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.

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.

Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers

2006 ◽  
Vol 290 (5) ◽  
pp. G942-G947 ◽  
Author(s):  
Michael Camilleri ◽  
Adil E. Bharucha ◽  
Ryuji Ueno ◽  
Duane Burton ◽  
George M. Thomforde ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Chloride Channel ◽  
Chloride Channels ◽  
Gastrointestinal Transit ◽  
Intestinal Secretion ◽  
Gastric Volume ◽  
Colonic Transit ◽  
Controlled Study ◽  
Double Blind

Chloride channels modulate gastrointestinal neuromuscular functions in vitro. Lubiprostone, a selective type 2 chloride channel (ClC-2) activator, induces intestinal secretion and has been shown to relieve constipation in clinical trials; however, the effects of lubiprostone on gastric function and whole gut transit in humans are unclear. Our aim was to compare the effects of the selective ClC-2 activator lubiprostone on maximum tolerated volume (MTV) of a meal, postprandial symptoms, gastric volumes, and gastrointestinal and colonic transit in humans. We performed a randomized, parallel-group, double-blind, placebo-controlled study evaluating the effects of lubiprostone (24 μg bid) in 30 healthy volunteers. Validated methods were used: scintigraphic gastrointestinal and colonic transit, SPECT to measure gastric volumes, and the nutrient drink (“satiation”) test to measure MTV and postprandial symptoms. Lubiprostone accelerated small bowel and colonic transit, increased fasting gastric volume, and retarded gastric emptying. MTV values were reduced compared with placebo; however, the MTV was within the normal range for healthy adults in 13 of 14 participants, and there was no significant change compared with baseline measurements. Lubiprostone had no significant effect on postprandial gastric volume or aggregate symptoms but did decrease fullness 30 min after the fully satiating meal. Thus the ClC-2 activator lubiprostone accelerates small intestinal and colonic transit, which confers potential in the treatment of constipation.

scholarly journals Atorvastatin Modulates Bile Acid Homeostasis in Mice with Diet-Induced Nonalcoholic Steatohepatitis

2021 ◽  
Vol 22 (12) ◽  
pp. 6468
Author(s):  
Hana Lastuvkova ◽  
Fatemeh Alaei Faradonbeh ◽  
Jolana Schreiberova ◽  
Milos Hroch ◽  
Jaroslav Mokry ◽  
...  
Keyword(s):  
Bile Acid ◽  
Nonalcoholic Steatohepatitis ◽  
Plasma Concentrations ◽  
Liver Steatosis ◽  
Saturated Fat ◽  
Cardiovascular Complications ◽  
Biliary Secretion ◽  
Fecal Excretion ◽  
High Cholesterol Diet ◽  
Chow Diet

Bile acids (BA) play a significant role in the pathophysiology of nonalcoholic steatohepatitis (NASH). The present study evaluates the modulation of bile acid metabolomics by atorvastatin, a cholesterol-lowering agent commonly used to treat cardiovascular complications accompanying NASH. NASH was induced in mice by 24 weeks of consuming a high–saturated fat, high-fructose, and high-cholesterol diet (F), with atorvastatin administered orally (20 mg/kg/day) during the last three weeks. Biochemical and histological analyses confirmed the effectiveness of the F diet in inducing NASH. Untreated NASH animals had significantly reduced biliary secretion of BA and increased fecal excretion of BA via decreased apical sodium-dependent bile salt transporter (Asbt)-mediated reabsorption. Atorvastatin decreased liver steatosis and inflammation in NASH animals consistently with a reduction in crucial lipogenic enzyme stearoyl–coenzyme A (CoA) desaturase-1 and nuclear factor kappa light chain enhancer of activated B-cell pro-inflammatory signaling, respectively. In this group, atorvastatin also uniformly enhanced plasma concentration, biliary secretion and fecal excretion of the secondary BA, deoxycholic acid (DCA). However, in the chow diet–fed animals, atorvastatin decreased plasma concentrations of BA, and reduced BA biliary secretions. These changes stemmed primarily from the increased fecal excretion of BA resulting from the reduced Asbt-mediated BA reabsorption in the ileum and suppression of synthesis in the liver. In conclusion, our results reveal that atorvastatin significantly modulates BA metabolomics by altering their intestinal processing and liver synthesis in control and NASH mice.

