dysbiosis in ATB treated mice, with an increase in Lactobacilli and Clostridia populationsin the colon and eradication of Proteobacteria in the jejunum. ATB-treated mice showedless timidity and more exploratory behaviour than controls, manifested by a shorter latencyto step down (73±45 vs 214±96 s, p<0.01), increased time in the illuminated box (206±118vs 128±103 s, p<0.01) and number of zone entries (40±16 vs 28±16, p<0.01). ATB-treatedmice had mildly but statistically higher IL-4 and TNFα and lower TGFβ content in thejejunum but the inflammatory cell infiltrates were similar in both groups. The ATB-inducedmicrobiota changes and abnormal behavior normalized 2 weeks after the end of treatment.Locomotor activity, such as velocity or total distance travelled, was unchanged in ATB-treatedmice. Intraperitoneal administration of ATBs did not affect behaviour or the composition ofthe microbiota. Conclusions: Short-term ATB treatment induced a marked but transientintestinal dysbiosis, which was accompanied by altered behavior in mice. Since behaviouralchanges reversed upon normalization of the microbiota and that no change in behavior wasseen with systemic administration of the antibiotics, we conclude that behavioural changesare secondary to dysbiosis. Taken in conjunction with our recent demonstration of dysbiosis-induced visceral hyperalgesia, we speculate that dysbiosis in IBS contributes to both gastroin-testinal dysfunction and psychiatric co-morbidity. Supported by CIHR

W2032

Dietary Lectins As the Environmental “Unknown Pathogen” in Parkinson'sDisease in Caenorhabditis Elegans ModelJolene Zheng

Idiopathic Parkinson's disease (PD) is a chronic progressive motor dysfunction with a lossof dopaminergic (DAergic) neurons. The criterion of diagnosis of PD is the presence ofLewy's bodies (LB) composed of aggregated α-synuclein (α-SYN) in nigrostriatal DAergicneurons. The α-SYN and LB appear in the enteric nerve system of the gastrointestinal (GI)wall, in the brainstem, and in the higher CNS. Braak's group has proposed that an “unknownpathogen” penetrates the GI wall, transports retrogradely to the CNS, and causes PD. Dietaryphytochemical lectins can penetrate the wall of the GI tract and transfer trans-synapticallyalong nerve fibers. The lectins have been conjugated with drugs to enhance oral drugabsorption and have been exercised broadly for neuronal tracing studies. My previous studiesshowed that lectins induced α-SYN aggregation In Vitro, appeared in the CNS In Vivo andexcited a subgroup of gastric-projecting DMV neurons in ex vivo in rats. Caenorhabditiselegans (C. elegans) can be another animal model because of its short life span, variety ofgenetic amenities, low cost, and easy maintenance. The aim of this study was to utilize C.elegans model to test the novel hypothesis that dietary lectins are the “unknown pathogen”and/or facilitate the entry of “unknown pathogens” into the CNS to selectively target DAergicneurons in PD. C. elegans (B2555) expressing green fluorescence protein (GFP) in the 8DAergic neurons were cultured in agar dishes and fed E. coli (OP50) at room temperature.Co-localizations (yellow) of TRITC-lectins (red) with the GFP-DAergic neurons (green) wereobserved in 7/8 of the neurons in animals fed with E. coli and TRITC-lectins (8 μM) for 1week. Immunohistochemical staining showed that triplizations (white) of the α-SYN (Cy5,blue), the TRITC-lectins (red), and the GFP-DAergic neurons (green) were detected in C.elegans fed with the TRITC-lectins. The colocalizations or the triplizations were avoided inthe controls when the TRITC-lectins and/or the primary anti α-SYN antibody were/waseliminated. These data suggest that lectins aggregateα-SYN by transporting through intestinalsmooth muscle cells to the GFP-DAergic neurons of C. elegans. Note that lectins may alsoact as a chaperon for viruses and toxin(s) for α-SYN inclusions in PD, and the lectins-mediated insult is gradual and may be determined by the associations with other foodstructures. Supported by NIDDK #1P30 DK072476 and the LSU AgCenter. The nematodestrains used in this work were provided by the Caenorhabditis Genetics Center (NCRR).

