scholarly journals 2103 Fecal bile acids, fecal short-chain fatty acids, and the intestinal microbiota in patients with irritable bowel syndrome (IBS) and control volunteers

2018 ◽  
Vol 2 (S1) ◽  
pp. 12-13
Author(s):  
Andrea Shin ◽  
David Nelson ◽  
John Wo ◽  
Michael Camilleri ◽  
Toyia James-Stevenson ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Bile Acid ◽  
Organic Acids ◽  
Gastrointestinal Transit ◽  
Fecal Microbiota ◽  
Colonic Transit ◽  
Short Chain ◽  
Fecal Excretion ◽  
Acid Excretion ◽  
Irritable Bowel

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.

scholarly journals 2073

2017 ◽  
Vol 1 (S1) ◽  
pp. 30-30
Author(s):  
Andrea Shin ◽  
David Nelson ◽  
John Wo ◽  
Michael Camilleri ◽  
Anita Gupta ◽  
...  
Keyword(s):  
Bile Acid ◽  
Organic Acids ◽  
Linear Models ◽  
Treatment Strategies ◽  
Gastrointestinal Transit ◽  
Intestinal Secretion ◽  
Target Population ◽  
Fecal Microbiota ◽  
Colonic Transit ◽  
Fecal Excretion

OBJECTIVES/SPECIFIC AIMS: Recent data suggest that fecal microbiota and intraluminal organic acids may play an important role in irritable bowel syndrome (IBS) pathogenesis through effects on intestinal secretion and motility. Understanding their contribution will be critical in developing diagnostic and treatment strategies. Objectives and goals of this study will be to: (1) compare fecal microbiota and fecal organic acids in 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 a prospective 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 predominant and constipation-predominant, IBS-D, and IBS-C) and asymptomatic controls. Exclusion criteria are: (a) history of microscopic colitis, inflammatory bowel disease, celiac disease, cancer, chronic infectious disease, immunodeficiency, uncontrolled thyroid disease, liver disease, or elevated AST/ALT>2.0x 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 prior to study participation, (f) prebiotic or probiotic usage within the 2 weeks prior to study initiation, (g) tobacco users. Primary outcomes will be fecal bile acid excretion and profile, short-chain fatty acid (SCFA) 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.

Effects of Bile Acid Binding on Colonic Transit in Irritable Bowel Syndrome with Diarrhea

2009 ◽  
Vol 104 ◽  
pp. S487-S488
Author(s):  
Suwebatu Odunsi ◽  
Michael Camilleri ◽  
Duane Burton ◽  
Sanna McKinzie ◽  
Irene Busciglio ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Bile Acid ◽  
Colonic Transit ◽  
Bile Acid Binding ◽  
Irritable Bowel

248 Candidate Genes, Mucosal mRNA and Protein Expression, Colon Transit and Bile Acid Excretion in Irritable Bowel Syndrome-Diarrhea

2015 ◽  
Vol 148 (4) ◽  
pp. S-56
Author(s):  
Michael Camilleri ◽  
Paula Carlson ◽  
Andres Acosta ◽  
Nelson Valentin Feliciano ◽  
Irene A. Busciglio ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Bile Acid ◽  
Protein Expression ◽  
Candidate Genes ◽  
Acid Excretion ◽  
Bile Acid Excretion ◽  
Mrna And Protein Expression ◽  
Irritable Bowel ◽  
Colon Transit

scholarly journals Fecal Bile Acids and Fecal Short Chain Fatty Acids in Patients with Irritable Bowel Syndrome and Control Volunteers

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Chirag Patel ◽  
Carolyn Lockett ◽  
Huiping Xu ◽  
Andrea Shin
Keyword(s):  
Fatty Acids ◽  
Irritable Bowel Syndrome ◽  
Organic Acids ◽  
Bile Acids ◽  
Short Chain Fatty Acids ◽  
Small Sample ◽  
Short Chain ◽  
Fecal Bile Acids ◽  
Irritable Bowel ◽  
Chain Fatty Acids

