Katya Gudis

High dose probiotic and prebiotic cotherapy for remission induction of active Crohn's disease

Background:  Clinical trials of probiotic treatment for Crohn’s disease (CD) have yielded conflicting results. This study assessed the clinical usefulness of combined probiotic and prebiotic therapy in the treatment of active CD.

A randomized controlled trial on the efficacy of synbiotic versus probiotic or prebiotic treatment to improve the quality of life in patients with ulcerative colitis.

OBJECTIVE Studies suggest that synbiotic therapy could prove more effective in the treatment of ulcerative colitis (UC) than therapies limited to probiotics or prebiotics. This study compared the effect of each of these therapies in the treatment of UC. METHODS One hundred twenty outpatients with UC were randomly sorted into three groups of 40 patients each for probiotic, prebiotic, or synbiotic therapy. The probiotic group ingested one daily capsule consisting of Bifidobacterium longum 2 x 10(9) colony-forming units and the prebiotic group ingested daily 8.0-g doses of psyllium. The synbiotic group underwent both treatments. All patients completed Inflammatory Bowel Disease Questionnaires (IBDQs) at the onset of the trial, at the 2-wk midpoint, and at the 4-wk end of the trial. Blood variables were also evaluated in a subset of 32 patients randomly selected from all groups and values were compared with IBDQ scores. RESULTS Thirty-one patients in the probiotic group, 31 in the prebiotic group, and 32 in the synbiotic group qualified for analyses. The remaining 26 patients had incomplete questionnaires. Total IBDQ scores improved within groups by the end of the trial (probiotics 162 to 169, NS; prebiotics 174 to 182, NS; synbiotics 168 to 176, P = 0.03). Individual scores improved as follows: probiotics, emotional function (P = 0.03); prebiotics, bowel function (P = 0.04); and synbiotics, systemic and social functions (P = 0.008 and P = 0.02). C-reactive protein decreased significantly only with synbiotic therapy (from 0.59 to 0.14 mg/dL, P = 0.04). There were no adverse events. CONCLUSION Patients with UC on synbiotic therapy experienced greater quality-of-life changes than patients on probiotic or prebiotic treatment. These data suggest that synbiotic therapy may have a synergistic effect in the treatment of UC.

Effect of Helicobacter pylori infection on ghrelin expression in human gastric mucosa.

OBJECTIVES:One of the counter-effects of Helicobacter pylori eradication therapy is subsequent obesity. Ghrelin is a recently discovered growth hormone releasing peptide. This endogenous secretagogue increases appetite and facilitates fat storage. The majority of circulating ghrelin is produced in the gastric mucosa. Therefore, we aimed at investigating changes in ghrelin immunoreactivity in gastric mucosa tissues of patients infected with H. pylori.METHODS:Sixty-one patients with H. pylori infection (25 cases each of duodenal and gastric ulcer, and 11 cases of gastritis) and 22 healthy controls without H. pylori infection were included in the study. H. pylori-infected patients received standard proton pump-based triple therapy followed by histological examination and 13C-urea breath test to confirm H. pylori eradication. H. pylori was eradicated in 50 out of 61 patients. Biopsy specimens were obtained from antrum and corpus before and 3 months following eradication. Ghrelin expression was evaluated immunohistochemically with an anti-ghrelin antibody, and the number of ghrelin-positive cells determined per 1 mm2 of the lamina propria mucosa.RESULTS:There was no relationship between ghrelin immunoreactivity and body weight or body mass index for healthy controls. The number of ghrelin-positive cells was significantly lower for H. pylori-infected patients than for healthy controls. However, the ghrelin-positive cell number increased significantly following H. pylori eradication without significant change in severity of atrophy.CONCLUSIONS:These data indicated that H. pylori infection affected ghrelin expression. After H. pylori eradication, gastric tissue ghrelin concentration increased significantly. This could lead to the increased appetite and weight gain seen following H. pylori eradication.

Prevention of nonsteroidal anti-inflammatory drug–induced small-intestinal injury by prostaglandin: a pilot randomized controlled trial evaluated by capsule endoscopy

