IBS-D Patients Research Articles

A double-blind, placebo-controlled study to assess the effect of a probiotic mixture on symptoms and inflammatory markers in women with diarrhea-predominant IBS.

Micro-inflammation is considered an element in the pathogenesis of irritable bowel syndrome (IBS). High-sensitivity C reactive protein (hs-CRP) was previously shown to be higher in IBS compared to healthy controls, albeit within the normal range. Since probiotics may suppress micro-inflammation in the gut, we tested if they reduce symptoms and inflammatory markers (hs-CRP and fecal calprotectin (FC) in diarrhea-predominant IBS (IBS-D). The aim of this study was to assess the clinical and laboratory effects of BIO-25, a multispecies probiotic, in women with IBS-D. A double-blind, placebo-controlled study. Following a 2-week run-in, eligible women were assigned at random to a probiotic capsule or an indistinguishable placebo, twice daily for 8weeks. IBS symptoms and stool consistency were rated daily by Visual Analogue Scales (VAS) and the Bristol Stool Scale (BSS). High-sensitivity C reactive protein was tested at baseline, 4 and 8weeks. FC was tested at baseline and 8weeks. One hundred and seventy-two IBS-D patients were recruited and 107 eligible patients were allocated to the intervention (n=54) or placebo (n=53) group. All symptoms improved in both groups with no significant difference between them in symptom improvement, hs-CRP or FC levels. An 8-week treatment with BIO-25 improved symptoms in women with IBS-D, but was not superior to placebo. This rigorously designed and executed study supports the findings of other studies that did not demonstrate superiority of probiotics over placebo in IBS. High quality clinical studies are necessary to examine the efficacy of other specific probiotics in IBS-D patients since data are still conflicting.

New therapeutic options for IBS: the role of the first in class mixed µ- opioid receptor agonist and δ-opioid receptor antagonist (mudelta) eluxadoline

ABSTRACTIntroduction: Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder which represents a major cost to healthcare services. IBS-D patients represent about one-third of the IBS population and are currently treated with antispasmodics, loperamide, bile acid sequestrants and antidepressants. Alosetron and rifaximin are also available in USA, ramosetron in Japan, Korea and Thailand and ondansetron as an off-label treatment.Areas covered: This article focuses on eluxadoline, a novel pharmacological agent that has recently been approved by both the FDA and EMA for treatment of patients with IBS-D.Expert commentary: The efficacy and safety of eluxadoline in treating bowel habit alterations and pain, both in the short and long-term, make the drug a welcome addition to our therapeutic alternatives in IBS-D. Its positioning in any IBS algorithm will depend on the ‘real world’ prevalence of the small risk of sphincter of Oddi spasm and mild pancreatitis.

The effects of an artificially enhanced clinoptilolite in patients with irritable bowel syndrome

Background: Irritable Bowel Syndrome (IBS) is one of the most common gastrointestinal disorders presenting in clinical practice. IBS is a functional bowel disorder in which abdominal pain or discomfort is associated with a change in bowel habit and with features of disordered defecation.
 
 Methods: IBS candidates were enrolled in the study using the Rome III diagnostic criteria. Participants were identified as IBS-D (diarrhoea dominant), IBS-C (constipation dominant) as well as an IBS-M (mixed group). The participants were randomly assigned; for intention to treat with 750 mg potentiated clinoptilolite three times daily or placebo. The primary endpoint was to determine whether or not the patient experienced adequate relief of symptoms.
 
 Results: At the end of treatment 67% and 40% of patients were classified as overall responders in the potentiated clinoptilolite and placebo groups respectively (N=50). After week three of treatment the number of weekly responders was significantly higher (p=0.048) in the potentiated clinoptilolite group compared to the Placebo group, and at week four of treatment the number of weekly responders was borderline significant higher in the potentiated clinoptilolite group (P=0.06). Secondary endpoints were measured but the population size proved too small to realistically obtain statistical significance (p > 0.5).
 
 Conclusion: Potentiated clinoptilolite shows clinical benefit, and should be tested further in larger clinical trials. In addition, potentiated clinoptilolite also shows reduced symptoms of IBD-D and IBS-M respectively. It is recommended that clinical response to dose variation should also be further investigated in designated populations of IBS-M and IBS-D patients.

