normal level in the scar regions at 7 to 10 d after the occurrence of ischemic colitis. CONCLUSION: Constant expression of HIF-1 alpha and VEGF in normal human colon tissue suggested that HIF-1 alpha and VEGF play an important role in maintaining tissue integrity. We confirmed the ischemic crisis in ischemic colitis at the molecular level, demonstrating overexpression of HIF-1 alpha and VEGF in ischemic lesions. These ischemic factors may play an important role in the pathophysiology of ischemic colitis.

Functional dyspepsia and irritable bowel syndrome,are they different entities and does it matter?

A high prevalence of overlap between functional dyspepsia and irritable bowel syndrome has been consistently and universally reported. Recent studies demonstrating shared common pathophysiological disturbances including delayed gastric emptying and visceral hypersensitivity involving more than one region, suggest that these patients have a generalised rather than regional, disorder of the gut. Furthermore, a study of the natural history of dyspepsia suggests that with time, a substantial proportion will evolve into IBS. The recognition of IBS in dyspeptic patients has potentially profound therapeutic importance. It could help to reduce the risk of unnecessary cholecystectomy in IBS patients. The ability to appreciate the extent of involvement could allow us to address the disturbances more comprehensively, and thereby achieve greater patient satisfaction with their treatment.

Assessment of small intestinal bacterial overgrowth in uncomplicated acute diverticulitis of the colon

AIM: Small intestinal bacterial overgrowth (SIBO) maycontribute to the appearance of several gastrointestinal nonspecific symptoms. Acute diverticulitis is affected by some similar symptoms and bacterial colonic overgrowth. We assessed the prevalence of SIBO in acute uncomplicated diverticulitis and evaluated its influence on the clinical course of the disease.METHODS: We studied 90 consecutive patients (39 males, 51 females, mean age 67.2 years, range 32-91 years). Sixty-one patients (67.78%) and 29 patients (32.22%) were affected by constipation-or diarrhea-prevalent diverticulitis respectively. All subjects were investigated by lactulose H2-breath test at the entry and at the end of treatment. We also studied a control group of 20 healthy subjects (13 males, 7 females, mean age 53 years, range 22-71 years).RESULTS: Oro-cecal transit time (OCTT) was delayed in67/90 patients (74.44%) (range 115-210 min, mean 120 min). Fifty-three of ninety patients (58.88%) showed SIBO, while OCTT was normal in 23/90 patients (25, 56%). In the control group, the mean OCTT was 88.2 min (range 75-135 min). The difference between diverticulitic patients and healthy subjects was statistically significant (P＜0.01). OCTT was longer in constipation-prevalent disease than in diarrheaprevalent disease [180.7 min (range 150-210 min) vs 121 min (range 75-180 min) (P＜0.001)], but no difference in bacterial overgrowth was found between the two forms of diverticulitis.After treatment with rifaximin plus mesalazine for 10 d, followed by mesalazine alone for 8 wk, 70 patients (81.49%) were completely asymptomatic, while 16 patients (18.60%) showed only slight symptoms. Two patients (2.22%) had recurrence of diverticulitis, and two other patients (2.22%) were withdrawn from the study due to side-effects. Seventy-nine of eighty-six patients (91.86%) showed normal OCTT (range 75-105 min, mean 83 min), while OCTT was longer, but it was shorter in the remaining seven (8.14%) patients (range 105-115 min, mean of 110 min). SIBO was eradicated in all patients, while it persisted in one patient with recurrence of diverticulitis. CONCLUSION: SIBO affects most of the patients with acute diverticulitis. SIBO may worsen the symptoms of patients and prolong the clinical course of the disease, as confirmed in the case of persistence of SIBO and diverticulitis recurrence. In this case, we can hypothesize that bacteria from small bowel may re-colonize in the colon and provoke recurrence of symptoms.

Recent advances and remaining gaps in our knowledge of associations between gut microbiota and human health

The complex gut microbial flora harbored by individuals(microbiota) has long been proposed to contribute tointestinal health as well as disease. Pre-and probioticproducts aimed at improving health by modifyingmicrobiota composition have already become widelyavailable and acceptance of these products appearsto be on the rise. However, although required forthe development of effective microbiota basedinterventions, our basic understanding of microbiotavariation on a population level and its dynamics withinindividuals is still rudimentary. Powerful new parallelsequence technologies combined with other efficientmolecular microbiota analysis methods now allow forcomprehensive analysis of microbiota composition inlarge human populations. Recent fi ndings in the fi eldstrongly suggest that microbiota contributes to thedevelopment of obesity, atopic diseases, inflammatorybowel diseases and intestinal cancers. Through theongoing National Institutes of Health Roadmap 'HumanMicrobiome Project' and similar projects in other partsof the world, a large coordinated effort is currentlyunderway to study how microbiota can impact humanhealth. Translating findings from these studies intoeffective interventions that can improve health,possibly personalized based on an individuals existingmicrobiota, will be the task for the next decade(s).