BACKGROUND There is no known preventive agent against nonsteroidal anti-inflammatory drug (NSAID) induced small-intestinal injury. OBJECTIVE To evaluate by capsule endoscopy whether coadministration of prostaglandin (PG) can prevent small-intestinal damage induced by short-term NSAID treatment. DESIGN Single-blind, randomized, controlled trial. SETTING All procedures were performed at Nippon Medical School. SUBJECTS Thirty-four healthy male volunteers. METHODS All subjects were randomly assigned to 2 groups: an NSAID-control group, who underwent NSAID (diclofenac sodium, 25 mg 3 times daily) and omeprazole (20 mg once daily) treatment, and an NSAID-PG group, who received PG (misoprostol, 200 microg 3 times daily) in addition to the same NSAID-omeprazole treatment. Eligible subjects, 15 per group, underwent capsule endoscopy before and 14 days after treatment. MAIN OUTCOME MEASUREMENTS The number of mucosal breaks at capsule endoscopy. RESULTS NSAID treatment significantly increased the mean (SD) number of mucosal breaks per subject, from a basal level of 0.1 +/- 0.3 up to 2.9 +/- 6.3 lesions in the NSAID-control group (P = .012). In contrast, there was no significant change in the mean number of mucosal breaks before and after PG cotreatment (P = 0.42). Thus, the mean number of posttreatment mucosal breaks per subject was significantly higher in the NSAID-control group than in the NSAID-PG group (P = .028). There was a significant increase in the percentage of subjects in the NSAID-control group, with at least 1 mucosal break after treatment (from 6.7% to 53.3%), whereas there was no change in the incidence of mucosal breaks in the NSAID-PG group, which remained at 13.3%. (P = .002). LIMITATIONS Single-center, open-label study. CONCLUSIONS PG cotherapy reduced the incidence of small-intestinal lesions induced by a 2-week administration of diclofenac sodium.

Comparison of gastric emptying and plasma ghrelin levels in patients with functional dyspepsia and non-erosive reflux disease.

Background and Aims: The symptoms of postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS), the two subtypes of functional dyspepsia (FD) under the new Rome III classification, tend to overlap with those of non-erosive reflux disease (NERD). Plasma ghrelin levels have been associated with gastric motility; however, clinical studies have yet to examine this relationship among patients with PDS, EPS or NERD. Thus, this study aims to evaluate the correlation between gastric emptying and ghrelin levels as possible candidate factors for gastric motility in these diseases. Methods: One hundred and fifty-one patients presenting with typical symptoms of FD (EPS, n = 36; PDS, n = 76) or NERD (n = 39), and 20 healthy volunteers were enrolled. Gastric motility was evaluated with the Tmax value as a marker of gastric emptying using the 13C-acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms, and SRQ-D scores to determine depression status. We measured both acylated and des-acylated ghrelin levels by ELISA methods. Results: The Tmax value in PDS patients was significantly higher than in healthy volunteers. Acylated ghrelin levels were significantly lower in NERD and PDS patients than in healthy volunteers. Interestingly, there was significant correlation between the acylated ghrelin levels and Tmax value in PDS patients but not in EPS or NERD patients. Conclusion: Our results suggest that acylated ghrelin might play an important role in the pathophysiology of PDS patients through its effect on gastric emptying.

Diagnostic yield of double-balloon endoscopy in patients with obscure GI bleeding.

BACKGROUND Double-balloon endoscopy (DBE) is a new method that allows visualization, tissue sampling, and therapeutic intervention of a variety of pathologies throughout the small-intestinal tract. OBJECTIVE In the present study, we evaluated the diagnostic yield of DBE and its impact on the final diagnosis, treatment, and clinical outcome of patients with obscure GI bleeding (OGIB). DESIGN AND SETTING A hospital-based cross-sectional, follow-up study. PATIENTS We studied 108 consecutive patients (66 men and 42 women) referred to our hospital from July 2003 to February 2007 for the evaluation of OGIB: 13 patients with overt-ongoing bleeding, 76 with overt-previous bleeding, and 19 with occult OGIB. MAIN OUTCOME MEASUREMENTS Diagnostic yield, a final diagnosis, treatment, and clinical outcome were all analyzed in each group. RESULTS DBE diagnostic rates for patients with overt-ongoing, overt-previous, and occult bleeding were 100.0%, 48.4% and 42.1%, respectively. The difference in diagnostic yields between the overt-ongoing group and the 2 other groups was statistically significant (P < .005). The most common sources of bleeding were ulcers and tumor lesions. Small-intestinal lesions were identified in 52 of 108 patients; of which 36 patients (69.2%) were biopsied and 49 patients (94.2%) received treatment. Eight patients (7.4%) had recurrent bleeding during the mean follow-up period of 28.5 months. Sensitivity, specificity, and positive and negative predictive values of DBE in the diagnoses of small-intestinal lesions in patients with OGIB were 92.7%, 96.4%, 98.1%, and 87.1%, respectively. No serious complications were encountered. CONCLUSIONS DBE was proven to be a very useful diagnostic tool and had a therapeutic impact in the majority of patients with OGIB. The best candidates for the procedure were patients with overt-ongoing bleeding.

Migration of eosinophils and CCR2-/CD68-double positive cells into the duodenal mucosa of patients with postinfectious functional dyspepsia.

