2.941, 95% CI [1.446-5.980]). For IBS-M patients, the presence of FS has a sensitivity of 50%, a specificity of 91%, a positive predictive value of 24% and a negative predictive value of 91%. Conclusion: In FBD patients, FS are associated to IBS-M and not to diarrhea (IBS with diarrhea or functional diarrhea). Su2089 Validation of the Use of the ICD-10 Diagnostic Code for Irritable Bowel Syndrome in the Swedish National Patient Register Navkiran Jossan, Ann-Sofie Backman, Marie Linder, Maria Altman, Magnus Simren, Ola Olen, Hans Törnblom Background: Irritable bowel syndrome (IBS) is a diagnosis based on symptom criteria. In order to perform epidemiologic studies based on national health-care registers there is a need to assess the accuracy of the diagnostic code in clinical practice at different time points. Aim: To evaluate the positive predictive value of the ICD-10 (International Classification of Diseases, version 10) code for IBS in Sweden in hospital based outpatient care during 2005 (using the Rome II criteria) and 2010 (Rome III criteria). Methods: We identified all Swedish adults that had received the ICD-10 code for IBS as the main diagnosis during hospital- based outpatient care in 2005 and 2010 by use of the Swedish National Patient Register. We excluded individuals from the IBS cohort if they had been diagnosed with predefined diagnoses, incompatible with IBS, during a time span of 6 months before or after the IBS diagnosis. The National Board of Health and Welfare generated a random sample of 300 identities. Each medical record was retrieved and read by two of the authors (N.J. and H.T.) who noted if symptoms compatible with IBS according to Rome II criteria (2005 cohort) or Rome III criteria (2010 cohort) could be identified. Results: We received a total of 248 medical records (2005, n=127; 2010, n=121). In 173 patients (70%), the diagnosis fulfilled diagnostic criteria with a high certainty and in 75 patients (30%) it did not. The proportions of valid diagnoses were similar in 2005 (Rome II criteria, 68%) and 2010 (Rome III criteria, 72%) (p=.41). Out of the 75 cases that did not fulfill diagnostic criteria, 24 were labeled "probable IBS" because of insufficient medical data. There was no difference when comparing tertiary (72% correct) and secondary care (69% correct) (p=.62), but a significant difference in accuracy was noted comparing departments of internal medicine (155/210, 74%) and non internal medicine departments (18/38, 47%) (p=.001). The most common reasons for a diagnosis being judged as not valid were: insufficient patient data available in 33 patients (13%), symptoms only including abdominal pain/discomfort or abnormal bowel habit in 19 patients (8%), an obvious misuse of the diagnosis in 12 patients (5%) and too short duration of symptoms in 11 cases (4%). Conclusion: The use of the ICD-10 diagnostic code for IBS in Swedish secondary and tertiary care has a high validity in departments of internal medicine but less so in other departments. This finding needs to be addressed when planning and interpreting epidemiologic studies of IBS. Su2090 Colonization of a Novel Lachnospiraceae Bacterium, Isolated From Hyperglycemic Obese Mice, Induces Metabolic Syndrome in Gnotobiotic Mice in Association With Escherichia coli Keishi Kameyama, Kikuji Itoh, Takayoshi Fujii, Sachiko Nishikawa, Takayuki Kajiura, Eiji Nakamura Background and aim: Recent findings suggest that gut microbiota is associated with the development of metabolic syndrome such as obesity and diabetes. However, the existence of specific bacteria in the gut microbiota that cause these metabolic diseases is still controver- sial. The purpose of this study was to identify the specific bacteria which induce metabolic syndrome in mice. Method: Study 1: The gut microbiota pattern in fecal sample was analyzed by terminal restriction fragment length polymorphism (T-RFLP) method and fasting blood glucose levels were determined in individual ob/ob mice (genetically deficient in leptin). Study 2: We distinguished a T-RF size which was observed to be characteristic in hyperglyce- mic mice. Then the bacterium possessing the characteristic T-RF size was isolated from the mice and identification of the bacterium was done by sequencing of the 16S rRNA gene (16S rDNA). Study 3: We produced the gnotobiotic high fat diet-induced obese (HF-DIO) or normal mice (C57BL/6J) colonized both with the isolated bacterium and Escherichia coli for 10 weeks and then observed the changes of metabolic phenotypes of the mice. Study 4: qPCR analysis targeted for the mice characteristic bacterial species was performed using fecal samples from human volunteer with or without type 2 diabetes (T2D). Results: ob/ ob mice showed interindividual differences in gut microbiota and fasting blood glucose levels. T-RFLP analysis revealed that the T-RF size of 282 bp was typical in the hyperglycemic ob/ob mice. We succeeded in isolating the bacterium possessing T-RF 282 bp and identified as a new member of Lachnospiraceae (strain ID: AJ110941). To confirm the pathogenic role of AJ110941 in the induction of hyperglycemia, we produced HF-DIO and normal gnotobiotic mice colonized with the AJ110941 and E. coli. The colonization of AJ110941 caused signifi- cant increases in body weight, mesenteric adipose tissue weight and plasma insulin level, and a significant decrease in plasma insulin-sensitivity, in both HF-DIO and normal gnotobi- otic mice. Especially, HF-DIO gnotobiotic mice showed a significant decrease in plasma adiponectin level in colonization with AJ110941. Interestingly, human fecal sample analysis revealed that the prevalence rate of AJ110941 colonization in T2D subjects was two-times higher (71%) compared with healthy subjects (38%) in Japanese (30 subjects in each group). 