Frequency of alcohol and smoking cessation counseling in hepatitis C patients among internists and gastroenterologists

Given the overwhelming evidence that both alcoho consumption and smoking accelerate the progression of hepatitis C virus(HCV)-induced liver disease we evaluated the frequency of alcohol and smoking counseling of patients with HCV-induced liver disease by their primary care internists and gastroenterologists.One hundred and twenty-three medical records of consecutive patients with HCV-induced liver disease referred by an internist to a gastroenterologist for its management were reviewed.Patient gender,race,history of and counseling against alcohol and tobacco use by a physician and a gastroenterologist were obtained A database was created using Microsoft Excel.There were 105 African-Americans,12 Caucasians and six patients of other races/ethnicities.Forty-six(37%)pa- tients were daily tobacco users and 34(28%)patients were daily alcohol consumers.There was a statistically significant difference in the frequencies of alcohol(P= 0.0002)and smoking cessation(P=0.0022)between gastroenterologists and internists.This study reveals that internists and gastroenterologists,alike,inadequately counsel patients with hepatitis C about tobacco and alcohol use.

Eosinophilic colitis

Eosinophilic colitis (EC) is a rare form of primary eosinophilic gastrointestinal disease with a bimodal peak of prevalence in neonates and young adults. EC remains a little understood condition in contrast to the increasingly recognized eosinophilic esophagitis. Clinical presentation of EC is highly variable according to mucosal, transmural, or serosal predominance of inflammation. EC has a broad differential diagnosis because colon tissue eosinophilia often occurs in parasitic infection, drug-induced allergic reactions, inflammatory bowel disease, and various connective tissue disorders, which require thorough searching for secondary causes that may be specifically treated with antibiotics or dietary and drug elimination. Like eosinophilic gastrointestinal disease involving other segments of the gastrointestinal tract, EC responds very well to steroids that may be spared by using antihistamines, leukotriene inhibitors and biologics.

Inflammatory bowel disease-and Barrett’s esophagus-associated neoplasia:the old,the new,and the persistent struggles

Early diagnosis of and adequate therapy for premalignant lesions in patients with inflammatory bowel disease(IBD)and Barrett’s esophagus(BE)has been shown to decrease mortality.Endoscopic examination with histologic evaluation of random and targeted biopsies remains the gold standard for early detection and adequate treatment of neoplasia in both these diseases.Although eventual patient management(including surveillance and treatment)depends upon a precise histologic assessment of the initial biopsy,accurately diagnosing and grading IBD-and BE-associated dysplasia is still considered challenging by many general as well as subspecialized pathologists.Additionally,there are continuing updates in the literature regarding the diagnosis,surveillance,and treatment of these disease entities.This comprehensive review discusses the cancer risk,detailed histopathological features,diagnostic challenges,and updates as well as the latest surveillance and treatment recommendations in IBD-and BE-associated dysplasia.

Variations in the medical treatment of inflammatory bowel disease among gastroenterologists

Background and aims:With expanding available treatment options and evolving understanding of the risks and benefits of medical therapies for inflammatory bowel disease(IBD),there is the possibility of significant variations in treatment and outcomes.Little is known about the variation in treatment between IBD specialists and other gastroenterology(GI)physicians.Evaluating possible variations is an important first step to help address standardized care and optimize treatment.We studied the differences in use of biologics and immunomodulators in the management of IBD patients at a tertiary care hospital between IBD-trained physicians and other gastroenterologists.Methods:A total of 325 IBD patients were included in the analysis.Of these,216 patients received care with an IBD physician and 109 had other GI/non-IBD physicians as their main caregivers.Results:The unadjusted use of immunomodulators(35.6%vs 16.5%,p¼0.001),biologics(45.8%vs 22.9%,p¼0.001)and dual therapy(biologics and immunomodulator)(14.4%vs 3.7%,p¼0.001)was significantly higher in the IBD-physician group.These differences in therapy between the two groups remained after adjusting for patient and disease characteristics.Conclusion:There are significant variations in the treatment of patients with IBD by GI physicians.The use of biologics and immunomodulators is higher in GI physicians with dedicated IBD interest and training.