W2033

Adjunctive Pharyngeal Electrical Stimulation in the Rehabilitation ofDysphagia Following Stroke: A Randomised Control TrialVanoo Jayasekeran, Emilia Michou, Salil Singh, Jo Borrelli, Samantha Jefferson, SatishMistry, Shaheen Hamdy

INTRODUCTION: Dysphagia in stroke is a common complication with serious con-sequences including aspiration pneumonia and increased levels of mortality. However,current treatment options for dysphagic stroke lack clinical evidence. We have previouslyshown that pharyngeal electrical stimulation (PES) can alter acute brain plasticity andswallowing in health and stroke1. Furthermore, the optimal parameters for PES in strokepatients have already been described 2. Here we now describe early results in a placebocontrolled randomised study of PES. AIMS & METHODS: Stroke patients were consecutivelyrecruited from 2 hospitals within 3 weeks from the onset of their stroke. Dysphagia wasdetermined by videofluoroscopy (VFS) using the validated Penetration-Aspiration (PA) scale.Dysphagic patients were randomly allocated to either the PES or sham stimulation. PES wasdelivered via an intraluminal pharyngeal catheter for 10 minutes at 5 Hertz for threeconsecutive days. The sham group had the catheter for the same duration without current.A follow up VFS was conducted 2 weeks later to determine changes in the PA scores anddetailed physiological timings of swallowing performance, analyzed by investigators blindedto the intervention. RESULTS: Twenty-nine patients out of 53 patients who underwentinitial VFS were dysphagic. Twenty-two of the dysphagic patients (mean age 76, age range53 -91, 15 males, 7 females) completed the protocol. There was no significant differencein age or stroke severity based on the NIHSS3 between the 2 treatment groups (p=0.48).Thirteen patients were randomized to the treatment group, and 9 to the sham group. Inthe treatment group, there was a greater reduction in the average PA scores compared tothe sham group. (p= 0.04, SD 2.92). Moreover, raw data analysis revealed a 16% reductionin cumulative PA score from baseline in the treatment group compared to a 11% increasein these scores in the sham group. With regards to physiological measures of swallow timing,the percentage change in swallow response time (SRT), which is the delay in laryngealelevation, was increased substantially by 19% in the sham group, whilst this timing wasshortened by 8% from baseline in the treatment group (p= 0.066). CONCLUSION: Pharyn-geal electrical stimulation in dysphagic stroke significantly reduces penetration-aspirationscores and appears to promote more physiological swallow timings. This study provides

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further evidence that PES may be useful in expediting the recovery of dysphagia in acutestroke. REFERENCES: 1 Fraser C., et al., Neuron 2002 ; 2 Singh S et al., Gastroenterology2005; 3. Brott TG et al., Stroke 1989

W2034

Polyunsaturated Fatty Acids Contribute to the Inflammatory Phenotype inIrritable Bowel SyndromeGerard Clarke, Peter Fitzgerald, Siobhain M. O'Mahony, Eugene Cassidy, Eamonn M.Quigley, Paul Ross, Catherine Stanton, John F. Cryan, Timothy G. Dinan

Background: Irritable bowel syndrome (IBS) is a common disorder of the gastrointestinaltract (GIT) which affects 10-15% of the population. Although the pathophysiology remainsunclear, it is increasingly being viewed as a disorder of the brain-gut axis. Accumulatingevidence points to the presence of low level immune activation in the condition. Polyunsatur-ated fatty acids (PUFAs) have recently attracted attention as being altered in a variety ofdisease states. Of these PUFAs, arachidonic acid (AA) in particular has been implicated inthe development of a proinflammatory profile in a number of immune-related disorders.AA belongs to the ω-6 family of PUFAs and is the precursor for a number of importantimmunomodulatory eicosanoids including prostaglandin E2 (PGE2) and leukotriene B4(LTB4) Aim: To investigate whether altered AA levels might contribute to the proposedproinflammatory profile in a female IBS cohort. Methods: We studied 41 female IBS patientsand 26 gender-matched controls of comparable age and BMI. Plasma AA and related PUFAswere quantified as fatty acid methyl esters (FAME) by gas chromatography analysis andflame ionization detection. Both PGE2 and LTB4 were measured in serum using commerciallyavailable ELISA assays. Results: AA levels were significantly elevated from control values inour IBS cohort (7.532 ± 0.3730 vs. 8.521 ± 0.2641 g/100g FAME, p<0.05). Downstreameffects of this elevation in AA levels included a significant increase in both PGE2 (934.2 ±145.7 vs. 1490 ± 142.3 pg/ml, p<0.05) and LTB4 (226 ± 36.7 vs. 332.2 ± 31.33 pg/ml,p<0.05). Summary: These findings suggest that elevated AA levels are a plausible source ofimmune activation in IBS. AA, PGE2 and LTB4 may represent a novel biomarker panel inthis condition.