Pharmacological Approach for Managing Pain in Irritable Bowel Syndrome: A Review Article.

ContextVisceral pain is a leading symptom for patients with irritable bowel syndrome (IBS) that affects 10% - 20 % of the world population. Conventional pharmacological treatments to manage IBS-related visceral pain is unsatisfactory. Recently, medications have emerged to treat IBS patients by targeting the gastrointestinal (GI) tract and peripheral nerves to alleviate visceral pain while avoiding adverse effects on the central nervous system (CNS). Several investigational drugs for IBS also target the periphery with minimal CNS effects.Evidence of AcquisitionIn this paper, reputable internet databases from 1960 - 2016 were searched including Pubmed and ClinicalTrials.org, and 97 original articles analyzed. Search was performed based on the following keywords and combinations: irritable bowel syndrome, clinical trial, pain, visceral pain, narcotics, opioid, chloride channel, neuropathy, primary afferent, intestine, microbiota, gut barrier, inflammation, diarrhea, constipation, serotonin, visceral hypersensitivity, nociceptor, sensitization, hyperalgesia.ResultsCertain conventional pain managing drugs do not effectively improve IBS symptoms, including NSAIDs, acetaminophen, aspirin, and various narcotics. Anxiolytic and antidepressant drugs (Benzodiazepines, TCAs, SSRI and SNRI) can attenuate pain in IBS patients with relevant comorbidities. Clonidine, gabapentin and pregabalin can moderately improve IBS symptoms. Lubiprostone relieves constipation predominant IBS (IBS-C) while loperamide improves diarrhea predominant IBS (IBS-D). Alosetron, granisetron and ondansetron can generally treat pain in IBS-D patients, of which alosetron needs to be used with caution due to cardiovascular toxicity. The optimal drugs for managing pain in IBS-D and IBS-C appear to be eluxadoline and linaclotide, respectively, both of which target peripheral GI tract.ConclusionsConventional pain managing drugs are in general not suitable for treating IBS pain. Medications that target the GI tract and peripheral nerves have better therapeutic profiles by limiting adverse CNS effects.

The obestatin/ghrelin ratio and ghrelin genetics in adult celiac patients before and after a gluten-free diet, in irritable bowel syndrome patients and healthy individuals.

Ghrelin levels and obestatin/ghrelin ratio have been proposed as activity markers in ulcerative colitis, but no data are available in celiac disease (CD) and irritable bowel syndrome (IBS). Our aims were as follows: (a) to assess obestatin and ghrelin concentrations in adult active CD patients, diarrhea-predominant IBS (IBS-d), and healthy controls (HC) in relation to intestinal permeability; (b) to evaluate the ghrelin-obestatin profile in CD patients after a 1-year gluten-free diet (GFD); and (c) to establish the impact of ghrelin genetics. The study included 31 CD patients, 28 IBS-d patients, and 19 HC. Intestinal permeability, assayed by high-performance liquid chromatography determination of urinary lactulose (La)/mannitol (Ma), and circulating concentrations of obestatin, ghrelin, and their ratio were evaluated at enrollment and after GFD. The ghrelin single nucleotide polymorphisms Arg51Gln (rs34911341), Leu72Met (rs696217), and Gln90Leu (rs4684677) were analyzed. Intestinal permeability was impaired in CD patients and ameliorated after GFD. Ghrelin was significantly (P=0.048) higher and the obestatin/ghrelin ratio was significantly (P=0.034) lower in CD patients compared with both IBS-d and HC, and GFD reduced the peptide levels, but without reaching the concentrations in HC. Significant differences (P<0.05) were found in the Leu72Met polymorphism among groups, with the reduction of the GT genotype and the T allele in both CD and IBS-d patients compared with HC. Intestinal permeability is altered in CD, but not in IBS-d patients, and ghrelin levels increase in CD patients as observed in other inflammatory conditions. Moreover, a role for ghrelin genetics is hypothesized in sustaining the many pathogenetic components of these different pathologies, but with a similar symptom profile.

