- Email: [email protected]
Bile Acid Diarrhea: Patient-Reported Symptoms and Outcomes
longer significant. At enterotype level, 27% of individuals which were Bacteroides at baseline shifted towards the Ruminococcus enterotype, 11% of Ruminococcus shifted towards Bacteroides and no shifts were observed in the Prevotella enterotype. Conclusion: The FIT diet significantly increased intestinal microbial richness in healthy individuals, especially in individuals with low-richness at baseline. The Bacteroides enterotype, frequently associated with dysbiosis, was less resilient to dietary changes. Furthermore, a significant decrease in fecal calprotectin was seen after the diet suggesting additional anti-inflammatory metabolic effects beyond microbial richness and composition. A proof-of-concept study using the FIT diet is currently ongoing in patients with quiescent ulcerative colitis but recent flare, to see if the diet could prevent relapse.
DIETARY PATTERNS AND MUCOSA ASSOCIATED COLONIC BACTERIAL MICROBIOTA AND STOOL MICROBIOTA IN HEALTHY SUBJECTS Natasha Shah, Prachi S. Chakradeo, Phillip Engen, Ali Keshavarzian, Ece Mutlu Links between gut microbiome composition and diet have been reported in small crosssectional studies in the past. There are no studies that have examined longitudinal diet correlations with gut microbiome composition. In this study, we examined correlations between gut microbiome composition in mucosal biopsies as well as stool samples and diet in 9 healthy subjects over a 9 month period. Healthy subjects (n=9), recruited from the community, underwent 4 unprepped flexible sigmoidoscopies at 0, 3, 6, and 9 months during which biopsies were taken of the normal colonic mucosa. Stool samples were collected within 24 hours of the biopsies. Samples were sequenced using 16S rDNA on a 454 Roche Titanium platform, filtered for quality/chimeras, and were analyzed using Qiime. At each visit, the subjects completed the standardized NIH Dietary History Questionnaire (DHQ) version 1. Nutrient intake was adjusted for calories using a residual model. Spearman correlations were calculated between the reported nutrient intake and predominant bacterial phyla Bacteriodetes, Firmicutes, and Proteobacteria using SPSS. Bacteriodetes in biopsy and stool samples was positively associated with vegetable servings (r=0.374, p=0.03 and r= 0.519, p=0.002, respectively); in biopsy samples only with dry beans and potato (r=0.47, p=0.005) and white potato intake (r=0.509, p=0.002). Monosaturated fat intake (r=0.354, p=0.04), and total protein intake (r=0.350, p=0.040) also positively correlated with Bacteroidetes in mucosal biopsies in stool samples. Bacteriodetes in biopsy samples was negatively associated with intakes of vitamin B12 (r=0.412, p=0.016), iron (r=-0.375, p=0.029), and zinc (r=--0.367, p=0.003). Firmicutes in biopsy and stool samples were positively associated with whole grain servings (r=0.427, p=0.12 and r=0.352, p=0.041, respectively). Firmicutes in stool was negatively associated with protein intake (r=-0.385, p=0.024) and vegetable servings samples (r=-0.344, p=0.046). Firmicutes in biopsy samples positively associated with intake of iron (r=0.372, p=0.030), and zinc (r=0.398, p=0.040). Proteobacteria in mucosal biopsies positively associated with cholesterol intake (r=0.457, p=0.007), eggs (r= 0.428, p=0.011), and animal meat intake specifically poultry and fish (r=0.379, p=0.030) and beef and pork (r=0.386, p=0.024), and were negatively associated with dark green vegetables (r=-0.355, p=0.040), magnesium(r =-0.338, p=0.050) and vitamin C intake (r=0.039, p=0.043). Dietary intake appears to be associated with changes in bacterial phyla abundance, suggesting that macro and micronutrient intake likely plays a role in the temporal variations in gut microbiota composition. The majority of nutrients tended to be either positively or negatively associated within the three abundant phyla in the mucosal surface and stool samples with some exceptions.
