AGA Abstracts double-blind, and placebo-controlled study was performed in 49 IBS patients (probiotics: 25, placebo: 24) diagnosed according to the Rome III criteria. Subjects were randomized to receive probiotics (Mixture of Bifidobacterium longum, Bifidobacterium breve, Bifidobac- terium lactis, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Streptococcus thermo- philus - twice a day) or placebo for 4 weeks. A gastrointestinal symptom questionnaire was used for evaluating abdominal pain, diarrhea, constipation, bloating, gas, stool frequency, and daily life activities with a visual analogue scale and bacterial DNAs in feces were analyzed by quantitative real-time PCR assays before and after each treatment. Results: Both groups showed similar symptomatic improvement in terms of diarrhea and constipation, but the severity and frequency of abdominal pain and defecation were much more improved in the probiotics group (p<0.05). At week 4, the probiotics group reported more improvement in abdominal pain, satisfaction with bowel habit, and daily life activities than the placebo group (p<0.05). Thirty three (probiotics: 18, placebo: 15) of all the subjects were analyzed by real-time PCR for fecal microbiota. Baseline fecal microbiota were not different between the placebo and probiotics groups. After 4 weeks of probiotics treatment, total bacterial numbers of Bifidobacterium lactis (mean; from 6.1 to 7.5 log10 cells/g in feces, p=0.001), Lactobacillus rhamnosus (mean; from 2.8 to 4.8 log10 cells/g in feces, p=0.001), and Streptococcus thermophilus (mean; from 4.8 to 5.4 log10 cells/g in feces, p=0.03), were increased only in the probiotics group (p<0.05). But, total bacterial number of B. longum, B. bifidum, L. Acidophilus, C. perfringens, E. coli, Bacteriodes did not change in both groups after 4 weeks of treatment. According to the subgroup analysis, the group with 10-fold increase in total bacterial number of B. lactis showed higher improvement rate in the frequency of abdominal pain than the group with no change of the bacterial number (91.9% vs 45.5%, p=0.03). Conclusions: Alteration of gut microbiota after probiotics treatment correlates with sympto- matic improvement in IBS patients in terms of abdominal pain and stool frequency. These results support that intestinal microbiota may have a function of modulating intestinal perception in IBS. Tu1421 In Vitro Characterization of the Human Colon: A Pioneering Effort Tiong Cheng Sia, David Wattchow, Simon J. Brookes, Nicholas J. Spencer, John W. Arkwright, Philip G. Dinning Purpose: Colonic motility disorders cause significant societal and financial burdens, and little is know of the abnormalities that underpin it. We have recently published data in which we successfully recorded motor patterns from entire segments of human colon excised for colonic disease or dysfunction. Here we present a proof-of-principle study in which contractile events in excised human colon are recorded with fibre-optic manometry catheter. Methods: Entire segments of human colon (descending colon to rectum) were removed from patients with known colonic malignancy and placed in temperature controlled organ baths filled with Krebs. The fibre-optic catheter, was attached to a metal rod positioned above the tissue bath. Lanyards were placed over sensors on the catheter at 2cm intervals. The lanyards were then clipped to the serosa and adjusted to provide suitable tension. Motility was captured for 1 hour before the specimens were sent to pathology. Results: A total of 8 (n:8) specimens were studied. In 7 propagating activity was detected and in 6 the activity was present within the first 15 minutes. In 6 of 7 the frequency of propagating events remained constant (0.44 ¬¬± 0.11/min) throughout the recording period. In 1 specimen the frequency of propagating events increase with time from 0.33/min to 0.73/min. In 6 specimens a demonstrable increase in baseline tone occured over 1 hr recording period. Conclusion: These preliminary data demonstrate the feasibility of using the fibreoptic cathether to record In Vitro human colonic motility patterns. These data have the potential to provide valuable insight into the intrinsic mechanisms controlling colonic motility. Tu1422 PH Profile Varies Along the Small Intestine in Healthy Subjects and Patients With Irritable Bowel Syndrome? David B. Lalezari Background: Intestinal transit is altered in patients with Irritable Bowel Syndrome (IBS). Gastric and intestinal transit time can be assessed by a new method, a wireless pH capsule, based on changes in pH milieu in various segments of the gut. We postulated that altered transit may be associated with a change in small bowel pH profile in patients with IBS which may also contribute to symptoms associated with IBS. Aim: To measure gastrointestinal pH profile and small intestine transit time (SITT) in healthy controls and patients with D- IBS and IBS with alternating bowel habits. Methods: Nine IBS patients (3 males, mean age 35 yrs) and 10 healthy subjects (6 