16S rDNA copies of AJ110941 were more significantly presented in fecal samples of T2D subject than healthy subjects. Conclusion: These results clearly indicate that AJ110941 should be one of the important causative gut microbiota for the induction of obesity and insulin resistance in mice, and possibly in human. These findings would explore new directions for the diagnosis, treatment and prevention of metabolic syndrome by regulating the bacteria in the gut. S-543 AGA Abstracts Su2091 Differential Response to Anticoagulation in Germ-Free Swiss Webster Mice Conventionalized With Fecal Transplantation From Human Donors Requiring Varying Doses of Warfarin Philip Chuang, Emily Walsh, SuBin Kim, Tae Lee, John I. Hwang, Ilseung Cho Background: Warfarin is a commonly used anticoagulant for patients at risk for thromboem- bolic disease. However, its narrow therapeutic range, dosing variability and the consequences of under- or overdosing make it difficult to administer. Because warfarin reduces vitamin K to activate clotting factors, differences in gut microbial vitamin K2 production may contribute to inter-individual variations in dose response. Recent studies suggest that the human gut microbiome may convey transmissible metabolic characteristics to a number of disease states. We hypothesized that the dose response of germ-free mice conventionalized with stool samples from human donors with low- or high-dose warfarin requirements would mimic the dose response of their human donors. Methods: Stool samples were collected from two patients at the Manhattan campus of the New York Harbor Healthcare System gastroenterology clinic: one patient was on low-dose warfarin (11 mg weekly) and the second on high dose warfarin (60 mg weekly). Donor stool was suspended in anaerobic culture media, homogenized, and filtered through a BD Falcon 100 um cell strainer for delivery to mice by oral gavage. Twenty 4-week old, Swiss Webster germ-free mice were divided into four cohorts of five mice; two cohorts received stool from the low-dose warfarin donor (warfarin sensitive) and two from the high-dose donor (warfarin resistant). Mice were observed for 40 days to allow for colonization and stabilization of gut microbiota. Daily fecal pellets were collected from all mice. Baseline International Normalized Ratios (INRs) were obtained at day 41 using the Roche CoaguChek XS system, which has a functional range of 0.8 to 8.0. Mice were then orally gavaged with 0.5 mg/ml of warfarin in ethanol at a dose of 1.0 mg/kg/day for three days followed by a repeat INR assessment on day 45. Results: Two mice were lost from each cohort due to aspiration and/or bleeding side-effects of warfarin. The baseline INRs of the two ‘warfarin-sensitive' cohorts and the two ‘warfarin resistant' cohorts ranged from 0.8-0.9 and <0.8-0.8, respectively. After warfarin dosing, the ‘warfarin sensitive' cohorts demonstrated consistently elevated INRs (mean > 8.0) as did one cage cohort transplanted with warfarin-resistant donor stool (mean > 8.0). The second ‘warfarin-resistant' cage cohort, however, demonstrated significantly lower INRs (mean = 2.13, p<0.01) than the warfarin sensitive cohort. Conclusions: The generation of a warfarin- resistant mouse phenotype in one cage cohort after fecal transplant from warfarin-resistant human donors indicates that the dose response of warfarin is a transmissible characteristic of the gut microbiome. Delineating the effects of the microbiome on the efficacy and dosing of medications may improve clinical endpoints and safety. Response to warfarin in germ-free Swiss Webster mice conventionalized with fecal transplant from human donors. Germ-free Swiss Webster mice were conventionalized with fecal trans- plant from donors requiring either high (warfarin-resistant) or low (warfarin-sensitive) doses of warfarin for clinical anticoagulation. After dosing with warfarin at 1.0mg/kg/day, the warfarin-resistant cohort had significantly lower INR measurements than the warfarin-sensi- tive cohort (p<0.05). Su2092 A High Fat Lower Fiber Dietary Intervention Perturbs the Urinary Metabonome and Gut Microbial Co-Metabolic Processes in a Population of African and African Americans James Kinross, Jia Li, Leo Lahti, Junhai Ou, Franck Carbonero, Kishore Vipperla, Elizabeth H. Ruder, Keith Newton, Vasudevan G. Naidoo, James P. DeLany, Erwin G. Zoetendal, H. Rex Gaskins, Stephen J. O'Keefe, Jeremy K. Nicholson Background: The dietary-gut microbiome axis plays an important role in the definition of an individuals colon cancer risk, however this mechanism has yet to be fully resolved. Methods: We analyzed metabolic profiles and gut microbial co-metabolic metabolites in a prospective dietary intervention study in a population of African American (AA) and Africans (AF). Twenty African and twelve African American healthy middle-age volunteers were recruited and subjected to strictly controlled home environments (HE) for two weeks. The AF cohort was provided with food containing 51% fat, 27% proteins, 20% carbohydrates and 3 g fiber/1000 kcals, and the AA group received diet with 17% fat, 15% proteins, 68% carbohydrates and 21 g fiber/1000 kcals. Fecal samples were collected from volunteers after 2-weeks of a HE control period and after 2-weeks of the dietary intervention (DI). 600MHz 1H Nuclear Magnetic Resonance (NMR) spectroscopy was used to acquire fecal metabolic profiles and multivariate statistical data analyses including orthogonal-partial least squares regression analysis (OPLS) were applied. Results: The horizontal pair-wise comparisons of AA and AF using OPLS-DA (R2X=29.8%, Q2Y=0.59) demonstrated that the AF group exhibited higher levels of uracil, hypoxanthine, phenylacetate, tyrosine, glycine, short chain fatty acids (SCFAs, e.g. acetate, propionate, valerate, butyrate), branched chain amino acids (leucine, isoleucine and valine) and lower levels of choline compared with the AA group at the HE time point. Elevated levels of SCFAs and lower concentrations of choline suggest AGA Abstracts