Diarrhea-predominant Irritable Bowel Syndrome Patients Research Articles

Effect of Probiotic Administration Immediately and 1 Month after Colonoscopy in Diarrhea-predominant Irritable Bowel Syndrome Patients.

Background:Irritable bowel syndrome (IBS) is one of the most common disorders among young adults. Various studies have demonstrated that the use of probiotics can reduce the overall symptom of IBS, and thus, our aim was to evaluate the efficacy of probiotic products in the reduction of IBS syndrome after colonoscopy.Materials and Methods:Our patients were divided among three groups, including immediate probiotic users, start use of probiotics 1 month after colonoscopy, and placebo group. All the patients were interviewed for having common IBS symptoms (stool consistency and frequency, gas, abdominal pain, and flatulence) at baseline, 3rd month of follow-up, and 6th month of follow-up.Results:The mean reduction in abdominal pain was 3.05 ± 1.21, 3.86 ± 0.94, and 3.82 ± 0.63 in the control group, immediate probiotic users, and 1 month after colonoscopy, respectively (P < 0.001). The symptoms of the disease, such as stool consistency, the frequency of defecation, and flatulence (except gas) in the first quarter, in the two treatment groups were significantly improved more than in the control group (P < 0.05). In contrast, the frequency of defecation was not significantly different in the treatment group receiving the probiotics month after colonoscopy compared to the placebo users (P > 0.05).Conclusion:According to our results, the use of probiotics had the beneficial effect on IBS symptoms. Furthermore, it can be said that reductions in symptoms and pain in the two treatment groups were not significantly different, but after 6 months of treatment, the effect of probiotics in patients who immediately use it after colonoscopy was more visible and more stable.

Claudin-2 expression is upregulated in the ileum of diarrhea predominant irritable bowel syndrome patients.

Intestinal epithelial barrier function is impaired in irritable bowel syndrome patients. Claudins are highly expressed in cells with tight junctions and are involved in the intestinal epithelial barrier function. The expression pattern of tight junction proteins in diarrhea-predominant irritable bowel syndrome have not been fully elucidated. We therefore recruited 17 diarrhea-predominant irritable bowel syndrome patients and 20 healthy controls. The expression of the tight junction-related proteins was examined in the ileal, cecal, and rectal mucosa of diarrhea-predominant irritable bowel syndrome patients using real-time PCR and immunofluorescence. Claudin-2 expression was high in the ileum of diarrhea-predominant irritable bowel syndrome patients. Claudin-2 expression was the same in cecum and rectal mucosa of control and diarrhea-predominant irritable bowel syndrome patients. Similarly, the expression of clauidn-1, claudin-7, JAM-A, occludin, and ZO-1 in the ileal, cecal, and rectal mucosa did not change between control and diarrhea-predominant irritable bowel syndrome samples. Infiltration of eosinophil and mast cells in the mucosa of ileum, cecum and rectum was evaluated using immunohistochemical staining and was not affected by diarrhea-predominant irritable bowel syndrome. Claudin-2 was expressed on the apical side of villi and crypts of ileal mucosal epithelial cells. Clauidn-2 expression is upregulated in diarrhea-predominant irritable bowel syndrome patients and may contribute to the pathogenesis of this condition.

The correlation study between the changes of intestinal mucosa predominant bacteria and Toll-like receptor 2, Toll-like receptor 4 gene expressions in diarrhea-predominant irritable bowel syndrome patients

Based on high throughput sequencing and PCR detection technology, this study has found out that intestinal microbial diversity was impaired and the quantities of two main bacteria flora (Bacteroidetes and Clostridium) were significantly reduced in patients with diarrhea-predominant irritable bowel syndrome (D-IBS). Meanwhile mucosal expression of toll-like receptor (TLR) 2 and TLR4 were significantly enhanced, which was inversely correlated with the reduction of Bacteroidetes and Clostridium. Thus, it suggests that D-IBS may be associated with TLR signal transduction triggered by the intestinal dysbacteriosis.