1 A NOVEL MULTI-MATRIX FORMULATION OF THE BROAD-SPECTRUM, POORLY ABSORBED ANTIBIOTIC RIFAMYCIN SV IS EQUALLY EFFECTIVE AS SYSTEMIC CIPROFLOXACIN IN THE ORAL TREATMENT OF TRAVELERS' DIARRHEA: A DOUBLE-BLIND, DOUBLE-DUMMY, MULTICENTRE, RANDOMIZED STUDY Robert Steffen, Herbert L. DuPont, Zhi-Dong Jiang, Prithi de Sousa Araujo, Monica L. Gracias Garcia, Tanju Nacak, Roland Greinwald BACKGROUND: Travelers' Diarrhea (TD) remains the most common health problem experienced by travellers visiting lower income regions of the world (Steffen et al., 2015). TD affects about 24 to 40 million people worldwide each year. As treatment is typically selfadministrated while abroad, it is important treatment is effective, safe and easy to use. The new oral multi-matrix formulation Rifamycin SV-MMX®, which ensures targeted delivery of the antibiotic to the colon, proved to be superior to placebo in treating TD (DuPont et al., 2014). AIMS: This pivotal study aimed to compare the efficacy and safety of Rifamycin SV-MMX® 400 mg twice daily (RIF) versus Ciprofloxacin 500 mg twice daily (CIP) in the oral treatment of TD. METHODS: International travelers visiting India, Guatemala or Ecuador and presenting within 72 h of TD onset (defined as at least 3 unformed stools within 24h accompanied by symptoms), were randomized to receive a 3-day treatment with RIF or CIP. Patients documented symptoms through day 5. Stools samples for microbiological evaluation were collected at baseline visit and end of treatment visit. Primary endpoint was time to last unformed stool (TLUS), defined as the interval in hours between the first dose of study drug and the last unformed stool passed, after which clinical cure was declared. RESULTS: A total of 835 patients were randomized (India: 805, Latin America: 30) and considered for the safety (SAF) and full analysis set (FAS). Mean age was 40.2 years, 49.3% were female, 82.2% Caucasian and 85.5% tourists. Most patients presented at baseline with moderate symptoms (78.7%) or severe symptoms (21.2%). In 62.3% of the patients, at least one pathogen was detected at baseline and 23.7% had multiple pathogens. Diarrheagenic enterotoxigenic E.coli was the most common pathogen. A total of 767 patients contributed to the PP population for confirmatory final analysis. Median TLUS in the RIF group was 42.8 h vs. 36.8 h in the CIP group indicating non-inferiority of Rifamycin SV-MMX® to Ciprofloxacin in regard to the primary endpoint TLUS (p = 0.0035). Results from the secondary efficacy endpoints fully confirmed the results of the primary analysis indicating equal clinical efficacy for both compounds (Table 1). Microbiological cure rate was similar in both groups (RIF: 57.2%; CIP: 55.5%). Both drugs were well tolerated. In total, 102/ 835 patients (12.2%) experienced at least 1 treatment-emergent AE within the scope of this study (RIF: 52 patients; CIP: 50 patients). CONCLUSION: The novel multi-matrix formulation of the broad-spectrum, poorly absorbed antibiotic Rifamycin SV was non-inferior to the systemic antibiotic Ciprofloxacin in the oral treatment of TD, giving patients a new effective and safe treatment option. REFERENCES: Steffen R et al. JAMA. 2015; 313:7180. DuPont HL et al. J Travel Med. 2014; 21:369-76. Results from clinical efficacy endpoints (FAS)
1b THERAPEUTIC MANIPULATION OF THE GUT MICROBIOTA THROUGH DIET TO REDUCE INTESTINAL INFLAMMATION: RESULTS FROM THE FIT TRIAL João Sabino, Sara Vieira-Silva, Kathleen Machiels, Marie Joossens, Gwen Falony, Marc Ferrante, Gert A. Van Assche, Schalk Van Der Merwe, Christophe Matthys, Jeroen Raes, Severine Vermeire 2 Background: The intestinal microbiota is implicated in the pathogenesis of several immunemediated disorders including inflammatory bowel diseases and has subsequently been the target of different therapeutic interventions, such as fecal microbiota transplantation, pro-, pre- and antibiotics. We designed the Food influence on the Intestinal microbioTa (FIT) trial to study the effects of diet on intestinal microbiota changes and inflammation in healthy individuals (part 1) and patients with ulcerative colitis (part 2). We here report the results of the first part of the study. Methods: The FIT diet consists of a semi-vegetarian diet, high in fiber (>30g/day), low in saturated fat and sulphites and exclusion of added sugar, processed foods, carrageenan, and polysorbate-80. Following informed consent, 29 volunteers followed the diet for 1 month and were followed up for 6 months. Fecal calprotectin was measured on fresh fecal samples (Bühlmann ELISA). Dietary compliance was followed with food frequency questionnaires and 3-day food records. 16S rDNA paired-end sequencing targeting the V4 hypervariable region was performed using Illumina MiSeq sequencer. Sequencing depth was downsized to 10000 reads/sample. The RDP classifier was used for taxonomic annotation. Statistical analyses were performed with R. Results: A significant weight loss was observed after 4 weeks following the FIT diet (t-test, p<0.0001, mean -2.3 Kg, SD -1.5). Strikingly, fecal calprotectin - although within normal ranges in all but 1 individual significantly decreased after dietary intervention (Wilcoxon test, p=0.0008) and microbial richness significantly increased (OTU observed richness, Wilcoxon test, p=0.004). There was an inverse correlation between the microbial richness at baseline and the magnitude of increase in richness following the diet (Spearman rho -0.51, p=0.0113). At genus level, Roseburia decreased after the diet, although after multiple testing correction, this was no
BILE ACID DIARRHEA: PATIENT-REPORTED SYMPTOMS AND OUTCOMES Julian R. Walters, Ayman Bannaga, Michelle O'Connor, Lawrence Kelman, Claire Pitchford, Ramesh Arasaradnam Introduction: Bile salt malabsorption/bile acid diarrhea is increasingly being recognized as a cause of persistent, chronic diarrhea and other related bowel symptoms, but patients often receive suboptimal treatment as medical and public awareness of the condition is poor. Patient support groups have been established recently and they conducted an online survey to provide information on how this condition affects patients and to help with dealings with medical practitioners. Methods: Members of the Bile Salt Malabsorption Facebook Group (membership >1300) and BAM Support UK were invited to complete an online survey in November 2015. The first 100 responses were analyzed. Results: 91% of the respondents were female, 80% were from the UK with a wide age range. 89% had already received a diagnosis of the condition, with 62% having had a SeHCAT scan; others had been diagnosed by history or by therapeutic trial. Over 35% were diagnosed after the age of 50. 38% had Type 2 (idiopathic, primary) and 37% type 3 (including post-cholecystectomy). 59% reported undergoing more than two tests before being diagnosed. Symptoms had been present for >5 years before diagnosis in over half. These symptoms included explosive, offensive, smelly or watery diarrhea ("always" or "mostly") in 80%, urgency in 85%, abdominal swelling/ bloating in 54%, pain in 59%, at least occasional incontinence in 88%, and also wind and tiredness. Treatment significantly improved symptoms in around 60% so that only 17% then experienced diarrhea as "always"/"mostly" (p<0.001 Fisher's exact test). A reduction
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in urgency was found, being experienced "occasionally" in 51% (p<0.001). Cholestyramine was the only drug used in 50%. Many patients were on colesevelam or other medications. Mental health issues included embarrassment ("often" /"sometimes" in >90%), nervousness leaving home (>90%), depression, isolation, helplessness and low self-esteem (all >80%), which improved with treatment. Diet avoidances, especially fat and lactose, were common (in 78%) and so was weight gain. 75% were now under continuing medical care and most were satisfied with this. Respondents had seen multiple practitioners before diagnosis but felt they were not taken seriously (35%) or dismissed (50%), had seen GPs who were unaware of the condition (28%) or were told nothing could be done (39%). Two-thirds had previously been given a diagnosis of IBS. 68% had >10 interactions with medical professionals before being diagnosed with bile acid diarrhea. Conclusion: Patient-reported issues in bile acid diarrhea include a long history of bowel and mental health symptoms before the correct diagnosis was made. Poor awareness of the condition by medical practitioners was common but treatment resulted in significant improvement.
Multivariable analysis of factors independently associated with a positive stool pathogen PCR test.
