scholarly journals Association of HLA-DQ gene with bowel transit, barrier function, and inflammation in irritable bowel syndrome with diarrhea

2012 ◽  
Vol 303 (11) ◽  
pp. G1262-G1269 ◽  
Author(s):  
Maria I. Vazquez-Roque ◽  
Michael Camilleri ◽  
Thomas Smyrk ◽  
Joseph A. Murray ◽  
Jessica O'Neill ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Protein Expression ◽  
Mrna Expression ◽  
Barrier Function ◽  
Intraepithelial Lymphocytes ◽  
Colonic Transit ◽  
Mucosal Inflammation ◽  
Hla Dq ◽  
Irritable Bowel ◽  
Hla Dq2

Patients with irritable bowel syndrome (IBS) with diarrhea (IBS-D) carrying human leukocyte antigen (HLA)-DQ2/8 genotypes benefit from gluten withdrawal. Our objective was to compare gastrointestinal barrier function, mucosal inflammation, and transit in nonceliac IBS-D patients and assess association with HLA-DQ2/8 status. In 45 IBS-D patients who were naive to prior exclusion of dietary gluten, we measured small bowel (SB) and colonic mucosal permeability by cumulative urinary lactulose and mannitol excretion (0–2 h for SB and 8–24 h for colon), inflammation on duodenal and rectosigmoid mucosal biopsies (obtained in 28 of 45 patients), tight junction (TJ) protein mRNA and protein expression in SB and rectosigmoid mucosa, and gastrointestinal and colonic transit by validated scintigraphy. SB mucosal biopsies were stained with hematoxylin-eosin to assess villi and intraepithelial lymphocytes, and immunohistochemistry was used to assess CD3, CD8, tryptase, and zonula occludens 1 (ZO-1); colonic biopsy intraepithelial lymphocytes were quantitated. Associations of HLA-DQ were assessed using Wilcoxon's rank-sum test. Relative to healthy control data, we observed a significant increase in SB permeability ( P < 0.001), a borderline increase in colonic permeability ( P = 0.10), and a decrease in TJ mRNA expression in rectosigmoid mucosa in IBS-D. In HLA-DQ2/8-positive patients, ZO-1 protein expression in the rectosigmoid mucosa was reduced compared with that in HLA-DQ2/8-negative patients and colonic transit was slower than in HLA-DQ2/8-negative patients. No other associations with HLA genotype were identified. There is abnormal barrier function (increased SB permeability and reduced mRNA expression of TJ proteins) in IBS-D relative to health that may be, in part, related to immunogenotype, given reduced ZO-1 protein expression in rectosigmoid mucosa in HLA-DQ2/8-positive relative to HLA-DQ2/8-negative patients.

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.

scholarly journals Tu1425 Relationship of HLA-DQ Genotype With Small Bowel and Colonic Transit and Permeability, and Small Bowel Inflammation in Patients With Irritable Bowel Syndrome With Diarrhea (IBS-D)

2012 ◽  
Vol 142 (5) ◽  
pp. S-829
Author(s):  
Maria I. Vazquez-Roque ◽  
Michael Camilleri ◽  
Thomas C. Smyrk ◽  
Joseph A. Murray ◽  
Jessica O'Neill ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Small Bowel ◽  
Colonic Transit ◽  
Hla Dq ◽  
Irritable Bowel ◽  
Relationship Of

scholarly journals Somatization in patients with predominant diarrhoea irritable bowel syndrome: the role of the intestinal barrier function and integrity

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Laura Prospero ◽  
Giuseppe Riezzo ◽  
Michele Linsalata ◽  
Antonella Orlando ◽  
Benedetta D’Attoma ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Barrier Function ◽  
Rating Scale ◽  
Psychological Symptoms ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Fatty Acid Binding ◽  
Gastrointestinal Symptom Rating Scale ◽  
Gi Symptoms ◽  
Irritable Bowel