A Cost-Effectiveness Comparison of Alosetron, Eluxadoline, and Rifaximin in the Treatment of Irritable Bowel Syndrome with Diarrhea

1.1. Objective: The recurrent and complex Irritable Bowel Syndrome (IBS) has major impact on healthcare cost and quality-of-life (QoL) with highest prevalence and lowest QoL score of diarrhea predominant IBS (IBS-D). However, to treat IBS-D, Alosetron, Eluxadoline and Rifaximin are the only FDA-approved medications. There is a lack of standardized guidelines to recommend optimal therapy. Therefore, the aim of the study was to develop a decision-making analytical model to evaluate the economic and humanistic implications of the three approved medications in individuals with IBS-D. 1.2. Method: This study included estimates from clinical trials which measured IBS quality of life (IBS-QoL) for each treatment compared to placebo. The costs for individual treatment arm were the average wholesale prices from Red Book. A 12-week cost-effective decision-making analytical model was developed. The costs for the associated adverse events were weighted by the respective probabilities to evaluate the cost per quality-adjusted life year (QALY) gain and incremental cost-effectiveness ratio (ICER) as the study outcomes. 1.3. Results: The management cost for unit increment of QALY with respect to placebo was the least for Rifaximin treatment ($21,457); and the highest for alosetron treatment ($138,111). The ICER values of base case indicated dominance of Rifaximin over Eluxadoline by $291,123; and of Eluxadoline over alosetron by $482,767. In a willingness-to-pay range of $50,000 to $100,000, Rifaximin is the preferred option for 80% of IBS-D patients. 1.4. Conclusion: The results indicate that Rifaximin was the most cost-effective treatment among all the three regimens to manage IBS-D symptoms based on the parameters considered in this study.

The Majority of Quality of Life Domains Are Impacted in IBS Patients: A Need for Intervention

Introduction: Irritable bowel syndrome (IBS) is a widespread gastrointestinal disorder affecting up to 20% of the U.S. population. While it is known that quality of life (QOL) is greatly affected in IBS patients, there is not much evidence regarding what areas of quality of life are involved. This study determined what domains of QOL are most impacted in a cohort of IBS patients at a tertiary care center and if age or BMI have an influence on their QOL. Methods: Patients diagnosed with IBS by Rome III criteria visiting a general gastroenterology clinic at a tertiary medical center were surveyed using the IBS-QOL. IBS-QOL is a psychometrically validated questionnaire which assesses overall quality of life and along eight subscales: dysphoria, interference with activity, body image, health worry, food avoidance, social reaction, sexual, and relationships. IBS-QOL and its subscales are both scored from 0-100. Lower scores suggest worse quality of life. Demographic data including age, gender, race; clinical data including BMI and IBS subtype (IBS-U, IBS-C, IBS-D); responses to IBS-QOL questionnaires were collected and analyzed. We compared overall IBS-QOL and its subscales by subtype as well as by age and BMI. Analysis of variance (ANOVA) or non-parametric Kruskal-Wallis tests assessed differences in continuous variables. Pearson's chi-square tests were used for categorical factors. Post-hoc comparisons were done at a significance of 0.017 (0.05/3 comparisons). Spearman's correlation coefficients assessed if IBS QOL correlated to age or BMI. Results: A total of 80 patients were analyzed [mean age 49yrs, 85% female]. Overall IBS-QOL and all subscales except body image and health worry were found to be significantly associated with diagnosis (Table 1). IBS-D patients had significantly lower QOL than IBS-C; there was no significant difference between either of these two groups and the IBS-U group (Figures 1&2). There was no correlation between age or BMI and any IBS-QOL subscale (Table 2).Figure 1Figure 2Conclusion: Majority of QOL domains are impacted in IBS patients. Providers should acknowledge dysphoria, interference with activity, food avoidance, social reactions and relationship issues in these patients. Further study is needed to determine possible treatment modalities to improve QOL and these domains in IBS patients. A multidisciplinary clinic with nutrition, psychology and psychiatry resources may be beneficial in management of IBS patients. IBS-D patients may require more intensive therapies.Figure 3

Efficacy and Safety of Eluxadoline in IBS-D Patients Who Report Prior Inadequate Symptom Control with Loperamide

Efficacy and Safety of Eluxadoline in IBS-D Patients Who Report Prior Inadequate Symptom Control with Loperamide

P2Y1, P2Y2, and TRPV1 Receptors Are Increased in Diarrhea-Predominant Irritable Bowel Syndrome and P2Y2 Correlates with Abdominal Pain.

Previous studies indicated that P2Y1 and P2Y2 receptors, which are widely distributed in the enteric nervous system, are related to pain, while TRPV1 may contribute to visceral pain and hypersensitivity states in irritable bowel syndrome (IBS). Other studies showed that ATP activates the capsaicin-sensitive TRPV1 channel via P2Y receptors. To detect the expression of P2Y1, P2Y2, and TRPV1 receptors in diarrhea-predominant IBS (IBS-D) patients and analyze any correlations with abdominal pain and to investigate interactions between P2Y receptors and the TRPV1 receptor in IBS-D patients. Rectosigmoid biopsies were collected from patients with IBS-D (n=36) and healthy controls (n=15). Abdominal pain was scored using a 10-cm visual analogue scale. Expression levels of P2Y1, P2Y2, and TRPV1 receptors in rectosigmoid biopsies were determined by real-time PCR and double-labeling immunofluorescence with specific antibodies. Both mRNA and protein expression levels of P2Y1, P2Y2, and TRPV1 receptors were increased in IBS-D compared with controls. Of these receptors, P2Y2 expression correlated with the maximum pain scores (p=0.02, r=0.63, Spearman correlation) in IBS-D patients. However, no relationships were detected between P2Y receptors and the TRPV1 receptor. In the present study, we identified an increased expression of P2Y1 and P2Y2 receptors in the rectosigmoid mucosa of IBS-D patients, and P2Y2 correlated with abdominal pain. Furthermore, we identified an increase in TRPV1 expression; however, there were no correlations found between P2Y receptors and the TRPV1 receptor.

Interplay between bile acid metabolism and microbiota in irritable bowel syndrome

Irritable bowel syndrome (IBS) physiopathology is multifactorial and roles for both microbiota and bile acid (BA) modifications have been proposed. We investigated role of dysbiosis, transit pattern and BA metabolism in IBS. Clinical data, serum, and stool samples were collected in 15 healthy subjects (HS), 16 diarrhea-predominant (IBS-D) and 15 constipation-predominant IBS (IBS-C). Fecal microbiota composition was analyzed by real-time PCR. Sera and fecal BA profiles, 7α-C4 levels, and in vitro BA transformation activity by fecal microbiota were measured by mass spectrometry. Serum Fibroblast Growth Factor 19 (FGF19) was assayed by ELISA. Dysbiosis was present in IBS patients with an increase in Escherichia coli in IBS-D patients (p = 0.03), and an increase in Bacteroides (p = 0.01) and Bifidobacterium (p = 0.04) in IBS-C patients. Sera primary and amino-conjugated BA were increased in IBS-D (63.5 ± 5.5%, p = 0.01 and 78.9 ± 6.3%, p = 0.03) and IBS-C patients (55.9 ± 5.5%, p = 0.04 and 65.3 ± 6.5%, p = 0.005) compared to HS (37.0 ± 5.8% and 56.7 ± 8.1%). Serum 7α-C4 and FGF19 levels were not different among all three groups. Fecal primary BA were increased in IBS-D patients compared to HS, including chenodeoxycholic acid which has laxative properties (25.6 ± 8.5% vs 3.5 ± 0.6%, p = 0.005). Bile acid deconjugation activity was decreased in IBS-D (p = 0.0001) and IBS-C (p = 0.003) feces. Abdominal pain was positively correlated with serum (R = 0.635, p < 0.001) and fecal (R = 0.391, p = 0.024) primary BA. Different sera and fecal BA profiles in IBS patients could be secondary to dysbiosis and further differences between IBS-C and IBS-D could explain stool patterns. This study opens new fields in IBS physiopathology and suggests that modification of BA profiles could have therapeutic potential.

High-sensitive C-Reactive Protein as a Marker for Inflammation in Irritable Bowel Syndrome.