OBJECTIVES:Recent studies have shown that postinfectious functional dyspepsia (FD) symptoms may persist after elimination of gastrointestinal (GI) infection as well as postinfectious irritable bowel syndrome accompanying colonic inflammation. However, it is unclear whether intestinal chronic inflammation can contribute to clinical symptoms of certain FD patients such as postinfectious FD. To determine the relationship between local inflammation of the duodenum and clinical symptoms, we evaluated the infiltration of several phenotypes of duodenal inflammatory cells as well as gastric motility using 13C urea breath test in postinfectious FD patients.METHODS:We enrolled 136 consecutive patients diagnosed with FD according to Rome III criteria, and 20 healthy controls, after upper GI endoscopy. Gastric motility was evaluated by gastric emptying time (T-max) using the 13C-acetate breath test. Upper abdominal symptoms including epigastric pain, epigastric burning, postprandial fullness, abdominal distension, and early satiety were assessed by questionnaire scores. We obtained biopsy specimens from the stomach and duodenum during upper GI endoscopy. Histological gastritis and duodenitis were assessed as mild, moderate, or severe according to previously described criteria. Characteristics of inflammatory cells and neuroendocrine cells were determined immunohistochemically with antibodies to CD3, CD68, CCR2, Vdelta1 TCR, and serotonin.RESULTS:Endoscopic duodenitis was observed in only 5.7% of postinfectious FD patients. However, the rates of histological duodenitis in duodenal biopsies of postinfectious FD patients were 17% for mild, 26% for moderate, and 57% for severe grades of duodenitis. The degree of histological duodenitis of postinfectious FD patients was significantly greater than that of healthy volunteers. There was a significant correlation between epigastric burning and the degree of duodenitis in postinfectious FD patients. There was no significant difference in histological duodenitis and T-max value in the postinfectious FD patients with or without Helicobacter pylori infection. In addition, CD68-positive cell number in postinfectious FD patients was significantly increased compared with the numbers in subjects with epigastric pain syndrome or postprandial distress syndrome and in healthy volunteers. CCR2-/CD68-double positive cell number in postinfectious FD patients was significantly (P=0.009) increased compared with those in healthy volunteers.CONCLUSIONS:Migration of inflammatory cells, in particular, duodenal CCR2-positive macrophages, may have an important function in the pathophysiology of postinfectious FD patients.

Distribution of small intestinal mucosal injuries as a result of NSAID administration.

Eur J Clin Invest 2010; 40 (6): 504–510

Helicobacter pylori infection increases the risk of colorectal adenoma and adenocarcinoma, especially in women

BackgroundRecent reports suggest that Helicobacter pylori infection can potentially increase the risk of colorectal cancer. The purpose of this study was to assess the association between H. pylori infection and the risk of colorectal adenoma and adenocarcinoma, and to evaluate any differences on the basis of sex.MethodsThe subjects were 669 (40- to 80-year-old) patients who underwent both barium enema examination and total colonoscopy, and who were evaluated for H. pylori infection by 13C-urea breath test, urease test, or histological diagnosis of biopsied gastric specimens. There were 142 H. pylori-negative and 527-positive patients. The odds ratios (ORs) for H. pylori-positive patients with colorectal adenoma and adenocarcinoma, and for tumor patients with either adenoma or adenocarcinoma were calculated.ResultsAmong the H. pylori-negative patients, there were 52 patients without tumor, 63 with adenoma, 27 with adenocarcinoma, and 90 with tumor. Among the H. pylori-positive patients, there were 136, 264, 127, and 391 patients respectively. Pooling all subjects, those infected with H. pylori had a significantly increased OR for adenoma, adenocarcinoma, or tumor, compared to H. pylori-free patients (OR, 1.60, 1.80, and 1.66, respectively). For female H. pylori-positive subjects, the risk of having adenocarcinoma or tumor was significantly higher than that for their H. pylori-free counterparts, while for male H. pylori-positive and -negative subjects, there was no such significant difference.ConclusionsThe results therefore suggest that, in patients aged 40–80 years, H. pylori infection increased the risk of colorectal adenoma and adenocarcinoma, with significantly higher risks for female patients.

The Role of Cyclooxygenase in Gastric Mucosal Protection

COX-1 and COX-2 are two cyclooxygenase enzymes responsible for prostanoid production. COX-2 is expressed in inflammatory cells and fibroblasts of the gastric mucosa, and through the production of various growth factors including hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF), plays a key role in the tissue repair process. Aspirin induces and acetylates COX-2 to produce 15-(R)-epi-lipoxinA4, an anti-inflammatory mediator thought to protect the gastric mucosa against aspirin-induced injury. Recently, three different PGE synthases have been identified, that convert COX-2 metabolites into PGE2. mPGE synthase (mPGES)-1 has been shown to be inducible, and to colocalize with COX-2 in fibroblasts and macrophages infiltrating the gastric ulcer bed. cPGES and mPGES-2 have been found expressed in normal gastric mucosa, with no change in expression levels seen in gastritis or gastric ulcer tissue. Finally, this review discusses the role of these enzymes in the pathophysiology of the gastric mucosa, as well as the biologcal significance of their inhibition.