3 PREVALENCE AND DISTRIBUTION OF GASTROINTESTINAL PATHOGENS IN PATIENTS WITH AND WITHOUT IMMUNE-BASED LUMINAL DISORDERS: A RETROSPECTIVE COHORT STUDY USING A NEW MULTIPATHOGEN STOOL PCR TEST Yael Nobel, Jordan Axelrad, Susan Whittier, Garrett Lawlor, Simon Lichtiger, Peter H. R. Green, Benjamin Lebwohl Background: New clinical PCR-based tests can identify GI pathogens with a high degree of sensitivity and accuracy. Immune-mediated GI diseases (inflammatory bowel disease [IBD] and celiac disease [CD]) are associated with alterations in both gut microbial composition and systemic immunity, and patients with IBD/CD have increased risk of infection with a variety of intestinal and non-intestinal pathogens. PCR-based stool tests have not yet been utilized to compare rates of specific GI pathogens in patients with diarrheal illness. Methods: All adults who underwent outpatient stool gastrointestinal pathogen testing for evaluation of altered bowel habits at our institution from January 1 to December 31, 2015 were assessed retrospectively. Sites included offices, the emergency department, and the endoscopy unit. All samples had been analyzed with the FilmArray Gastrointestinal Panel (BioFire Diagnostics, Salt Lake City, UT) for the presence of 21 bacterial, parasitic, and viral pathogens. Results: Of 955 patients, 127 (13%) had an immune-based disorder: 63 with IBD, 60 with CD, and 4 with a dual IBD-CD diagnosis. Among 337 total patients with positive tests, 465 bacterial, parasitic, or viral pathogens were identified, of which combined E. coli species accounted for 296/465 (64%). A positive test (presence of any pathogen) was found in 29/127 patients (23%) with IBD/CD, compared to 308/828 patients (37%) without (p<0.01). On multivariate analysis (see Table), any positive test result was significantly less likely with IBD/CD diagnosis (OR 0.49; 95%CI 0.31-0.77) and significantly more likely with male gender (OR 1.44; 95%CI 1.10-1.90) and emergency department location (OR 1.58; 95%CI 1.04-2.40). For each individual pathogen, prevalence was not significantly different in patients with IBD/ CD compared to those without. Analysis of IBD and CD separately did not alter findings. However, when assessed by microbe type, patients with IBD/CD had significantly fewer identified viruses than those without (2% vs. 8% of patients; p=0.01) and parasites (0% vs. 27%; p=0.04), but reduction in identified bacteria did not meet significance (21% vs. 29%; p=0.06). Conclusions: Among 955 outpatients, patients with IBD/CD were significantly less likely than those without to have a pathogen identified as a cause of diarrhea, with significance driven by reduction in viral or parasitic, not bacterial, pathogens. These preliminary findings may be consistent with altered adaptive immunity as a contributor to GI infections in patients with IBD/CD.
4 ADULT AUTOIMMUNE ENTEROPATHY MIMICS REFRACTORY CELIAC DISEASE TYPE I IN PRESENTATION AND RESPONSE TO OPEN BUDESONIDE Ayush Sharma, Rok Seon Choung, Tsung-Teh Wu, Pierre Russo, Vandana Nehra, Joseph A. Murray Background and Aims: Autoimmune enteropathy (AIE) is a rare cause of refractory diarrhea in adults that does not respond to any dietary modifications. Adult AIE is often misdiagnosed as refractory celiac disease type I (RCD I) with needless imposition and continuation of a gluten free diet. We performed a case series comparing the demographic and clinical profile of patients with adult AIE and RCD I. We also studied the effects of treating these patients with open capsule budesonide (OB). Methods: A retrospective review of patients diagnosed with adult onset AIE at our institution from January 1, 2000 to January 1, 2016 was performed. We compared this with group of RCD I patients. Open capsule budesonide was used to enable topical distribution of budesonide to the proximal small intestine by the following strategy: 1) first capsule: open the capsule, empty the contents in apple sauce and grind between the teeth and swallow; 2) second capsule: open the capsule, empty the contents in apple sauce and swallow; 3) swallow the whole capsule. Demographics, clinical features, histopathological findings, and treatments and outcomes were abstracted for the current analysis. Results: A total of 69 patients were included; 26 adult AIE and 43 RCD I (Table I). The mean age at diagnosis was significantly higher in patients with RCD I than adult AIE (60 years vs 44 years; p=.003). There was a significant difference in gender between adult AIE and RCD I patients (male: 62% vs 28%; p=.005). There was no significant difference in the mean BMI of patients with adult AIE patients and RCD I (21.9 vs 23.2; p=.21). Adult AIE patients presented more often with diarrhea and fatigue than the RCD I patients (p= 0.001). Total parenteral nutrition was required more often in adult AIE patients than the RCD I patients (35% vs 7%; p=0.03). Gut epithelial cell antibodies were more commonly positive in adult AIE (85%) than in RCD I patients (12%) (p=<0.001). Hypoalbuminemia was more often found in adult AIE patients than RCD I patients (54% vs 16%; p=0.01). On duodenal biopsies, all patients with adult AIE and RCD I had a certain degree of villous atrophy with no significant difference between the two (p=0.18). Patients with adult AIE and RCD I were often treated with systemic steroids, but only 11% and 4% of them (few patients) responded clinically. After the failure of systemic steroid therapy, the OB treatment was given to all RCD I (100%) patients and majority (77%) adult AIE patients. Majority of adult AIE (75%) responded to OB therapy and nearly all (92%) patients with RCD I also responded (Table II). Conclusion: Adult AIE may mimic but often exceeds the symptomatic severity of RCD I. Topical potent steroid therapy seems to be just as efficacious in adult AIE as in RCD I patients, achieving clinical resolution in most patients.