Recent studies demonstrated low-grade inflammation in patients with irritable bowel syndrome (IBS). However, these studies have been relatively small and do not enable examination of this factor in different subtypes of IBS and the possibility of confounding effects of comorbidities that may be associated with inflammatory responses. To investigate the association between high-sensitive C-reactive protein (hs-CRP) and the diagnosis of IBS, IBS subtypes, symptoms' severity, and IBS-associated comorbidities. This cross-sectional study uses data from a large matched case-control study of IBS subjects and healthy controls (HC). hs-CRP levels were measured in all subjects. IBS diagnosis was determined by Rome III criteria, negative screening blood tests, and normal colonoscopy. Subjects were evaluated for IBS severity and associated pain and psychological comorbidities. A total of 242 IBS patients and 244 HC were studied. Median hs-CRP levels in the IBS group were significantly higher than in HC (1.80; interquartile range, 0.7 to 4.04 mg/L vs. 1.20, interquartile range, 0.5 to 2.97 mg/L respectively, P<0.006). Levels were highest in IBS-D patients with greater disease severity. Hs-CRP levels mildly correlated with symptoms severity (r=0.169, P=0.009); this correlation was stronger for the IBS-D patients (r=0.27, P=0.006). IBS was a significant independent predictor (P=0.025) for higher hs-CRP levels, whereas other pain and psychological comorbidities were not. Given these observations of cross-sectional differences in hs-CRP between IBS subtypes and severity, independent of pain and comorbidities, more research is needed to explore a possible role of low-grade inflammation in the pathogenesis and/or clinical presentation of IBS.

Altered Colonic Bacterial Fermentation as a Potential Pathophysiological Factor in Irritable Bowel Syndrome.

Dysbiosis leading to abnormal intestinal fermentation has been suggested as a possible etiological mechanism in irritable bowel syndrome (IBS). We aimed to investigate the location and magnitude of altered intestinal bacterial fermentation in IBS and its clinical subtypes. IBS patients who satisfied the Rome III criteria (114) and 33 healthy controls (HC) were investigated. Intestinal fermentation was assessed using two surrogate measures: intestinal intraluminal pH and fecal short-chain fatty acids (SCFAs). Intraluminal pH and intestinal transit times were measured in the small and large bowel using a wireless motility capsule (SmartPill) in 47 IBS and 10 HC. Fecal SCFAs including acetate, propionate, butyrate, and lactate were analyzed by capillary gas chromatography in all enrolled subjects. Correlations between intestinal pH, fecal SCFAs, intestinal transit time, and IBS symptom scores were analyzed. Colonic intraluminal pH levels were significantly lower in IBS patients compared with HC (total colonic pH, 6.8 for IBS vs. 7.3 for HC, P=0.042). There were no differences in total and segmental pH levels in the small bowel between IBS patients and HC (6.8 vs. 6.8, P=not significant). The intraluminal colonic pH differences were consistent in all IBS subtypes. Total SCFA level was significantly lower in C-IBS patients than in D-IBS and M-IBS patients and HC. The total SCFA level in all IBS subjects was similar with that of HC. Colonic pH levels correlated positively with colon transit time (CTT) and IBS symptoms severity. Total fecal SCFAs levels correlated negatively with CTT and positively with stool frequency. Colonic intraluminal pH is decreased, suggesting higher colonic fermentation, in IBS patients compared with HC. Fecal SCFAs are not a sensitive marker to estimate intraluminal bacterial fermentation.