W2035

Central Inhibitory Interaction Between Proximal and Distal Parts of the GITractJonathan Huang, Mark Kern, Syed Q. Hussaini, Safwan Jaradeh, Jyoti N. Sengupta, RezaShaker

Background: Earlier studies have shown that acid stimulation of the esophagus results inincreased cortical recruitment associated with subliminal and liminal non-painful mechanicalesophageal stimulations in healthy volunteers (Lawal et al, AJP, 2008). It is not known,however, if the cortical registration of the afferent signal from the lower GI tract is affectedby esophageal acid stimulation. Aim: To determine the effect of esophageal acid perfusionon cerebral cortical fMRI response to subliminal, luminal, and supraliminal rectal distensionin healthy volunteers. Methods: We studied 14 healthy right-handed subjects(9F, 18-40 yr)by paradigm-driven, 2-minute fMRI scanning of the left cortical hemisphere during blockdesigns of alternating intervals of randomly timed rest and 15-second intervals of rectalballoon distensions. A barostat controlled rectal distension protocol was utilized. Eachdistension protocol was done before and after 15 minutes of 0.1M PBS and 0.1N HCl perfusion(1ml/min). We quantified the number of activated voxels in the previously described regionsinvolved in registering and processing afferent signals from the rectum (prefrontal, precuneus,cingulate gyrus, insula, and sensorimotor cortex). Results: For all three distention intensities(subliminal, liminal, supraliminal), following esophageal acid perfusion, there was a signific-ant decrease in the number of activated cortical fMRI voxels associated with rectal distensionscompared to pre-acid stimulation (* subliminal p=0.002, # liminal p=0.002, + supraliminalp=0.004, figure). Esophageal perfusion with PBS did not have any effect on cortical activitydue to rectal distensions. For all test conditions, similar to earlier studies, there was a directcorrelation between the number of activated cortical voxels and distension intensity rangingfrom subliminal to supraliminal non-painful distensions. (Spearman's correlation coefficient0.66, p=0.0005). Conclusion: Esophageal acid stimulation attenuates cortical registration/processing of rectal distention-induced afferent signals suggesting the existence of a centralinhibitory interaction between the proximal and distal parts of the gastrointestinal tract.

W2036

Functional Brain Activation in Healthy Controls During SupraliminalEsophageal, Gastric and Rectal Distension: A Quantitative Meta-AnalysisBetty Jiang, Jennifer S. Labus, Eduardo Vianna, Kirsten Tillisch, Emeran A. Mayer

Background: Differences in the afferent innervation of esophagus (somatosensory, vagal,spinal), stomach (vagal,spinal) and rectum (spinal) suggest that there may be differences inbrain responses to distension of these different parts of the GI tract. Aims: Apply a quantitativemeta-analysis to map the consistent brain imaging findings during supraliminal esophageal(ED), gastric(GD)and rectal distension (RD) in healthy controls (Ctrls). Methods: Significantfoci from with-in group statistical parametric maps were extracted from brain imaging studiesexamining the central effects of supraliminal ED,GD, and RD in Ctrls. The data from eachdistension site was pooled and compared using voxel-based activation likelihood estimation(ALE) meta-analysis. Significance was determined via permutation testing and threshholdingwith a 1% false discovery rate. Results: 22 published studies (rectal=10, esophageal=6, and

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