Abstract Background Irritable bowel syndrome (IBS) is characterised by gastrointestinal (GI) and psychological symptoms (e.g., depression, anxiety, and somatization). Depression and anxiety, but not somatization, have already been associated with altered intestinal barrier function, increased LPS, and dysbiosis. The study aimed to investigate the possible link between somatization and intestinal barrier in IBS with diarrhoea (IBS-D) patients. Methods Forty-seven IBS-D patients were classified as having low somatization (LS = 19) or high somatization (HS = 28) according to the Symptom Checklist-90-Revised (SCL-90-R), (cut-off score = 63). The IBS Severity Scoring System (IBS-SSS) and the Gastrointestinal Symptom Rating Scale (GSRS) questionnaires were administered to evaluate GI symptoms. The intestinal barrier function was studied by the lactulose/mannitol absorption test, faecal and serum zonulin, serum intestinal fatty-acid binding protein, and diamine oxidase. Inflammation was assessed by assaying serum Interleukins (IL-6, IL-8, IL-10), and tumour necrosis factor-α. Dysbiosis was assessed by the urinary concentrations of indole and skatole and serum lipopolysaccharide (LPS). All data were analysed using a non-parametric test. Results The GI symptoms profiles were significantly more severe, both as a single symptom and as clusters of IBS-SSS and GSRS, in HS than LS patients. This finding was associated with impaired small intestinal permeability and increased faecal zonulin levels. Besides, HS patients showed significantly higher IL-8 and lowered IL-10 concentrations than LS patients. Lastly, circulating LPS levels and the urinary concentrations of indole were higher in HS than LS ones, suggesting a more pronounced imbalance of the small intestine in the former patients. Conclusions IBS is a multifactorial disorder needing complete clinical, psychological, and biochemical evaluations. Trial registration: https://clinicaltrials.gov/ct2/show/NCT03423069.

scholarly journals Intestinal barrier dysfunction in irritable bowel syndrome: a systematic review

2021 ◽  
Vol 14 ◽  
pp. 175628482199358
Author(s):  
Nikita Hanning ◽  
Adam L. Edwinson ◽  
Hannah Ceuleers ◽  
Stephanie A. Peters ◽  
Joris G. De Man ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Systematic Review ◽  
Irritable Bowel Syndrome ◽  
Abdominal Pain ◽  
Barrier Function ◽  
Significant Proportion ◽  
Healthy Controls ◽  
Barrier Dysfunction ◽  
Irritable Bowel

Background and Aim: Irritable bowel syndrome (IBS) is a complex and heterogeneous disorder. Sensory, motor and barrier dysfunctions are the key physiological endophenotypes of IBS. Our aim is to review studies evaluating barrier dysfunction in adults and children with IBS, as well as to link those changes with IBS symptomatology and quality of life. Methods: A comprehensive and systematic review of multiple databases was performed up to March 2020 to identify studies comparing intestinal permeability in IBS patients with healthy controls. Both in vivo and in vitro studies were considered. Results: We identified 66 studies, of which 27 used intestinal probes to quantify barrier function. The prevalence of barrier dysfunction differed between PI-IBS (17–50%), IBS-D (37–62%) and IBS-C (4–25%). At a group level, permeability was increased compared with healthy controls in IBS-D (9/13 studies) and PI-IBS (4/4 studies), but only a minority of IBS-C (2/7 studies) and not in the only IBS-M study. All four studies in children with IBS demonstrated loss of barrier function. A heterogeneous set of tight junction genes were found to be altered in small and large intestines of adults with IBS, but these have not been evaluated in children. Positive associations were identified between barrier dysfunction and bowel disturbances (6/9 studies), abdominal pain (9/13 studies), overall symptom severity (1/6 studies), depression and anxiety (1/1 study) and quality of life (1/4 studies). Fecal slurry or supernatants of IBS patients were found to induce barrier disruption in animal models (5/6 studies). Conclusions: Barrier dysfunction is present in a significant proportion of adult and all pediatric IBS studies, especially in the IBS-D and PI-IBS subtype. The majority of studies indicated a positive association between loss of barrier function and symptoms such as abdominal pain and changes in the bowel function.

Genetic Susceptibility to Inflammation is Associated With Colonic Transit and Other Intermediate Phenotypes in Irritable Bowel Syndrome

2011 ◽  
Vol 140 (5) ◽  
pp. S-152 ◽  
Author(s):  
Michael Camilleri ◽  
Paula Carlson ◽  
Sanna McKinzie ◽  
Marco Zucchelli ◽  
Mauro D'Amato ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Genetic Susceptibility ◽  
Colonic Transit ◽  
Intermediate Phenotypes ◽  
Irritable Bowel

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.

Mo1574 DIFFERENTIAL MRNA EXPRESSION IN ILEAL MUCOSAL BIOPSIES OF PATIENTS WITH IRRITABLE BOWEL SYNDROME

2020 ◽  
Vol 158 (6) ◽  
pp. S-901
Author(s):  
Xiao Jing Wang ◽  
Paula Carlson ◽  
Victor G. Chedid ◽  
Daniel B. Maselli ◽  
Ann Taylor ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Mrna Expression ