Characterization of Proximal Small Intestinal Microbiota in Patients With Suspected Small Intestinal Bacterial Overgrowth: A Cross-Sectional Study

OBJECTIVES: The composition of the small intestinal microbiota has not yet been characterized thoroughly using culture-independent techniques. We compared small intestinal microbial communities in patients with and without small intestinal bacterial overgrowth (SIBO) using culture-dependent and culture-independent bacterial identification approaches. METHODS: Small bowel aspirate and mucosal samples were collected from patients with suspected SIBO. The aspirates were cultured to diagnose SIBO, defined as ≥10 colony-forming units/mL coliform or ≥10 colony-forming units/mL upper aerodigestive tract bacteria. Bacteria in the aspirates and mucosa were identified using 16S rRNA gene sequencing. We compared small intestinal microbiome composition between groups with and without a culture-based SIBO diagnosis. RESULTS: Analysis of the aspirate and mucosal microbial communities from 36 patients revealed decreased α-diversity but no differences in β-diversity in patients with SIBO compared with those without SIBO. There were no significant differences in the relative abundance of individual taxa from the aspirates or mucosa after adjustment for false discovery rate between patients with and without SIBO. Subgroup analysis revealed significant differences in mucosal β-diversity between the coliform and upper aerodigestive tract subgroups. Relative abundances of a mucosal Clostridium spp. (P = 0.05) and an aspirate Granulicatella spp. (P = 0.02) were higher in coliform SIBO vs non-SIBO subgroups. The microbial composition and relative abundance of multiple taxa significantly differed in the mucosal and aspirate specimens. DISCUSSION: Culture-based results of small bowel aspirates do not correspond to aspirate microbiota composition but may be associated with species richness of the mucosal microbiota

Fecal bile acids, fecal short-chain fatty acids, and the intestinal microbiota in patients with irritable bowel syndrome (IBS) and control volunteers

OBJECTIVES/SPECIFIC AIMS: Objectives and goals of this study will be to: (1) compare fecal microbiota and fecal organic acids in irritable bowel syndrome (IBS) patients and controls and (2) investigate the association between colonic transit and fecal microbiota in IBS patients and controls. METHODS/STUDY POPULATION: We propose an investigation of fecal organic acids, colonic transit and fecal microbiota in 36 IBS patients and 18 healthy controls. The target population will be adults ages 18–65 years meeting Rome IV criteria for IBS (both diarrhea- and constipation-predominant, IBS-D and IBS-C) and asymptomatic controls. Exclusion criteria are: (a) history of microscopic colitis, inflammatory bowel disease, celiac disease, visceral cancer, chronic infectious disease, immunodeficiency, uncontrolled thyroid disease, liver disease, or elevated AST/ALT>2.0× the upper limit of normal, (b) prior radiation therapy of the abdomen or abdominal surgeries with the exception of appendectomy or cholecystectomy >6 months before study initiation, (c) ingestion of prescription, over the counter, or herbal medications affecting gastrointestinal transit or study interpretation within 6 months of study initiation for controls or within 2 days before study initiation for IBS patients, (d) pregnant females, (e) antibiotic usage within 3 months before study participation, (f) prebiotic or probiotic usage within the 2 weeks before study initiation, (g) tobacco users. Primary outcomes will be fecal bile acid excretion and profile, short-chain fatty acid excretion and profile, colonic transit, and fecal microbiota. Secondary outcomes will be stool characteristics based on responses to validated bowel diaries. Stool samples will be collected from participants during the last 2 days of a 4-day 100 g fat diet and split into 3 samples for fecal microbiota, SCFA, and bile acid analysis and frozen. Frozen aliquots will be shipped to the Metabolite Profiling Facility at Purdue University and the Mayo Clinic Department of Laboratory Medicine and Pathology for SCFA and bile acid measurements, respectively. Analysis of fecal microbiota will be performed in the research laboratory of Dr David Nelson in collaboration with bioinformatics expertise affiliated with the Nelson lab. Colonic transit time will be measured with the previously validated method using radio-opaque markers. Generalized linear models will be used as the analysis framework for comparing study endpoints among groups. RESULTS/ANTICIPATED RESULTS: This study seeks to examine the innovative concept that specific microbial signatures are associated with increased fecal excretion of organic acids to provide unique insights on a potential mechanistic link between altered intraluminal organic acids and fecal microbiota. DISCUSSION/SIGNIFICANCE OF IMPACT: Results may lead to development of targets for novel therapies and diagnostic biomarkers for IBS, emphasizing the role of the fecal metabolome

Risk factors associated with upper aerodigestive tract or coliform bacterial overgrowth of the small intestine in symptomatic patients