Clinical features of irritable bowel syndrome with small intestinal bacterial overgrowth and a preliminary study of effectiveness of Rifaximin

To investigate the prevalence and clinical features of small intestinal bacterial overgrowth (SIBO) in diarrhea-predominant irritable bowel syndrome (IBS-D) patients detected by hydrogen and methane in lactulose breath test (LBT), and to study the effects of rifaximin in IBS-D patients. Consecutive patients with IBS-D who met Rome Ⅲ criteria, and gender- and age-matched healthy volunteers were enrolled from March 2015 to January 2016 in Peking University Third Hospital. All the ISB-D patients underwent LBT to detect the prevalence of SIBO. The clinical and LBT features of IBS with SIBO (IBS-P group) and without SIBO (IBS-N group) were analyzed. The effects of rifaximin therapy (0.4 g, twice per day for 4 weeks) in IBS-D patients were evaluated by comparing changes in clinical features and LBT results after treatment. (1) Eighty-four IBS-D patients and 22 healthy controls were enrolled. The prevalence of SIBO in IBS-D patients was 41.67% (35/84), with 27 (77.14%) only hydrogen-positive, 5 (14.29%) methane-positive, and 3 (8.57%) both methane- and hydrogen-positive. (2) The body mass index (BMI) in the IBS-P group was lower than in the IBS-N group [(21.61±0.57) vs (23.44±0.54) kg/m(2,) P<0.05], the maximum stool frequency was also less than in the IBS-N group [(3.85±0.23) vs (4.88±0.35) times/day, P<0.05]. (3) No significant difference was found in oro-cecal transit time (OCTT) among IBS-P, IBS-N and healthy controls. The hydrogen concentration in small intestinal and colonic sections in breath of the IBS-P group was higher than that of both healthy controls and the IBS-N group, while methane concentration in small intestinal and colonic sections (160 min) was higher than that of the IBS-N group (all P<0.05). (4) There was no linear relationship between mean hydrogen and methane concentrations in LBT among the IBS-P, the IBS-N and healthy control groups (all r<0.35, P>0.05). (5) Totally 13 IBS-P patients received rifaximin therapy, in whom the symptoms of abdomen pain, bloating, fecal consistency, stool frequency, and stool satisfactory were significantly improved after treatment (all P<0.05); 8 IBS-N patients received rifaximin therapy, in whom fecal consistency, stool frequency, and satisfactory were significantly improved (all P<0.05). (6) And 5/13 of the IBS-P patients receiving rifaximin presented negative LBT results after rifaximin therapy, with lower hydrogen concentration at all the time points, especially in colonic section (120 min) [(34.54±7.32) ×10(-6) vs (52.23±9.40) ×10(-6,) P<0.05] and lower methane concentration especially in small intestinal section (80 min) [(8.54±0.95) ×10(-6) vs (11.31±0.94) ×10(-6,) P<0.05]. About 41.67% of the IBS-D patients meeting Rome Ⅲ criteria have SIBO, which can be better screened by combining hydrogen and methane in LBT compared with only hydrogen in LBT. SIBO can affect nutritional status in IBS-D patients. Rifaximin can improve the systematic symptoms of IBS-D patients with SIBO, also reduce hydrogen and methane concentration in breath, while only improving diarrhea in IBS-D patients without SIBO. Some differences in gut microbiota may exist between IBS-D with and without SIBO.

The Colonic Tissue Levels of TLR2, TLR4 and Nitric Oxide in Patients with Irritable Bowel Syndrome

Objective Irritable bowel syndrome (IBS) is a highly prevalent and debilitating functional disorder. The toll-like receptors (TLRs) are a family of pathogen-recognition receptors in the innate immune system. In the present study we aimed to investigate the TLR2, TLR4 and nitric oxide (NO) levels in patients with IBS. Methods Fifty-one IBS patients and 15 healthy controls were included in the present study. Colonic tissue levels of TLR2, TLR4 and NO were detected using an enzyme-linked immunosorbent assays (ELISA) and through biochemical methods. Results The colonic tissue levels of TLR4 and NO were significantly higher in IBS patients than in healthy controls. A subgroup analysis, which was based on the presence of diarrhea and constipation, showed that TLR2 levels were significantly higher among individuals with diarrhea-predominant IBS than among constipation-predominant IBS patients and healthy controls. The TLR4 levels were significantly higher in the diarrhea-predominant IBS patients and constipation-predominant IBS patients than in comparison healthy controls. The colonic tissue levels of NO were higher in the constipation-predominant IBS patients than in the diarrhea-predominant IBS patients and healthy controls. Conclusion In the present study we found that the colonic tissue levels of TLR and NO were elevated in IBS patients. Our results support the presence of a degree of immune dysregulation and oxidative stress in patients with IBS.