Psychological and physiological aspects of stress in atopic patients

mucosal humoral immunity has been identified in the small intestine, however little is known about the type of antibody response. We characterized the mucosal immunoglobulins (Ig) isotype and its association with IBS pathophysiology. Methods: Mucosal jejunal biopsies, stool and blood samples wereobtained fromhealthyvolunteers (H;n=18)andage-matched participantsmeeting diarrhoea-IBS Rome III criteria (IBS-D; n=20). Bowel movements, stool consistency and abdominal pain were monitored (10 days prior to biopsy). Psychological stress and depressionwere assessedwith validated questionnaires. The number and ultrastructure of mucosal plasma cells were determined by transmission electron microscopy, and mucosal IgG+ cells were quantifiedby immunofluorescence. Igswere quantified in stool and blood by ELISA technique. Results: The number of mucosal IgG+ cells and plasma cells was increased in IBS-D patients, the later in close proximity to nerve fibres, respect to H (P<0.05). Plasma cells displayed signs of activation but the presence of cell clusters was more abundant in the IBS-D group. IgG in faeces was higher in IBS-D than in H (P<0.05). Plasma cells-nerves proximity correlated with stress and depression, and IgG in faeces correlated with abdominal pain (P<0.05). Conclusion: IgG production rises as a distinctive marker of mucosal immuneactivity in associationwith clinical characteristics in IBS-D. Studies aimed at determining IgG subtype and antigens eliciting such responses warrant further investigation.

Reduction of butyrate- and methane-producing microorganisms in patients with Irritable Bowel Syndrome.

The pathophysiology of irritable bowel syndrome (IBS) remains unclear. Here we investigated the microbiome of a large cohort of patients to identify specific signatures for IBS subtypes. We examined the microbiome of 113 patients with IBS and 66 healthy controls. A subset of these participants provided two samples one month apart. We analyzed a total of 273 fecal samples, generating more than 20 million 16S rRNA sequences. In patients with IBS, a significantly lower microbial diversity was associated with a lower relative abundance of butyrate-producing bacteria (P = 0.002; q < 0.06), in particular in patients with IBS-D and IBS-M. IBS patients who did not receive any treatment harboured a lower abundance of Methanobacteria compared to healthy controls (P = 0.005; q = 0.05). Furthermore, significant correlations were observed between several bacterial taxa and sensation of flatulence and abdominal pain (P < 0.05). Altogether, our findings showed that IBS-M and IBS-D patients are characterized by a reduction of butyrate producing bacteria, known to improve intestinal barrier function, and a reduction of methane producing microorganisms a major mechanism of hydrogen disposal in the human colon, which could explain excess of abdominal gas in IBS.

Comparative effect of electroacupuncture and moxibustion on the expression of substance P and vasoactive intestinal peptide in patients with irritable bowel syndrome

ObjectiveTo compare the impacts of electroacupuncture (EA) and moxibustion (Mox) on the primary gastrointestinal symptoms and the expressions of colonic mucosa-associated neuropeptide substance P (SP) and vasoactive intestinal peptide (VIP) in patients with either diarrhea-predominant or constipation-predominant irritable bowel syndrome (IBS-D and IBS-C, respectively). MethodsEighty-five IBS patients were randomly allocated to the EA and Mox groups. Zusanli (ST 36) and Shangjuxu (ST 37) were selected as acupoints for electroacupuncture or warm moxibustion treatment once a day for 14 consecutive days. Before and after the treatment sessions, a Visual Analog Pain Scale and the Bristol Stool Form Scale were used to evaluate gastrointestinal symptoms. There were four dropout cases, leaving 81 participants (41 with IBS-D and 40 with IBS-C) who volunteered to undergo colonoscopy before and after the treatment sessions. During colonoscopy, sigmoid mucosa were collected to detect SP and VIP expression using immunohistochemistry assay. ResultsBoth EA and Mox treatments were effective at relieving abdominal pain in IBS-D and IBS-C patients. However, Mox was more effective at reducing diarrhea in IBS-D patients, whereas EA was more effective at improving constipation in IBS-C patients. EA and Mox treatments both down-regulated the abnormally increased SP and VIP expression in the colonic mucosa, with no significant difference shown between the two treatments. ConclusionBoth EA and Mox treatments are effective at ameliorating gastrointestinal symptoms by reducing SP and VIP expression in the colonic mucosa of IBS patients.

The intestinal barrier in irritable bowel syndrome: subtype-specific effects of the systemic compartment in an in vitro model.