Introduction: The clinical relevance of bacterial types identified in small bowel aspirate cultures during diagnostic evaluation of small intestinal bacterial overgrowth (SIBO) is unclear. Aim: The main purpose of this study was to assess associations between risk factors for upper aerodigestive tract (UAT) or coliform SIBO and SIBO diagnosis by culture. Materials and methods: Small bowel aspirates were cultured in patients with suspected SIBO, defined as ≥10 colony-forming units/mL coliform or ≥10 colony-forming units/mL UAT bacteria. History was reviewed for risk factors and potential SIBO complications. Symptoms, quality of life, psychological traits, and laboratory values were assessed. We compared groups by 2-sample t test, Wilcoxon rank sum test, and the Fisher exact test. Overall associations of primary and secondary endpoints with type of bacterial overgrowth were assessed by analysis of variance F-test, Kruskal-Wallis test, and the Fisher exact tests. Associations of risk factors with type of overgrowth were explored using multinomial logistic regression. Results: Among 76 patients, 37 had SIBO (68% coliform, 33% UAT) and 39 did not. Conditions (P=0.02) and surgery (P<0.01) associated with decreased gastric acid were associated with SIBO. In multinomial logistic regression, conditions of decreased acid was associated with UAT SIBO [odds ratio (OR), 5.8; 95% confidence interval, 1.4-33.3]. Surgery causing decreased acid was associated with UAT [OR, 9.5 (1.4-106)] and coliform SIBO [OR, 8.4 (1.6-86.4)]. Three patients with discontinuous small bowel had coliform SIBO [OR, 17.4 (1.2-2515)]. There were no differences in complications, overall symptoms, quality of life, or psychological traits. Conclusions: Conditions or surgeries associated with decreased gastric acid are associated with SIBO diagnosis by culture

Evaluation of timed barium esophagram after per-oral endoscopic myotomy to predict clinical response

Background and study aims: The aim of this study was to evaluate whether timed barium esophagram within 24 hours post-per-oral endoscopic myotomy (POEM) (TBE-PP) could predict clinical outcomes. Patients and methods: This was a single-center retrospective study of prospectively collected data on consecutive patients with ≥ 6-month follow-up who underwent POEM followed by TBE-PP. Esophageal contrast retention 2 minutes after TBE-PP was assessed as Grade 1 ( 90 %). Eckardt score, esophagogastroduodenoscopy (EGD), high-resolution manometry (HRM) and function lumen imaging probe (FLIP) of the esophagogastric junction (EGJ) were obtained at baseline. These tests along with pH testing of antisecretory therapy were repeated 6 and 24 months after POEM. Clinical response by Eckardt score ≤ 3, EGJ-distensibility index (EGJ-DI) > 2.8 mm 2 /mm Hg, and integrated relaxation pressure (IRP) < 15 mm Hg and incidence of gastroesophageal reflux disease (GERD) were compared by transit time. Results: Of 181 patients (58 % male, mean 53 ± 17 yr), TBE-PP was classified as Grade 1 in 122 (67.4 %), Grade 2 in 41 (22.7 %), Grade 3 in 14 (7.7 %) and Grade 4 in 4 (2.2 %). At 6 months, overall clinical response by ES (91.7 %), IRP (86.6 %), EGJ-DI (95.7 %) and the diagnosis of GERD (68.6 %) was similar between Grade 1 and Grade 2-4 TBE-PP. At 24 months, Grade 1 had a higher frequency of a normal IRP compared to Grades 2-4 (95.7 % vs. 60 %, P = 0.021) but overall response by ES (91.2 %), EGJ-DI (92.3 %) and the diagnosis of GERD (74.3 %) were similar. Conclusions: Contrast emptying rate by esophagram after POEM has limited utility to predict clinical response or risk of post-procedure GERD

Philosophy of religion as hermeneutics of contemplation according to Dewi Z. Phillips

Dewi Z. Phillips maintains that philosophy must have a contemplative character. Applied to religion, it takes the form of a hermeneutics of contemplation that emphasizes the role concepts play in human life. While some philosophers try to bring philosophy to bear on to religion, others try to bring religion to bear on to philosophy; seeing their task as being for or against religion. According to Phillips, both these views are confused. Instead, the philosophy of religion must strive to understand religion on its own terms: showing that a sensibility should be possible that does justice to both belief and atheism. In order to appreciate Phillips' philosophy of religion, it is essential to recognize the three authors that have contributed to his thinking: Ludwig Wittgenstein, Soren Kierkegaard, and Simone Weil. From Wittgenstein, Phillips learns the philosophical method, Kierkegaard teaches Phillips what it means to be a religious author, and Simone Weil imparts Phillips with an authentic sense of religious belief and understanding. Throughout his career Phillips has been poorly understood because he refuses to be pinned down to the categories and frameworks within which philosophers of religion and theologians traditionally define themselves. For Phillips, a contemplative conception of the philosophy of religion endeavours to show just how far philosophy can bring one in a religious dimension: trying to enable a person to be conceptually clear about the matters at hand and to realize when a personal judgment must be made

Symptom association for gastroesophageal reflux disease by PH monitoring after peroral endoscopic myotomy: GERD and symptoms after POEM

Introduction: There are limited data correlating symptoms with reflux episodes during pH studies after POEM. Methods: Consecutive patients who underwent POEM followed ≥6 months later by 48-hour ambulatory wireless pH testing off antisecretory therapy were identified. Reflux symptom association (RSA) was defined as SAP >95%. Results: The most frequent of symptoms of heartburn (47.2%), cough (45.1%) and chest pain (39.6%) were associated with a positive RSA (SAP >95%) in 20.9%, 17.1% and 19.4%, respectively. Discussion: There is poor correlation between reported symptoms and esophageal acid exposure during pH testing after POEM