Effect of TongXie-YaoFang on Cl(-) and HCO3 (-) Transport in Diarrhea-Predominant Irritable Bowel Syndrome Rats.

TongXie-YaoFang (TXYF) can effectively alleviate the symptoms of diarrhea-predominant irritable bowel syndrome (D-IBS) patients. However, the curative mechanism has not been fully clarified. The study was designed to investigate the effect of TXYF on the colonic ion transport induced by serotonin (5-HT) in D-IBS rats. A method of multiple stress (neonatal maternal separation (NMS) combined with restraint stress (RS)) was used to induce the D-IBS model. The model rats were randomly divided into two groups: NMS + RS group and TXYF-formula group, and the normal control (no handling) rats were classified as NH group. In the NMS + RS group, the change of short-circuit current (ΔI sc) induced by 5-HT was lower than that in the NH and TXYF-formula groups. After removing of the extracellular Cl− or HCO3 − or basolateral Na+ or blocking the cystic fibrosis transmembrane conductance regulator (CFTR), Na+-K+-2Cl− cotransporter (NKCC), Na+-HCO3 − cotransporter, Cl−/HCO3 − exchanger, K+ channel, or Na+/K+-ATPase, respectively, there was no difference in 5-HT-induced ΔI sc among the three groups. These data suggest that TXYF can regulate 5-HT-induced Cl− and HCO3 − secretion, possibly mediated by the combined action of CFTR, NKCC, Na+-HCO3 − cotransporter, Cl−/HCO3 − exchanger, K+ channel, and Na+/K+-ATPase.

Increased serum levels of lipopolysaccharide and antiflagellin antibodies in patients with diarrhea-predominant irritable bowel syndrome.

Innate immune responses to conserved microbial products such as lipopolysaccharide (LPS) and flagellin are likely important in microbial-host interactions and intestinal homeostasis. We hypothesized that bacterial translocation and activation of mucosal immunity against common microbial antigens might be involved in the development of irritable bowel syndrome (IBS). We therefore compared serum levels of LPS, soluble CD14 (sCD14), and flagellin antibodies between patients with different subtypes of IBS and healthy controls. We analyzed serum obtained from 88 patients (74 females) aged 19(43)-73 years and 106 healthy volunteers (77 females) aged 19(38)-62 years. Diarrhea-predominant IBS (D-IBS) was present in 32 patients (36%), 23 patients (26%) had constipation-predominant IBS (C-IBS), and 33 patients (38%) had A-IBS. We used ELISA for sCD14 and antiflagellin immunoglobulin G and limulus amebocyte assay for LPS. Abdominal symptoms and psychiatric comorbidities were assessed using validated questionnaires. We found a significantly higher serum level of LPS in patients with D-IBS compared to controls (p = 0.0155). The level of antibodies to flagellin was higher in patients with IBS than in controls (mainly driven by higher levels in D-IBS, p = 0.0018). The levels of sCD14 were lower in D-IBS patients compared to controls (p = 0.0498). We found a weak, but significant correlation between the levels of antiflagellin antibodies and anxiety among IBS patients (ρ = 0.38; p = 0.0045). Our results support the concept that immune reactivity to luminal antigens may have a role in the development of D-IBS. The serum level of antiflagellin antibodies was found to correlate with patients' self-reported anxiety score.

OC-067 A single-blinded study evaluating the effects of a gluten-free diet in diarrhoea-predominant irritable bowel syndrome