Cold-restraint stress increases rat fecal pellet output and colonic transit

1990 ◽  
Vol 258 (3) ◽  
pp. G329-G337 ◽  
Author(s):  
F. C. Barone ◽  
J. F. Deegan ◽  
W. J. Price ◽  
P. J. Fowler ◽  
J. D. Fondacaro ◽  
...  
Keyword(s):  
Restraint Stress ◽  
Fecal Pellet ◽  
Gastrointestinal Transit ◽  
Colonic Transit ◽  
Gastric Ulcers ◽  
Small Intestinal Transit ◽  
Fluid Content ◽  
Fecal Output ◽  
Cold Restraint Stress ◽  
Cold Restraint

Increased fecal pellet output that occurs during cold-restraint stress (CRS) was evaluated systematically. Free-feeding rats, which exhibit a reduced occurrence of gastric ulcers under these conditions, were studied. CRS significantly increased fecal pellet production and fluid content. However, the fecal output produced during CRS was not associated with increased gut secretory activity or somatic motor activity associated with cold restraint and did not occur in anesthetized animals. Cold and restraint stress were additive in producing increased fecal output. Significant dose-related decreases in fecal output were produced by drugs that decrease gut transit (i.e., B-HT 920, clonidine, Lomotil, loperamide, and lidamidine). Anticholinergic-antisecretory drugs, antidepressants, and tranquilizers had little effect on fecal output or fluid content. Changes in gastrointestinal transit did not contribute to the increased fecal output during CRS. Transit in the lower small intestine was not altered, but the cecum tended to empty more contents into the large intestine during CRS. Colonic transit was dramatically affected by CRS, which eliminated retrograde transit and produced the evacuation of the majority of colonic contents. The increased colonic transit produced by CRS was decreased in a dose-related fashion by hexamethonium, nifedipine, loperamide, and B-HT 920. In several time-response and drug-inhibition studies during CRS, both fecal pellet output and colonic transit were affected similarly. These data indicate that CRS appears to change central nervous system output to the colon and that it alters colonic smooth muscle motility in a manner that facilitates colonic transit and evacuation. Small intestinal transit is not involved in this phenomenon and is regulated differently during CRS.

Time course of fecal steroid-C14 excretion in various rodents

1963 ◽  
Vol 205 (6) ◽  
pp. 1159-1162 ◽  
Author(s):  
W. T. Beher ◽  
G. D. Baker ◽  
D. G. Penney
Keyword(s):  
Bile Acid ◽  
Guinea Pig ◽  
Time Course ◽  
Mevalonic Acid ◽  
Fecal Excretion ◽  
Rat Tissues ◽  
Neutral Sterol ◽  
Excretion Rates ◽  
Intermediate Rate ◽  
Intermediate Amount

A study was made of the rates of fecal excretion of sterol-C14 and bile acid-C14 during a 7-day period after an intraperitoneal injection of dl-mevalonic acid-2-C14. The percentages of fecal C14 steroids excreted as bile acid-C14 by several species were: mouse, 51%; hamster, 62%; rat, 62%; guinea pig, 33%; gerbil, 66%; and rabbit, 56%. The balance of excretion was neutral sterol-C14. The ratios of fecal bile acid-C14 to neutral sterol-C14 varied with time. The animals can be divided into three groups in respect to rate of excretion: rat and mouse had high excretion rates; gerbil an intermediate rate; while hamster, guinea pig, and rabbit had low rates. The amounts of C14 sterols retained in serum, liver, and carcass after 7 days were determined. The highest retained activity was in guinea pig and rabbit, the lowest in rat tissues. The sum of excreted steroid-C14 and retained sterol-C14, which equals total synthesized steroid-C14, was calculated. Guinea pig, rat, and mouse incorporated the greatest amount of C14; gerbil, an intermediate amount; and hamster, the smallest amount.

scholarly journals Evidence for the Existence of a Soybean Resistant Protein That Captures Bile Acid and Stimulates Its Fecal Excretion

2006 ◽  
Vol 70 (12) ◽  
pp. 2844-2852 ◽  
Author(s):  
Noriko HIGAKI ◽  
Kenji SATO ◽  
Hitoshi SUDA ◽  
Tomohiko SUZUKA ◽  
Takeo KOMORI ◽  
...  
Keyword(s):  
Bile Acid ◽  
Fecal Excretion

scholarly journals Sa1947 – Randomized, Double-Blind, Placebo-Controlled Trial of Colesevelam in Patients with Bile Acid Diarrhea: Effects on Fecal Bile Acids, Colonic Transit, and Bowel Functions

2019 ◽  
Vol 156 (6) ◽  
pp. S-464-S-465 ◽  
Author(s):  
Priya Vijayvargiya ◽  
Leslie J. Donato ◽  
Lawrence A. Szarka ◽  
Andres Acosta ◽  
Alan J. Lueke ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Controlled Trial ◽  
Colonic Transit ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Fecal Bile Acids
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