males, mean age 33 yrs) were studied at Cedar-Sinai Medical Center, Los Angeles. Patients were selected based on Rome 3 criteria. Intestinal pH profile and SITT were assessed by a wireless motility pH and pressure capsule (Smart Pill). Location of the capsule was identified by changes in pH that correspond to gastric, small bowel and cecal profiles. Half an hour after the capsule was emptied from the stomach subjects received 10 grams of lactulose, and recording continued until the capsule entered the large bowel (documented by a drop in pH). SITT was compared between the groups. Mean pH values were measured for each of the 4 quartiles of capsule residence in small intestine and compared both within and between groups. Data presented as mean or median, ANOVA, p<0.05 for significance. Results: The proximal small bowel was significantly more acidic, compared to distal segments, in both healthy subjects and IBS patients, with no difference between the two groups. Conclusion: This study, the first to investigate pH changes along the small bowel in patients with IBS, shows the presence of a gradient of pH along the small bowel, in both IBS and healthy subjects, the distal being less acidic. These finding may be of importance in better understanding the physiology of IBS and small bowel homeostasis. Comparison of Demographics characteristics between Control and IBS study groups S-828 AGA Abstracts IBS vs Control Gastrointestinal mean pH profile for small intestine. The mean pH is repres- ented for each quartile of the SI (Q1, Q2, Q3, Q4). There was no significant difference between the groups. Tu1423 Effects of Linaclotide on Straining Associated With Bowel Movements in Patients With Irritable Bowel Syndrome With Constipation (IBS-C): A Post Hoc Analysis of Pooled Data From Two Phase 3 Trials Anthony Lembo, Satish S. Rao, Steven J. Shiff, Bernard J. Lavins, James E. MacDougall, Kelvin Shi, Harvey Schneier, Mark G. Currie, Jeffrey M. Johnston Introduction: Patients with IBS-C experience abdominal pain and altered bowel habits. The extent of straining associated with bowel movements (BMs) in these patients is less well defined. Linaclotide, a 14-amino-acid, minimally-absorbed peptide, improved abdominal and bowel symptoms (including straining) in two double-blind, placebo-controlled Phase 3 trials in patients with IBS-C. Aims: To examine the distribution of severity of straining associated with spontaneous BMs (SBMs), the responder rates for a clinically meaningful change in straining, and the correlation of bowel habits and abdominal symptoms with the constipation severity score. Methods: Pooled data from the 12-week Treatment Period of two Phase 3 IBS-C trials were used in these post hoc analyses. For each SBM, straining was scored on a 5-point scale (1: Not at all, to 5: An extreme amount). A 7-point balanced scale was used for the patient rating of improvement in straining during BMs over the past 7 days (1: Completely improved, to 7: As bad as I can imagine). For patients reporting “Somewhat improved” on the 7-point balanced scale for improvement in straining, the mean change from baseline straining was calculated and used as the threshold for the responder definition for clinically meaningful change in straining. The correlation (Pearson) between constipation severity and bowel and abdominal habits (straining, CSBMs, SBMs, stool consist- ency, abdominal pain, bloating, and cramping) was calculated. Constipation severity was rated weekly on a 1 (none) to 5 (very severe) scale. Results: The pooled intent-to-treat population included a total of 797 placebo- and 805 linaclotide-treated patients. At baseline, 54% of IBS-C patients reported a great deal/an extreme amount of straining, and 31% reported a moderate amount (Table 1). Linaclotide vs placebo treatment significantly improved straining (LS mean change from baseline: linaclotide -1.3 vs placebo -0.6, p<0.0001). A threshold change of 1.1 from baseline straining was determined to be a clinically meaningful change; significantly more linaclotide-treated patients (57.5%) vs placebo-treated patients (27.1%) experienced clinically meaningful change in straining (Table 2). Linaclotide treatment resulted in a 40% decrease in SBMs associated with “a great deal” or “extreme amount” of straining, vs a 27% decrease for placebo (Pretreatment Period minus Treatment Period). Of the bowel and abdominal symptoms assessed, straining was most highly correlated with the overall constipation severity score (r=0.71, p<0.0001, data not shown for the other symptoms). Conclusions: IBS-C patients experience significant straining with BMs and linaclotide treatment resulted in clinically meaningful improvements in straining associated with SBMs in these patients. Table 1. Distribution of Straining for SBMs Note: Pooled Phase 3 IBS-C ITT Population, 12-Week Treatment Period. Patients who did not have an SBM during the time period analyzed were excluded. Table 2. Straining Responder Results Using the Symptom-Specific Thresholds for Clinical Meaningfulness