Introduction Gluten has been shown to alter bowel barrier function in patients with diarrhoea-predominant irritable bowel syndrome (D-IBS), particularly those who are HLA-DQ positive. Aims To assess the clinical response to a gluten-free diet (GFD) in D-IBS patients previously naive to the effects of gluten and blinded to HLA-DQ status. Method Between May 2012 to December 2014 we enrolled 48 D-IBS patients (24 HLA-DQ positive and 24 HLA-DQ negative) to undertake a six-week GFD. Patients commenced a GFD after seeing an expert dietitian. Both patients and dietitian were blinded to HLA-DQ status. Questionnaires were self-completed at baseline and at week 6. The primary end-point was change in IBS-symptom severity score (IBS-SSS), with a 50 point reduction conferring clinical benefit. Secondary end-points were change in IBS-quality of life (IBS-QOL), short form-36 (SF-36), hospital anxiety and depression score (HADS) and fatigue impact score (FIS). Results Data from 41 patients (74.4% women, mean-age 40.3 yrs) was available for per protocol analysis. Of these, 21 were HLA-DQ positive and 20 HLA-DQ negative; baseline characteristics were similar other than worse physical-fatigue (0.04) and vitality (0.05) in the HLA-DQ positive group. Overall, a GFD reduced IBS-SSS ≥50 points in 76% (n = 31). In fact, the mean-total IBS-SSS decreased from 286 to 131 (change –155, p Conclusion A GFD is a therapeutic option for the management of D-IBS. A clinical improvement was seen in 76% of patients undertaking a six-week GFD, with 61% opting to continue with a GFD for the foreseeable future. The pathophysiological mechanism may differ according to HLA-DQ status. Disclosure of interest None Declared.

Small intestinal bacterial overgrowth as an uncommon cause of false positive lactose hydrogen breath test among patients with diarrhea-predominant irritable bowel syndrome in Asia.

It has been reported that small intestinal bacterial overgrowth (SIBO) may lead to false positive diagnoses of lactose malabsorption (LM) in irritable bowel syndrome patients. The aim of this study was to determine the influence of SIBO on lactose hydrogen breath test (HBT) results in these patients. Diarrhea-predominant irritable bowel syndrome patients with abnormal lactose HBTs ingested a test meal containing (99m) Tc and lactose. The location of the test meal and the breath levels of hydrogen were recorded simultaneously by scintigraphic scanning and lactose HBT, respectively. The increase in hydrogen concentration was not considered to be caused by SIBO if ≥ 10% of (99m) Tc accumulated in the cecal region at the time or before of abnormal lactose HBT. LM was present in 84% (31/37) of irritable bowel syndrome patients. Twenty of these patients agreed to measurement of oro-cecal transit time. Only three patients (15%) with abnormal lactose HBT might have had SIBO. The median oro-cecal transit time between LM and lactose intolerance patients were 75 min and 45 min, respectively (Z=2.545, P=0.011). Most of irritable bowel syndrome patients with an abnormal lactose HBT had LM. SIBO had little impact on the interpretation of lactose HBTs. The patients with lactose intolerance had faster small intestinal transit than LM patients.

Mo2033 Marked Elevation in Mucosal Proinflammatory PGE2 Is Responsible for Pain in Diarrhea Predominant IBS (IBS-D) Patients

Background: Patients with irritable bowel syndrome (IBS) suffer from abdominal pain and associated constipation, diarrhea, and bloating. Some IBS patients (~35%) have visceral hypersensitivity to noxious experimental stimuli (e.g., colonic distension). We previously reported that colonic NMDA receptor signaling in IBS patients may be an underlying mechanism leading to visceral hypersensitivity that is reversed with Dextromethorphan (J Pain 2012;13:901-9). The current study was performed to determine if down regulation of in vivo NMDA receptor signaling via upregulation of miR-23a using miRNA mimics reverses visceral hypersensitivity in an IBS animal model. Methods: Male rats (n=12) received onehour water avoidance (WA) stress per day, for 10 consecutive days to induce visceral hypersensitivity as measured by colonic distension using a barostat. Intrathecal injection of miR-23a mimics (n=6 rats) or miRNA control (n=6 rats) was then performed and visceral hypersensitivity was measured 7 days later following injections. Following colonic barostat testing, all rats were sacrificed to measure colonic NMDA receptors and miR-23a expression using fluorescence in situ hybridization (FISH) using tyramide signal amplification (TSA) technology. Results: Rats treated with intrathecal injection of miR-23a mimics had decreased visceral hypersensitivity compared to rats that received intrathecal control miRNA (p<0.01). There was a significant increase in colonic miR-23a expression and a decrease in NMDA receptor signaling in rats that received miR-23a mimcs that correlated with decreased visceral hypersensitivity.Conclusion:Down regulation of NMDA receptor signaling through augmentation of miR-23a reverses visceral hypersensitivity in WA rats. Aberrant expression of key miRNAs dysregulate downstream targets such as NMDA receptors which contribute to visceral hypersensitivity in IBS patients. This data suggests that miR-23a could be a new therapeutic target for attenuating visceral hypersensitivity in IBS patients. Work supported by NIH grant (R01DK099052).