BackgroundIrritable bowel syndrome (IBS) is a disorder with multifactorial pathophysiology. Intestinal barrier may be altered, especially in diarrhea-predominant IBS (IBS-D). Several mediators may contribute to increased intestinal permeability in IBS.AimWe aimed to assess effects of tryptase and LPS on in vitro permeability using a 3-dimensional cell model after basolateral cell exposure. Furthermore, we assessed the extent to which these mediators in IBS plasma play a role in intestinal barrier function.Materials and MethodsCaco-2 cells were grown in extracellular matrix to develop into polarized spheroids and were exposed to tryptase (10 - 50 mU), LPS (1 - 50 ng/mL) and two-fold diluted plasma samples of 7 patients with IBS-D, 7 with constipation-predominant IBS (IBS-C) and 7 healthy controls (HC). Barrier function was assessed by the flux of FITC-dextran (FD4) using live cell imaging. Furthermore, plasma tryptase and LPS were determined.ResultsTryptase (20 and 50 mU) and LPS (6.25 – 50 ng/mL) significantly increased Caco-2 permeability versus control (all P< 0.05). Plasma of IBS-D only showed significantly elevated median tryptase concentrations (7.1 [3.9 – 11.0] vs. 4.2 [2.2 – 7.0] vs. 4.2 [2.5 – 5.9] μg/mL; P<0.05) and LPS concentrations (3.65 [3.00 – 6.10] vs. 3.10 [2.60-3.80] vs. 2.65 [2.40 – 3.40] EU/ml; P< 0.05) vs. IBS-C and HC. Also, plasma of IBS-D increased Caco-2 permeability versus HC (0.14450 ± 0.00472 vs. 0.00021 ± 0.00003; P < 0.001), which was attenuated by selective inhibition of tryptase and LPS (P< 0.05).ConclusionBasolateral exposure of spheroids to plasma of IBS-D patients resulted in a significantly increased FD4 permeation, which was partially abolished by selective inhibition of tryptase and LPS. These findings point to a role of systemic tryptase and LPS in the epithelial barrier alterations observed in patients with IBS-D.

Reply

We thank Drs Sood and Ford for their careful assessment of our recent article, and agree with most of their comments and the recommendation that further validation is warranted in a larger sample, including patients not evaluated at a tertiary care center. We also agree with their careful appraisal of the current state of biomarker discovery and validation in irritable bowel syndrome (IBS). We would, however, wish to clarify a few points. First, although the study was conducted at Mayo Clinic, patients were drawn from the communities living within 120 miles from Rochester, Minnesota, and therefore they do not represent tertiary referral population seen at Mayo Clinic, and are representative of IBS patients who sought assistance from a gastroenterologist. Second, the evidence in the literature, including the cited study from the Leeds group (Neurogastroenterol Motil 2012;24:983–e538) suggests that 25%-50% of patients with IBS-D have evidence of bile acid malabsorption, and studies of colonic transit using scintigraphy or radiopaque markers show that approximately 33% of patients with IBS have abnormal transit (Clin Gastroenterol Hepatol 2008;6:772–781; Am J Gastroenterol 2012;107:754–760). Therefore, these 2 biomarkers have relatively high prevalence and are eminently actionable (hence our focus on validating biomarkers of treatable mechanisms in IBS [Neurogastroenterol Motil 2014;26:1677–1685]), in contrast with many other proposed biomarkers discussed in the comment. Third, contrasting IBS from organic diseases (such as inflammatory bowel disease or celiac disease) is not difficult given the presence of rectal bleeding or physical findings on examination in IBD and the ease of screening for celiac disease with serologic testing. Therefore, our data support the notion that the 2 biomarkers (colonic transit and test for bile acid diarrhea) provide physicians with the opportunity to provide their patients with specific therapies based on pathophysiological mechanism. We have recently proven this concept in IBS-D patients with elevated fecal bile acid excretion treated with the bile acid sequestrant, colesevelam (Aliment Pharmacol Ther 2015;41:438–448), and in many studies that targeted colonic transit with alosetron, tegaserod, prucalopride, linaclotide, lubiprostone, and so on (Clin Pharmacol Ther 2010;87:748–753). Combining Biomarkers in Irritable Bowel Syndrome: A Forward Step Toward Making a Positive Diagnosis and Directing Therapy?GastroenterologyVol. 148Issue 7PreviewCamilleri M, Shin A, Busciglio I, et al. Validating biomarkers of treatable mechanisms in irritable bowel syndrome. Neurogastroenterol Motil 2014;26:1677–1685. Full-Text PDF

