with 5-HT, BDNF and p-CREB decreased in the hippocampus but obviously increased inthe colon. We found curcumin (40 mg/kg) could reduce the immobility time of forcedswimming and the number of buried marbles (p<0.05) . 5-HT, BDNF and p-CREB weresignificantly decreased in the hippocampus but increased in the colon (BDNF p<0.001, allthe other p<0.05). Pre-treatment with 5-HT1A receptor antagonist abolished the effect ofcurcumin (40 mg/kg) in the forced swimming test(p<0.05) and marble-burying test(p<0.01),and reversed the expression of 5-HT level(p<0.05), BDNF(p<0.01). Conclusions: Our studysuggests that curcumin plays an effective role in treating IBS rats model through regulatingserotonin system, BDNF and cAMP/CREB signaling pathways via 5-HT1A receptor. Illuminat-ing the mechanism by which curcumin ameliorates IBS is crucial for selecting potentialtherapeutic multi-targeted drug for IBS. Keywords: Irritable bowel syndrome; Brain-gut axis;Depression; Serotonin; BDNF.

Su2051

Targeted Deletion of MicroRNA-29 Prevents Intestinal Hyper-Permeability &Visceral Hyperalgesia in Water Avoidance MiceSarpreet S. Basra, G. Nicholas Verne, QiQi Zhou

Background: Increasing evidence suggests that chronic stress is a major factor in the patho-physiology of several functional gastrointestinal disorders. Stress-induced visceral hypersensi-tivity has been suggested as an important pathophysiologic component underlying thecardinal symptoms of irritable bowel syndrome (IBS). We investigated whether chronicstress leads to increased intestinal permeability which may augment visceral hypersensitivityvia enhanced colonic miR-29a/b expression. The objective of the current study was todetermine if targeted deletion of miR-29a/b could prevent intestinal hyper-permeability &visceral hyperalgesia in WA stressed mice. Methods: Male miR-29a/b-/- mice and wild type(WT) mice received one hour water avoidance (WA) stress per day for 10 consecutivedays. Visceral hypersensitivity and intestinal permeability were subsequently measured. Amicroarray analysis was performed to detect specific target gene changes following targeteddeletion of miR-29a/b as well as target genes of miR-29a/b involved in visceral nociceptionand intestinal permeability. Results: WT mice with WA stress demonstrated significantlyincreased intestinal permeability & visceral hyperalgesia compared to Naive control mice.WT mice with WA stress also showed enhanced miR-29a/b expression in dorsal root ganglion(DRG) and colonic tissue which correlated with visceral hyperalgesia and intestinal hyperper-meability. However, there was no significantly increased visceral hyperalgesia or hyperper-meability in miR-29a/b-/- mice following WA stress compared with Naive controls. Conclu-sion: Deletion of miR-29a/b may prevent the development of intestinal hyperpermeabilityand visceral hyperalgesia following WA stress in mice. These data suggests that miR-29a/bmay be a new therapeutic target for attenuating visceral hypersensitivity and intestinalhyperpermeability in IBS patients.

Su2052

Effect of Rice vs. Wheat Carbohydrate Ingestion on Intestinal Gas Productionand Gastrointestinal Symptoms in Non-Constipation Irritable Bowel SyndromePatientsSittikorn Linlawan, Tanisa Patcharatrakul, Sutep Gonlachanvit

Previous studies suggested that rice is completely absorbed in the small bowel and producedless intestinal gas production and gastrointestinal (GI) symptoms compare to wheat. Thebenefit of rice carbohydrate in irritable bowel syndrome(IBS) has not been clearly demon-strated. To determine the effect of rice flour on intestinal hydrogen gas production and IBSsymptoms compared to wheat flour, 20 non-constipation IBS patients (13 F, age 46±11 yrs)underwent H2 breath test studies and GI symptom evaluations after ingestions of standardrice or wheat meals [rice or wheat noodle, 90 gm (dry weight) of rice or wheat flour] in arandomized double-blind crossover study with a 1 week-washout period. After an overnightfast, intestinal gas production and GI symptom scores in response to the standard meals(given at 8.00 am and 12.00 pm) were evaluated at baseline and every 15 minutes after thefirst standard meal for 8 hrs. The GI symptoms were evaluated using visual analog scales.Results: (data expressed as mean ± SEM) All subjects completed the studies without anyadverse events. The hydrogen(H2) and methane(CH4) concentration in breath sample wassimilar at baseline (p>0.05). Beginning at hour 5 after breakfast, the H2 and CH4 productionwas significantly increased after wheat noodle ingestion compared to rice noodle ingestion(p<0.05) The AUC of H2 and CH4 were greater after wheat noodle ingestion compared torice noodle ingestion (H2: 4120 ± 586 vs. 2267 ± 398 ppm-min, p<0.001 and CH4 : 1616± 252 vs. 946 ± 148, p<0.05). The mean symptom scores for bloating and satiety symptomswere significantly increased after wheat ingestion compared to rice ingestion (3.0 ± 0.6 vs.2.2 ± 0.6 and 3.4 ± 0.5 vs. 2.5 ± 0.5, respectively, p<0.05). Other GI symptoms includingabdominal pain, abdominal burning, nausea, urgency of stool, heartburn, belching andregurgitation were not significantly different comparing between after rice and wheat inges-tion. Conclusions: Rice flour ingestions produce significantly less intestinal gas production,bloating and satiety symptoms compared to wheat flour ingestions. This study suggests thatrice is a better source of carbohydrate for non-constipation IBS in relative to wheat carbohy-drate.