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DIETARY PATTERNS AND MUCOSA ASSOCIATED COLONIC BACTERIAL MICROBIOTA AND STOOL MICROBIOTA IN HEALTHY SUBJECTS Natasha Shah, Prachi S. Chakradeo, Phillip Engen, Ali Keshavarzian, Ece Mutlu Links between gut microbiome composition and diet have been reported in small crosssectional studies in the past. There are no studies that have examined longitudinal diet correlations with gut microbiome composition. In this study, we examined correlations between gut microbiome composition in mucosal biopsies as well as stool samples and diet in 9 healthy subjects over a 9 month period. Healthy subjects (n=9), recruited from the community, underwent 4 unprepped flexible sigmoidoscopies at 0, 3, 6, and 9 months during which biopsies were taken of the normal colonic mucosa. Stool samples were collected within 24 hours of the biopsies. Samples were sequenced using 16S rDNA on a 454 Roche Titanium platform, filtered for quality/chimeras, and were analyzed using Qiime. At each visit, the subjects completed the standardized NIH Dietary History Questionnaire (DHQ) version 1. Nutrient intake was adjusted for calories using a residual model. Spearman correlations were calculated between the reported nutrient intake and predominant bacterial phyla Bacteriodetes, Firmicutes, and Proteobacteria using SPSS. Bacteriodetes in biopsy and stool samples was positively associated with vegetable servings (r=0.374, p=0.03 and r= 0.519, p=0.002, respectively); in biopsy samples only with dry beans and potato (r=0.47, p=0.005) and white potato intake (r=0.509, p=0.002). Monosaturated fat intake (r=0.354, p=0.04), and total protein intake (r=0.350, p=0.040) also positively correlated with Bacteroidetes in mucosal biopsies in stool samples. Bacteriodetes in biopsy samples was negatively associated with intakes of vitamin B12 (r=0.412, p=0.016), iron (r=-0.375, p=0.029), and zinc (r=--0.367, p=0.003). Firmicutes in biopsy and stool samples were positively associated with whole grain servings (r=0.427, p=0.12 and r=0.352, p=0.041, respectively). Firmicutes in stool was negatively associated with protein intake (r=-0.385, p=0.024) and vegetable servings samples (r=-0.344, p=0.046). Firmicutes in biopsy samples positively associated with intake of iron (r=0.372, p=0.030), and zinc (r=0.398, p=0.040). Proteobacteria in mucosal biopsies positively associated with cholesterol intake (r=0.457, p=0.007), eggs (r= 0.428, p=0.011), and animal meat intake specifically poultry and fish (r=0.379, p=0.030) and beef and pork (r=0.386, p=0.024), and were negatively associated with dark green vegetables (r=-0.355, p=0.040), magnesium(r =-0.338, p=0.050) and vitamin C intake (r=0.039, p=0.043). Dietary intake appears to be associated with changes in bacterial phyla abundance, suggesting that macro and micronutrient intake likely plays a role in the temporal variations in gut microbiota composition. The majority of nutrients tended to be either positively or negatively associated within the three abundant phyla in the mucosal surface and stool samples with some exceptions.