Su1375 Healthcare Cost of Irritable Bowel Syndrome Based on Self-Reported Questionnaires in an Asian Cohort

G A A b st ra ct s significant for individual polyols: mannitol (p=0.002), sorbitol (p<0.001), and xylitol (p= 0.014). There was no significant difference in intake of fructose, constituent lipids, total fiber, or total grains between the 2 groups. However, IBS patients consumed significantly more whole grain flour (p=0.028) and whole grain bread (p=0.001) than controls, but similar amounts of refined flour and refined flour bread. Conclusions: IBS-D patients consumed less FODMAPs including lactose and polyols than healthy controls. Whether this is due to IBS patients consciously or unconsciously avoiding foods that trigger their symptoms remains unclear. On the other hand, IBS patients consumed more whole grains. These data suggest that many IBS-D patients alter their dietary FODMAP and grain intake and may prove useful when counseling IBS patients on dietary interventions.

Su1371 Non-Traumatic Stressful Events At the Time of Abdominal Pain Onset Is a Marker of Current Psychological but Not GI Health in More Severe IBS Patients

BACKGROUND. IBS is a chronic, potentially disabling GI disorder that affects up to 50 million Americans. Despite its prevalence, IBS symptoms of a significant proportion of individuals go unrecognized or untreated. Efforts to improve case detection by encouraging MDs to adopt Rome diagnostic criteria have been suboptimal. An alternative approach is to improve symptom reporting through the use of self-administered checklists or screeners that increase individuals' awareness and knowledge of the diagnostic symptoms of IBS. When shared with the treating gastroenterologist (GE), information derived from symptom checklists have potential to improve diagnostic accuracy, conserve time and resources, strengthen patient engagement, and help patients obtain improved quality of life and relief for the disorder for which they seek care. These goals have been hampered by the lack of a brief, easy to administer, simple to score/interpret, and validated measure.AIM. To examine the diagnostic accuracy of a brief (4 True-False questions) screening tool of IBS symptoms based on Rome III criteria. METHOD. 384 IBS patients (80% F; M age = 41 yrs.) completed the IBS screener (4-IBS) that was embedded in a test battery administered at pretreatment assessment of an NIH trial for IBS. Assessment included the IBS Symptom Severity Scale, IBS QOL, Brief Symptom Inventory (distress), SF-12, Visceral Sensitivity Inventory (VSI, fear of visceral sensation). Administration time was < 1 minute. GI symptoms were assessed by a board certified GE who confirmed Rome diagnosis (‘gold standard') in all cases. GEs were blind to patient responses to the 4-IBS when Rome diagnosis was made. RESULTS. Agreement between GE diagnosis and 4-IBS screener diagnosis was good to excellent. The 4-IBS symptom screener correctly diagnosed IBS in 71% of IBS-C patients and 75% of IBSD patients. Agreement was strongest (90%) for IBS-M patients. Patients for whom there was greatest agreement between self-report and GE diagnosis were characterized by stronger fears of GI symptoms (VSI, p<.05).CONCLUSION. Data corroborated the diagnostic validity of a brief, self-report IBS screener for identifying patients likely to meet Rome criteria for IBS. While a clinical evaluation is necessary to confirm IBS and rule out other potential conditions whose GI symptoms mimic those of IBS, the 4-IBS screener may prove useful for identifying IBS patients in busy clinical settings. A self-screener may be particularly useful for early identification of patients who drive health care use. For patients with stronger fears of GI symptoms (high VSI), their hypervigilance to core IBS symptoms and features (e.g., pain onset associated with change in stool consistency) may promote accurate diagnosis of IBS relative to less fearful patients with lower attentional focus to visceral sensations. Acknowledgements: NIH grant DK77738

Mo1279 Durability of Benefit in IBS-D Patients Responding to a 2-Week Course of Rifaximin: Results From TARGET 3

Mo1279 Durability of Benefit in IBS-D Patients Responding to a 2-Week Course of Rifaximin: Results From TARGET 3