Samefko Ludidi

Small intestinal permeability is increased in diarrhoea predominant IBS, while alterations in gastroduodenal permeability in all IBS subtypes are largely attributable to confounders

Intestinal permeability has been studied in small groups of IBS patients with contrasting findings.

Rectal hypersensitivity as hallmark for irritable bowel syndrome: defining the optimal cutoff

Background  Visceral hypersensitivity is a frequently observed hallmark of irritable bowel syndrome (IBS). Studies have reported differently about the presence of visceral hypersensitivity in IBS resulting from lack of standardization of the barostat procedure and due to different criteria used to assess hypersensitivity. We aimed to calculate the optimal cutoff to detect visceral hypersensitivity in IBS.

Revisiting concepts of visceral nociception in irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common disorder characterized by abdominal pain related to defecation with a change in bowel habit. Patients with IBS often exhibit increased visceral sensitivity, which can be tested clinically by rectal balloon distension procedures. This paper aims to give an overview of mechanisms involved in visceral hypersensitivity in IBS by reviewing recent literature.

Randomized clinical trial on the effect of a multispecies probiotic on visceroperception in hypersensitive IBS patients

Irritable bowel syndrome (IBS) is characterized by heterogeneous pathophysiology and low response to treatment. Up to 60% of IBS patients suffers from visceral hypersensitivity, which is associated with symptom severity and underlying pathophysiological mechanisms. Recently, positive effects of probiotics in IBS have been reported, but overall the response was modest. We performed a study in IBS patients, characterized by visceral hypersensitivity measured with the rectal barostat, aiming to assess the effect of 6 weeks of multispecies probiotic mix on visceral pain perception.

Does meal ingestion enhance sensitivity of visceroperception assessment in irritable bowel syndrome

Background  Visceral hypersensitivity is frequently observed in irritable bowel syndrome (IBS). Previous studies have shown that administration of a meal can aggravate symptoms or increase visceroperception in IBS patients. We investigated whether meal ingestion could increase the sensitivity of the barostat procedure for the detection of visceral hypersensitivity in IBS patients.

Alterations in serotonin metabolism in the irritable bowel syndrome

Alterations in serotonin (5‐HT) metabolism have been postulated to play a role in the pathogenesis of irritable bowel syndrome (IBS). However, previous reports regarding 5‐HT metabolism in IBS are contradicting.

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

Background Irritable 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. Aim We 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 Methods Caco-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. Results Tryptase (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). Conclusion Basolateral 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.

Su2064 Effect of a Multispecies Probiotic on Visceroperception in Hypersensitive IBS Patients

Partially Hydrolyzed Guar Gum (PHGG) Inhibits Castor Oil-Induced Diarrhea in Rats Through the Inhibition of Substance P Production Kentaro Suzuki, Yuji Naito, Kazuhiro Kamada, Syunsuke Kishimoto, Yukiko Uehara, Hideki Horie, Wataru Fukuda, Yutaka Inada, Takaya Iida, Munehiro Kugai, Toshifumi Tsuji, Hiroyuki Yoriki, Akifumi Fukui, Yasuki Higashimura, Katsura Mizushima, Kazuhiro Katada, Kazuhiko Uchiyama, Osamu Handa, Tomohisa Takagi, Nobuaki Yagi, Zenta Yasukawa, Makoto Tokunaga, Tsutomu Okubo, Lekh R. Juneja, Toshikazu Yoshikawa

Assessment of Pain Perception in Irritable Bowel Syndrome: Towards an Optimal Definition of Rectal Hypersensitivity

controlled trials (duration 4-12 weeks; PRU dose 0.5-4mg q.d.) in patients with CC were pooled, and different AE categories were compared between elderly and adults. RESULTS: 2717 patients were treated with PRU (exposure: 406 patient-yrs), of which 564 were ≥65 yrs (exposure: 63 patient-yrs). Exposure time to 2mg (recommended dose for adults) was 165 pt-yrs (n=938); exposure to 1mg (recommended dose for elderly) was 8 pt-yrs (n= 113). In the elderly, the incidence of the different AE categories was comparable between PRU and PLA, and comparable to those seen in adults except for serious AEs (SAEs). SAEs were reported at a higher rate in elderly (most commonly infections, infestations or respiratory disorders), with no difference observed between PRU and PLA (Table). Three elderly patients died, 2 on PRU, due to pneumonia or bronchitis (not considered related to study medication) and 1 on PLA due to arrhythmia/myocardial infarction. Most common AEs with PRU in both age groups were gastrointestinal symptoms (nausea, diarrhea, abdominal pain) and headache. Results in subgroups of patients 65-75 yrs and patients ≥75 yrs were similar to those observed in the whole group of elderly patients. The proportion of patients on PRU discontinuing therapy among the elderly and adults was similar. The incidence of cardiovascular AEs of interest (palpitations, corrected QT interval-related AEs, and ventricular arrhythmias) was comparable in both age groups, as well as for PRU and PLA. Cardiac ischemia and atrial arrhythmia-related AEs were more common in elderly, but their incidence was not different for PRU and PLA. The majority of ischemic and atrial rhythm-related AEs were reported by the investigator as unrelated to the study medication or doubtful. CONCLUSIONS: In 14 double-blind, PLA-controlled, Phase II/III trials of PRU, the safety and AE profiles were similar relative to PLA in adult and elderly patients with CC.

S1795 The Serotonin Precursor 5-Hydroxytryptophan Induces Rectal Allodynia in Humans

G A A b st ra ct s 1). This profile was similar to the spinal thoracic dorsal root ganglia (DRG) TRPV1-positive nociceptors innervating the esophagus (also derived from neural crest). In stark contrast, the putative placodes-derived JNG nociceptors (TRPV1+/P2X2+) lacked PPTA, GFRα3 and TrkA , but expressed TrkB. We conclude that both the neural crestand placodes-derived vagal nociceptive neurons innervate the mouse esophagus. The phenotype of neural crestderived nociceptors in the vagal and spinal (DRG) pathways is similar, but distinct from the phenotype of the vagal placodes-derived nociceptors. Supported by DK074480 and MZdSR 2007/54UK15. Table 1. Phenotypes of the TRPV1-positive neurons retrogradely labeled from the mouse esophagus