1 A NOVEL MULTI-MATRIX FORMULATION OF THE BROAD-SPECTRUM, POORLY ABSORBED ANTIBIOTIC RIFAMYCIN SV IS EQUALLY EFFECTIVE AS SYSTEMIC CIPROFLOXACIN IN THE ORAL TREATMENT OF TRAVELERS' DIARRHEA: A DOUBLE-BLIND, DOUBLE-DUMMY, MULTICENTRE, RANDOMIZED STUDY Robert Steffen, Herbert L. DuPont, Zhi-Dong Jiang, Prithi de Sousa Araujo, Monica L. Gracias Garcia, Tanju Nacak, Roland Greinwald BACKGROUND: Travelers' Diarrhea (TD) remains the most common health problem experienced by travellers visiting lower income regions of the world (Steffen et al., 2015). TD affects about 24 to 40 million people worldwide each year. As treatment is typically selfadministrated while abroad, it is important treatment is effective, safe and easy to use. The new oral multi-matrix formulation Rifamycin SV-MMX®, which ensures targeted delivery of the antibiotic to the colon, proved to be superior to placebo in treating TD (DuPont et al., 2014). AIMS: This pivotal study aimed to compare the efficacy and safety of Rifamycin SV-MMX® 400 mg twice daily (RIF) versus Ciprofloxacin 500 mg twice daily (CIP) in the oral treatment of TD. METHODS: International travelers visiting India, Guatemala or Ecuador and presenting within 72 h of TD onset (defined as at least 3 unformed stools within 24h accompanied by symptoms), were randomized to receive a 3-day treatment with RIF or CIP. Patients documented symptoms through day 5. Stools samples for microbiological evaluation were collected at baseline visit and end of treatment visit. Primary endpoint was time to last unformed stool (TLUS), defined as the interval in hours between the first dose of study drug and the last unformed stool passed, after which clinical cure was declared. RESULTS: A total of 835 patients were randomized (India: 805, Latin America: 30) and considered for the safety (SAF) and full analysis set (FAS). Mean age was 40.2 years, 49.3% were female, 82.2% Caucasian and 85.5% tourists. Most patients presented at baseline with moderate symptoms (78.7%) or severe symptoms (21.2%). In 62.3% of the patients, at least one pathogen was detected at baseline and 23.7% had multiple pathogens. Diarrheagenic enterotoxigenic E.coli was the most common pathogen. A total of 767 patients contributed to the PP population for confirmatory final analysis. Median TLUS in the RIF group was 42.8 h vs. 36.8 h in the CIP group indicating non-inferiority of Rifamycin SV-MMX® to Ciprofloxacin in regard to the primary endpoint TLUS (p = 0.0035). Results from the secondary efficacy endpoints fully confirmed the results of the primary analysis indicating equal clinical efficacy for both compounds (Table 1). Microbiological cure rate was similar in both groups (RIF: 57.2%; CIP: 55.5%). Both drugs were well tolerated. In total, 102/ 835 patients (12.2%) experienced at least 1 treatment-emergent AE within the scope of this study (RIF: 52 patients; CIP: 50 patients). CONCLUSION: The novel multi-matrix formulation of the broad-spectrum, poorly absorbed antibiotic Rifamycin SV was non-inferior to the systemic antibiotic Ciprofloxacin in the oral treatment of TD, giving patients a new effective and safe treatment option. REFERENCES: Steffen R et al. JAMA. 2015; 313:7180. DuPont HL et al. J Travel Med. 2014; 21:369-76. Results from clinical efficacy endpoints (FAS)
1b THERAPEUTIC MANIPULATION OF THE GUT MICROBIOTA THROUGH DIET TO REDUCE INTESTINAL INFLAMMATION: RESULTS FROM THE FIT TRIAL João Sabino, Sara Vieira-Silva, Kathleen Machiels, Marie Joossens, Gwen Falony, Marc Ferrante, Gert A. Van Assche, Schalk Van Der Merwe, Christophe Matthys, Jeroen Raes, Severine Vermeire 2 Background: The intestinal microbiota is implicated in the pathogenesis of several immunemediated disorders including inflammatory bowel diseases and has subsequently been the target of different therapeutic interventions, such as fecal microbiota transplantation, pro-, pre- and antibiotics. We designed the Food influence on the Intestinal microbioTa (FIT) trial to study the effects of diet on intestinal microbiota changes and inflammation in healthy individuals (part 1) and patients with ulcerative colitis (part 2). We here report the results of the first part of the study. Methods: The FIT diet consists of a semi-vegetarian diet, high in fiber (>30g/day), low in saturated fat and sulphites and exclusion of added sugar, processed foods, carrageenan, and polysorbate-80. Following informed consent, 29 volunteers followed the diet for 1 month and were followed up for 6 months. Fecal calprotectin was measured on fresh fecal samples (Bühlmann ELISA). Dietary compliance was followed with food frequency questionnaires and 3-day food records. 16S rDNA paired-end sequencing targeting the V4 hypervariable region was performed using Illumina MiSeq sequencer. Sequencing depth was downsized to 10000 reads/sample. The RDP classifier was used for taxonomic annotation. Statistical analyses were performed with R. Results: A significant weight loss was observed after 4 weeks following the FIT diet (t-test, p<0.0001, mean -2.3 Kg, SD -1.5). Strikingly, fecal calprotectin - although within normal ranges in all but 1 individual significantly decreased after dietary intervention (Wilcoxon test, p=0.0008) and microbial richness significantly increased (OTU observed richness, Wilcoxon test, p=0.004). There was an inverse correlation between the microbial richness at baseline and the magnitude of increase in richness following the diet (Spearman rho -0.51, p=0.0113). At genus level, Roseburia decreased after the diet, although after multiple testing correction, this was no