Clinical pilot study: efficacy of triple antibiotic therapy in Blastocystis positive irritable bowel syndrome patients.

BackgroundBlastocystis species are common human enteric parasites. Carriage has been linked to Irritable Bowel Syndrome (IBS). Treatment of Blastocystis spp. with antimicrobials is problematic and insensitive diagnostic methods and re-infection complicate assessment of eradication. We investigated whether triple antibiotic therapy comprising diloxanide furoate, trimethoprim/sulfamethoxazole and secnidazole (TAB) given to diarrhoea-predominant IBS (D-IBS) patients positive for Blastocystis would achieve eradication.MethodsIn a longitudinal, prospective case study 10 D-IBS Blastocystis-positive patients took 14 days of diloxanide furoate 500 mg thrice daily, trimethoprim/sulfamethoxazole 160/80 mg twice daily and secnidazole 400 mg thrice daily. Faecal specimens were collected at baseline, day 15 and 4 weeks after completion of TAB. Specimens were analysed using faecal smear, culture and polymerase chain reaction (PCR) of the 16 SSU rRNA. Patients kept a concurrent clinical diary.ResultsSix (60%) patients cleared Blastocystis spp. after TAB, including three who had failed previous therapy. Subtypes detected were ST3 (60%), ST4 (40%), ST1 (20%) and ST7, 8 (10%); four patients had mixed ST infections. Serum immunoglobulin A (IgA) levels were low in 40% of patients. Higher rates of Blastocystis clearance were observed in patients symptomatic for less than a year (Mann–Whitney, p = 0.032, 95% confidence) with no associations found with age, previous antibiotic therapy, faecal parasite load, ST, IgA level or clinical improvement.ConclusionsClearance of Blastocystis spp. was achieved with TAB in 60% of D-IBS patients, an improvement over conventional monotherapy. Higher clearance rates are needed to facilitate investigation of the relevance of this parasite in clinically heterogenous IBS.

Effects of Chili Treatment on Gastrointestinal and Rectal Sensation in Diarrhea-predominant Irritable Bowel Syndrome: A Randomized, Double-blinded, Crossover Study.

Background/AimsWhether, chronic chili ingestion can desensitize transient receptor potential vanilloid type 1 receptors in gastrointestinal (GI) tract leading to decrease GI symptoms and sensation in diarrhea-predominant irritable bowel syndrome (IBS-D) patients has not been well explored. The aim of this study was to determine the effects of 6-week chili treatment on postprandial GI symptoms and rectal sensation in response to balloon distention in IBS-D patients.MethodsSixteen IBS-D patients received placebo or chili capsules before meals 3 times/day for 6 weeks in a randomized, double-blinded, crossover fashion with 4-week washout period. Postprandial GI symptoms were evaluated. All patients underwent a rectal barostat study to evaluate rectal sensory threshold at the end of each treatment.ResultsThe maximum postprandial abdominal burning scores were similar between both treatments at baseline (1.4 [0.0–2.0] vs. 1.1 [0.0–2.8], P > 0.05) but were significantly decreased after chili (0.0 [0.0–0.5] vs. 0.3 [0.0–1.6], P < 0.05) at the end of treatment. The chili treatment significantly increased sensory threshold for the first rectal sensation (median [interquartile range]:16 [12–16] mmHg vs. 8 [8–16] mmHg, P < 0.05) however, there was no significant effect on rectal compliance (7.3 ± 1.0 vs. 7.1 ± 1.8 mL/mmHg). Other postprandial GI symptoms did not vary significantly between both treatments at baseline and the end of treatment.ConclusionsIn IBS-D patients, 6-week chili ingestion significantly decreased postprandial abdominal burning and increased the rectal sensory threshold. These findings suggest a desensitization effect of chili ingestion on transient receptor potential vanilloid type 1 receptors in the proximal gut and rectum.