S-533 AGA Abstracts

Figure 1: Mean intestinal hydrogen(H2) level in non constipation IBS patients (N=20) (mean± SE in ppm); The H2 production was significantly increased after wheat ingestion comparedto rice ingestion.(p<0.05)

Figure 2: Mean intestinal methane(CH4) level in non constipation IBS patients (N=20) (mean± SE in ppm); The CH4 production was significantly increased after wheat ingestion comparedto rice ingestion.(p<0.05)

Su2053

Lentiviral Delivery of miR-199a Reduces Visceral Hypersensitivity ThroughTranslational Down-Regulation of TRPV1Habeeb Salameh, Buyi Zhang, QiQi Zhou, G. Nicholas Verne

Background: Many IBS patients not only have abdominal pain, but also may suffer fromvisceral hypersensitivity and heighted visceral nociception. Worse, IBS has few effectivetherapeutic agents available and mechanisms-of-disease are unclear. Objective Our goalswere to: (i) use a animal model of visceral hypersensitivity to study changes in the peripheralnervous system (dorsal root ganglion) and the GI tract (colon); (ii) identify miRNA expression,signaling and targets; (iii) verify in vitro, visceral hypersensitivity-associated changes inmiRNAs, especially miR-199a, which is complementary to the transient-receptor-potential-vanilloid-type-1 (TRPV1) gene; (iv) determine if modulating the expression of miRNAs invivo - especially miR-199a reverses associated changes and pathologic hallmarks of visceralhypersensitivity via TRPV1 signaling. Methods: (1) Male Fisher 344 rats received intracolonicinfusion (100 mg/kg) of 2,4,6-trinitrobenzene sulfonic acid (TNBS) in 50% ethanol toproduce colitis and visceral hypersensitivity. Thirty days after TNBS-colitis was healed,colonic distension was performed. (2) A lentivirus encoding the miR-199a precursor (miR-199a) and scrambled controls (scr-miR) were used for in vivo miRNA delivery. Rats receivedlentivirus containing either GFP and miR-199a expression vector (lenti-miR-199a) or GFPand control miRNA expression vector (lenti-miR-control). The lentivirus was introduced bytwo (b.i.d) IP injections; each containing 1ml lentivirus solution containing 1x109 IFU inmedia, 4ug/ml polybrene, and 1xPBS per rat. Results: Significantly decreased miR-199aexpression and increased TRPV1 expression was present in DRG and colonic tissues in ratswith visceral hypersensitivity. In vivo up-regulation of miR-199a by IP injection of lenti-miR-199a precursors decreased visceral hypersensitivity via diminished TRPV1 signaling.Conclusion: Decreased miR-199a expression in rat DRG and colon tissue leads to visceralhypersensitivity. In vivo up-regulation of miR-199a decreases visceral pain via down-modula-tion of TRPV1 signaling. Thus, miR-199 precursors are promising therapeutic candidatesto treat visceral pain.

Su2054

Combat-Training Stress Mediates Metabotypic Changes Associated WithGastrointestinal Symptoms and Altered Intestinal PermeabilityLee Cheng Phua, Clive H. Wilder-Smith, Yee Min Tan, Theebarina Gopalakrishnan,Reuben K. Wong, Xinhua Li, Enci Mary Kan, Jia Lu, Ali Keshavarzian, Eric Chun YongChan

Introduction: Physical and psychological stress have been shown to precipitate gastrointestinal(GI) symptoms and impair intestinal barrier function. The neuroendocrine and -immuneaxes, as well as probably modulation of the microbiome, are involved mechanisms, but themolecular basis of stress-induced GI manifestations remains elusive. Global urinary metabolicprofiling represents a novel approach for interrogating the multiparametric metabolic fluxesthat occur in response to pathophysiologic stimuli such as stress. Here, we characterized thestress-induced metabolic phenotype (metabotype) in soldiers during high-intensity combat-training and correlated the metabotype with changes in GI physiology, particularly the

AG

AA

bst

ract

s