BILE ACID DIARRHEA: PATIENT-REPORTED SYMPTOMS AND OUTCOMES Julian R. Walters, Ayman Bannaga, Michelle O'Connor, Lawrence Kelman, Claire Pitchford, Ramesh Arasaradnam Introduction: Bile salt malabsorption/bile acid diarrhea is increasingly being recognized as a cause of persistent, chronic diarrhea and other related bowel symptoms, but patients often receive suboptimal treatment as medical and public awareness of the condition is poor. Patient support groups have been established recently and they conducted an online survey to provide information on how this condition affects patients and to help with dealings with medical practitioners. Methods: Members of the Bile Salt Malabsorption Facebook Group (membership >1300) and BAM Support UK were invited to complete an online survey in November 2015. The first 100 responses were analyzed. Results: 91% of the respondents were female, 80% were from the UK with a wide age range. 89% had already received a diagnosis of the condition, with 62% having had a SeHCAT scan; others had been diagnosed by history or by therapeutic trial. Over 35% were diagnosed after the age of 50. 38% had Type 2 (idiopathic, primary) and 37% type 3 (including post-cholecystectomy). 59% reported undergoing more than two tests before being diagnosed. Symptoms had been present for >5 years before diagnosis in over half. These symptoms included explosive, offensive, smelly or watery diarrhea ("always" or "mostly") in 80%, urgency in 85%, abdominal swelling/ bloating in 54%, pain in 59%, at least occasional incontinence in 88%, and also wind and tiredness. Treatment significantly improved symptoms in around 60% so that only 17% then experienced diarrhea as "always"/"mostly" (p<0.001 Fisher's exact test). A reduction
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in urgency was found, being experienced "occasionally" in 51% (p<0.001). Cholestyramine was the only drug used in 50%. Many patients were on colesevelam or other medications. Mental health issues included embarrassment ("often" /"sometimes" in >90%), nervousness leaving home (>90%), depression, isolation, helplessness and low self-esteem (all >80%), which improved with treatment. Diet avoidances, especially fat and lactose, were common (in 78%) and so was weight gain. 75% were now under continuing medical care and most were satisfied with this. Respondents had seen multiple practitioners before diagnosis but felt they were not taken seriously (35%) or dismissed (50%), had seen GPs who were unaware of the condition (28%) or were told nothing could be done (39%). Two-thirds had previously been given a diagnosis of IBS. 68% had >10 interactions with medical professionals before being diagnosed with bile acid diarrhea. Conclusion: Patient-reported issues in bile acid diarrhea include a long history of bowel and mental health symptoms before the correct diagnosis was made. Poor awareness of the condition by medical practitioners was common but treatment resulted in significant improvement.
Multivariable analysis of factors independently associated with a positive stool pathogen PCR test.
3 PREVALENCE AND DISTRIBUTION OF GASTROINTESTINAL PATHOGENS IN PATIENTS WITH AND WITHOUT IMMUNE-BASED LUMINAL DISORDERS: A RETROSPECTIVE COHORT STUDY USING A NEW MULTIPATHOGEN STOOL PCR TEST Yael Nobel, Jordan Axelrad, Susan Whittier, Garrett Lawlor, Simon Lichtiger, Peter H. R. Green, Benjamin Lebwohl Background: New clinical PCR-based tests can identify GI pathogens with a high degree of sensitivity and accuracy. Immune-mediated GI diseases (inflammatory bowel disease [IBD] and celiac disease [CD]) are associated with alterations in both gut microbial composition and systemic immunity, and patients with IBD/CD have increased risk of infection with a variety of intestinal and non-intestinal pathogens. PCR-based stool tests have not yet been utilized to compare rates of specific GI pathogens in patients with diarrheal illness. Methods: All adults who underwent outpatient stool gastrointestinal pathogen testing for evaluation of altered bowel habits at our institution from January 1 to December 31, 2015 were assessed retrospectively. Sites included offices, the emergency