Background and Aims: Fecal bile acids (BAs), short chain fatty acids (SCFAs), and gut microbiome may be implicated in irritable bowel syndrome (IBS) pathophysiology. Our aim was to compare fecal organic acids between IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), and controls.   Methods: Stool samples were collected from 17 controls, 5 IBS-C, and 5 IBS-D volunteers during a 4-day high fat diet. Aliquots were stored for future analysis of the fecal microbiota. Fecal SCFA and BA analyses were conducted at the Metabolite Profiling Facility at Purdue University and Laboratory Medicine and Pathology at Mayo Clinic. We compared SCFA and BA levels among groups using the Wilcoxon rank sum test. Gamma and linear regression were used to compare SCFAs and BAs adjusting for age and body mass index (BMI).  Results: Fecal acetate levels (mean+SD, µg/mg) were higher in IBS-C (11.3±7) than in controls (6.1±3.3) or IBS-D (7.7±2), although not statistically significant (p=0.19). Total fecal BAs (median [IQR], %) were higher in IBS-D (675 [484-778]) than in controls (342 [130-640]) or IBS-C (321.5 (34.5-718); however, differences were not significant. No significant differences were observed in BAs or SCFAs between groups in multivariate analyses.  Conclusion: We are unable to show significant differences in organic acid levels in IBS and controls. Lack of association may be due to small sample size. Future investigation of larger patient numbers with incorporation of transit and microbiome analyses may shed further light on the role of organic acids in IBS to identify new biomarkers and treatment targets.

Tu2057 Assessment of Bowel Symptoms, Colonic Transit, and the Relationship to Fecal Bile Acid (BA) Excretion in Health and Irritable Bowel Syndrome (IBS)

2013 ◽  
Vol 144 (5) ◽  
pp. S-915 ◽  
Author(s):  
Andrea Shin ◽  
Michael Camilleri ◽  
Irene A. Busciglio ◽  
Duane D. Burton ◽  
Priya Vijayvargiya ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Bile Acid ◽  
Colonic Transit ◽  
Fecal Bile Acid ◽  
Bowel Symptoms ◽  
Irritable Bowel ◽  
The Relationship

scholarly journals Colonic mucosal gene expression and genotype in irritable bowel syndrome patients with normal or elevated fecal bile acid excretion

2015 ◽  
Vol 309 (1) ◽  
pp. G10-G20 ◽  
Author(s):  
Michael Camilleri ◽  
Paula Carlson ◽  
Andres Acosta ◽  
Irene Busciglio
Keyword(s):  
Gene Expression ◽  
Irritable Bowel Syndrome ◽  
Bile Acid ◽  
Ion Transport ◽  
Mrna Expression ◽  
Colonic Transit ◽  
Healthy Controls ◽  
False Detection ◽  
Irritable Bowel ◽  
Intestinal Ion Transport

The mucosal gene expression in rectosigmoid mucosa (RSM) in irritable bowel syndrome with diarrhea (IBS-D) is unknown. Our objectives were, first, to study mRNA expression [by RT2 PCR of 19 genes pertaining to tight junctions, immune activation, intestinal ion transport and bile acid (BA) homeostasis] in RSM in IBS-D patients ( n = 47) and healthy controls ( n = 17) and study expression of a selected protein (PDZD3) in 10 IBS-D patients and 4 healthy controls; second, to assess RSM mRNA expression according to genotype and fecal BA excretion (high ≥2,337 μmol/48 h); and third, to determine whether genotype or mucosal mRNA expression is associated with colonic transit or BA parameters. Fold changes were corrected for false detection rate for 19 genes studied ( P < 0.00263). In RSM in IBS-D patients compared with controls, mRNA expression of GUC2AB, PDZD3, and PR2Y4 was increased, whereas CLDN1 and FN1 were decreased. One immune-related gene was upregulated (C4BP4) and one downregulated (CCL20). There was increased expression of a selected ion transport protein (PDZD3) on immunohistochemistry and Western blot in IBS-D compared with controls ( P = 0.02). There were no significant differences in mucosal mRNA in 20 IBS-D patients with high compared with 27 IBS-D patients with normal BA excretion. GPBAR1 ( P < 0.05) was associated with colonic transit. We concluded that mucosal ion transport mRNA (for several genes and PDZD3 protein) is upregulated and barrier protein mRNA downregulated in IBS-D compared with healthy controls, independent of genotype. There are no differences in gene expression in IBS-D with high compared with normal fecal BA excretion.

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