Mast Cells in Irritable Bowel Syndrome and Ulcerative Colitis: Function Not Numbers Is What Makes All the Difference

Data obtained from animal and human studies support the existence of mast cells (MC) in the gastrointestinal (GI) tract, where they are considered important for the control of luminal parasites and possibly other microorganisms. MC are also implicated in food allergies, GI inflammation, and functional GI diseases, including irritable bowel syndrome (IBS) [1]. MC density may be increased in inflammatory bowel disease (IBD) and IBS, although such studies have yielded variable and sometimes contradictory results, likely due to methodological problems such as sampling issues, poorly characterized MC identification methodology, and lack of adequate documentation of disease correlates. There is no question that MC numbers are likely to be easier to identify and count in lesional areas as they may be present in IBD. MC density in the terminal ileum had previously been reported to be significantly increased in patients with IBS, even though MC abundance only correlated weakly with IBS symptoms, and, in some cases, a decreased density of colonic c-kit-positive in IgEor IgG-stained MC, was reported [2], even though IgEor IgG-staining is not an index of MC activation. In the paper by Choi et al. [3] published in this issue of Digestive Diseases and Sciences, the authors analyzed intestinal MC density in: (a) diverse patient cohorts, including diarrhea predominant-IBS (D-IBS), ulcerative colitis (UC) in remission, mild UC, and in healthy controls; (b) random colonic biopsies; (c) different colonic segments; and (d) mucosal MC and lamina propria/intra-epithelial T lymphocytes. The results are important because MC number was significantly increased in 97.6 % of D-IBS patients, intra-epithelial lymphocytes (IEL) were increased in 92.8 %, and lamina propria lymphocytes (LPL) were increased in 81.9 %. Moreover, even though the numbers of immune cells were even higher in some post-infectious (PI)-IBS patients, the remaining D-IBS patients had a significantly higher number of these cells compared with controls. Immunochemically identified were tryptase-positive MC and CD3-positive T cells (and not for all lymphocytes, as the authors stated). All publications to date, including the one by Choi et al. [3], did not report MC activation, which, according to some, is more important than actual numbers [4]. For instance, tryptase staining underestimates the number of degranulated MC, since released secretory granule tryptase does not stain. One way to identify degranulated MC is to stain for c-kit (CD117), the surface MC receptor for stem cell factor. Nevertheless, since mediator secretion can also occur without degranulation [5], MC activation can best be identified either by ultrastructural appearance T. C. Theoharides (&) Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA e-mail: theoharis.theoharides@tufts.edu

Clinical pilot study: efficacy of triple antibiotic therapy in

Blastocystis species are common human enteric parasites. Carriage has been linked to Irritable Bowel Syndrome (IBS). Treatment of Blastocystis spp. with antimicrobials is problematic and insensitive diagnostic methods and re-infection complicate assessment of eradication. We investigated whether triple antibiotic therapy comprising diloxanide furoate, trimethoprim/sulfamethoxazole and secnidazole (TAB) given to diarrhoea-predominant IBS (D-IBS) patients positive for Blastocystis would achieve eradication. In a longitudinal, prospective case study 10 D-IBS Blastocystis-positive patients took 14 days of diloxanide furoate 500 mg thrice daily, trimethoprim/sulfamethoxazole 160/80 mg twice daily and secnidazole 400 mg thrice daily. Faecal specimens were collected at baseline, day 15 and 4 weeks after completion of TAB. Specimens were analysed using faecal smear, culture and polymerase chain reaction (PCR) of the 16 SSU rRNA. Patients kept a concurrent clinical diary. Six (60%) patients cleared Blastocystis spp. after TAB, including three who had failed previous therapy. Subtypes detected were ST3 (60%), ST4 (40%), ST1 (20%) and ST7, 8 (10%); four patients had mixed ST infections. Serum immunoglobulin A (IgA) levels were low in 40% of patients. Higher rates of Blastocystis clearance were observed in patients symptomatic for less than a year (Mann-Whitney, p?=?0.032, 95% confidence) with no associations found with age, previous antibiotic therapy, faecal parasite load, ST, IgA level or clinical improvement. Clearance of Blastocystis spp. was achieved with TAB in 60% of D-IBS patients, an improvement over conventional monotherapy. Higher clearance rates are needed to facilitate investigation of the relevance of this parasite in clinically heterogenous IBS.