department, and the endoscopy unit. All samples had been analyzed with the FilmArray Gastrointestinal Panel (BioFire Diagnostics, Salt Lake City, UT) for the presence of 21 bacterial, parasitic, and viral pathogens. Results: Of 955 patients, 127 (13%) had an immune-based disorder: 63 with IBD, 60 with CD, and 4 with a dual IBD-CD diagnosis. Among 337 total patients with positive tests, 465 bacterial, parasitic, or viral pathogens were identified, of which combined E. coli species accounted for 296/465 (64%). A positive test (presence of any pathogen) was found in 29/127 patients (23%) with IBD/CD, compared to 308/828 patients (37%) without (p<0.01). On multivariate analysis (see Table), any positive test result was significantly less likely with IBD/CD diagnosis (OR 0.49; 95%CI 0.31-0.77) and significantly more likely with male gender (OR 1.44; 95%CI 1.10-1.90) and emergency department location (OR 1.58; 95%CI 1.04-2.40). For each individual pathogen, prevalence was not significantly different in patients with IBD/ CD compared to those without. Analysis of IBD and CD separately did not alter findings. However, when assessed by microbe type, patients with IBD/CD had significantly fewer identified viruses than those without (2% vs. 8% of patients; p=0.01) and parasites (0% vs. 27%; p=0.04), but reduction in identified bacteria did not meet significance (21% vs. 29%; p=0.06). Conclusions: Among 955 outpatients, patients with IBD/CD were significantly less likely than those without to have a pathogen identified as a cause of diarrhea, with significance driven by reduction in viral or parasitic, not bacterial, pathogens. These preliminary findings may be consistent with altered adaptive immunity as a contributor to GI infections in patients with IBD/CD.
4 ADULT AUTOIMMUNE ENTEROPATHY MIMICS REFRACTORY CELIAC DISEASE TYPE I IN PRESENTATION AND RESPONSE TO OPEN BUDESONIDE Ayush Sharma, Rok Seon Choung, Tsung-Teh Wu, Pierre Russo, Vandana Nehra, Joseph A. Murray Background and Aims: Autoimmune enteropathy (AIE) is a rare cause of refractory diarrhea in adults that does not respond to any dietary modifications. Adult AIE is often misdiagnosed as refractory celiac disease type I (RCD I) with needless imposition and continuation of a gluten free diet. We performed a case series comparing the demographic and clinical profile of patients with adult AIE and RCD I. We also studied the effects of treating these patients with open capsule budesonide (OB). Methods: A retrospective review of patients diagnosed with adult onset AIE at our institution from January 1, 2000 to January 1, 2016 was performed. We compared this with group of RCD I patients. Open capsule budesonide was used to enable topical distribution of budesonide to the proximal small intestine by the following strategy: 1) first capsule: open the capsule, empty the contents in apple sauce and grind between the teeth and swallow; 2) second capsule: open the capsule, empty the contents in apple sauce and swallow; 3) swallow the whole capsule. Demographics, clinical features, histopathological findings, and treatments and outcomes were abstracted for the current analysis. Results: A total of 69 patients were included; 26 adult AIE and 43 RCD I (Table I). The mean age at diagnosis was significantly higher in patients with RCD I than adult AIE (60 years vs 44 years; p=.003). There was a significant difference in gender between adult AIE and RCD I patients (male: 62% vs 28%; p=.005). There was no significant difference in the mean BMI of patients with adult AIE patients and RCD I (21.9 vs 23.2; p=.21). Adult AIE patients presented more often with diarrhea and fatigue than the RCD I patients (p= 0.001). Total parenteral nutrition was required more often in adult AIE patients than the RCD I patients (35% vs 7%; p=0.03). Gut epithelial cell antibodies were more commonly positive in adult AIE (85%) than in RCD I patients (12%) (p=<0.001). Hypoalbuminemia was more often found in adult AIE patients than RCD I patients (54% vs 16%; p=0.01). On duodenal biopsies, all patients with adult AIE and RCD I had a certain degree of villous atrophy with no significant difference between the two (p=0.18). Patients with adult AIE and RCD I were often treated with systemic steroids, but only 11% and 4% of them (few patients) responded clinically. After the failure of systemic steroid therapy, the OB treatment was given to all RCD I (100%) patients and majority (77%) adult AIE patients. Majority of adult AIE (75%) responded to OB therapy and nearly all (92%) patients with RCD I also responded (Table II). Conclusion: Adult AIE may mimic but often exceeds the symptomatic severity of RCD I. Topical potent steroid therapy seems to be just as efficacious in adult AIE as in RCD I patients, achieving clinical resolution in most patients.
AGA Abstracts
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