Sensitization of Peripheral Sensory Nerves by Mediators From Colonic Biopsies of Diarrhea-Predominant Irritable Bowel Syndrome Patients: A Role for PAR2

This study examined whether mediators from biopsies of human irritable bowel syndrome (IBS) colons alter intrinsic excitability of colonic nociceptive dorsal root ganglion (DRG) neurons by a protease activated receptor 2 (PAR2)-mediated mechanism. Colonic mucosal biopsies from IBS patients with constipation (IBS-C) or diarrhea (IBS-D) and from healthy controls were incubated in medium, and supernatants were collected. Small-diameter mouse colonic DRG neurons were incubated in supernatants overnight and perforated patch current-clamp recordings obtained. Measurements of rheobase and action potential discharge at twice rheobase were compared between IBS and controls to assess differences in intrinsic excitability. Supernatants from IBS-D patients elicited a marked increase in neuronal excitability compared with controls. These changes were consistent among individual patients but the relative contribution of rheobase and action potential discharge varied. In contrast, no differences in neuronal excitability were seen with IBS-C patient supernatants. The increased excitability seen with IBS-D supernatant was not observed in PAR2 knockout mice. A cysteine protease inhibitor, which had no effect on the pronociceptive actions of a serine protease, inhibited the proexcitatory actions of IBS-D supernatant. Soluble mediators from colonic biopsies from IBS-D but not IBS-C patients sensitized colonic nociceptive DRG neurons, suggesting differences between these two groups. PAR2 signaling plays a role in this action and this protease signaling pathway could provide novel biomarkers and therapeutic targets for treatment.

Association between diarrhea-predominant irritable bowel syndrome and HTR3A, HTR3E gene polymorphism in Yangzhou,Jiangsu province, China

To investigate the relationship between diarrhea-predominant irritable bowel syndrome (D-IBS) and HTR3A, HTR3E gene polymorphism in Yangzhou,Jiangsu province. Polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism (RFLP)technique were used to detect the 5'-UTR variant c.-42C > T of HTR3A and 3'-UTR variant c. ∗ 76G > A of HTR3E on 300 healthy subjects and 450 patients with D-IBS. There was significant difference noticed between the D-IBS patients and the controls in the genotype of c.-42C > T sites (P<0.05), while the frequency of T allele was significantly higher in both female and male patients than that in the controls (P < 0.05). The frequencies of G/A genotype and A allele of c. ∗ 76G > A sites were significantly higher in the female-patient group than that in the controls (P < 0.05), however, there was no significant difference between those male patients and controls(P > 0.05). When comparing to the CC genotype of rs1062613 site and GG genotype of rs 62625044 site, the TT and GA genotype were closely related to the D-IBS, with the risk coefficients as 0.29 (95% CI:0.14-0.61)and 0.62 (95% CI:0.39-0.99), with statistically significant differences. T allele and GA genotype might respectively serve as the predisposing factors of D-IBS and on the female D-IBS patients.

Su2034 Diagnosis of Small Intestinal Bacterial Overgrowth by Lactulose Hydrogen Breath Test With Scintigraphic Oro-Caecal Transit Test: Methodological Validation of Diagnostic Criteria in Healthy Controls and Patients With Diarrhea Predominant Irritable Bowel Syndrome

INTRODUCTION: The prevalence of small intestinal bacterial overgrowth (SIBO) in irritable bowel syndrome (IBS) patients remains contentious due to continuing uncertainty regarding diagnostic methodology. The lactulose hydrogen breath test (LHBT) is used to detect SIBO; however, recent papers have suggested that the results are confounded by wide variation of oro-caecal transit time. Combination with an independent, scintigraphic assessment of oro-cecal transit time (SOCTT) may address this problem with SIBO diagnosed when there is a rise in breath hydrogen before scintigraphic marker is seen in the caecum. AIM: To determine the most appropriate diagnostic criteria and clinical relevance of SIBO diagnosed using LHBT alone and combined HBT/SOCTT. SUBJECTS: 60 patients with diarrhea predominant irritable bowel syndrome (D-IBS) and 13 healthy controls. METHODS: A systematic analysis of the ability of six published diagnostic criteria to detect SIBO in D-IBS patients and controls was performed (Criteria 1: A H2 rise of ≥20ppm within 180 min; Criteria 2: A H2 rise of ≥20ppm within 90 min; Criteria 3: dual breath H2 peaks; Initial H2 rise, ≥5ppm (Criteria 4), 10ppm (Criteria 5) and 20ppm (Criteria 6) above baseline before the scintigraphic OCTT). In a subgroup of these patients the clinical relevance of these diagnostic markers was tested in an open label study of antibiotic therapy (rifaximin 1200mg/d, 10days). The short-term effect of this treatment on D-IBS symptoms in patients with and without SIBO was assessed. RESULTS: There was a close association between the time to breath H2 increase to 5ppm and 20ppm on LHBT and scintigraphic OCTT in health (R5ppm =0.896, p,0.001; R20ppm =0.860, p=0.003); however this association was lost in D-IBS patients (R5ppm =0.214, p=0.165). A 5ppmH2 increase prior to appearance of cecal contrast (criteria 4) was detected in more D-IBS patients than healthy subjects (28/60 vs. 1/13; p=0.009). This was not the case for other candidate diagnostic markers. Compared to D-IBS patients with negative findings (n=9/32), patients with a positive diagnosis of SIBO based on criteria 4 (n=27/28) had improved D-IBS symptoms following antibiotic therapy (table 1). CONCLUSIONS: Combined LHBT/scintigraphy is required for non-invasive SIBO diagnosis. The presence of a 5ppm increase in breath H2 prior to the arrival of contrast in the cecum may identify a subset of D-IBS patients with SIBO that have good clinical outcomes following antibiotic therapy.

Pro-inflammatory and anti-inflammatory cytokine response in diarrhoea-predominant Irritable bowel syndrome patients

Irritable bowel syndrome (IBS) is referred to as a functional bowel disorder which is diagnosed by a number of characteristic symptoms (Rome II criteria) in the absence of detectable structural abnormalities. Low-grade inflammation of the intestine may be one of the reasons for development of diarrhoea-predominant IBS (IBS-D). We undertook this study to estimate the serum levels of pro-inflammatory (IL-6, TNF-alpha) and anti-inflammatory (IL-10) cytokines in IBS-D patients. A total of 108 diarrhoea patients were screened. Out of these only 63 adult IBS-D patients were enrolled. Age and sex matched 62 apparently healthy controls with no GI symptoms were also recruited. Out of 63 IBS-D patients, 37 were males while there were 32 males among the controls. The patients with IBS-D were diagnosed according to the Rome II criteria. Levels of serum IL-6, TNF-alpha and IL-10 were measured in all subjects using ELISA. Mean (+/- SD) age of IBS-D patients (42.6 +/- 19.5 years) was comparable (p = 0.64) to that of controls (43.5 +/- 18.7 years). The mean (+/- SD) levels of IL-6 in IBS-D patients (32.2 +/- 12.01 pg/ml) was significantly higher (p < 0.001) than in controls (7.48 +/- 2.55 pg/ml). The levels of TNF-alpha in IBS-D patients (16.3 +/- 5.2 pg/ml) were also significantly higher (p < 0.05) than in controls (7.94 +/- 2.19 pg/ml). There was no significant difference in the serum levels of IL-10 (p = 0.23) between IBS-D patients (5.75 +/- 2.1 pg/ml) and controls (5.84 +/- 1.9 pg/ml). Our results indicate that mild inflammation is involved in IBS-D patients as proinflammatory cytokines were increased although no difference in anti-inflammatory cytokine was observed.

PWE-055 The prevalence, clinical relevance and impact on diet of lactose intolerance in a population with lactase deficiency: a randomised, double-blind, dose response study in healthy subjects and patients with diarrhoea predominant irritable bowel syndrome

IntroductionLactose Intolerance (LI) is a common clinical syndrome; however there is a lack of high quality evidence about its epidemiology, diagnosis and clinical relevance in health and patients with functional...

Diarrhoea-predominant irritable bowel syndrome: an organic disorder with structural abnormalities in the jejunal epithelial barrier

ObjectiveRecently, the authors demonstrated altered gene expression in the jejunal mucosa of diarrhoea-predominant irritable bowel syndrome patients (IBS-D); specifically, the authors showed that genes related to mast cells and the...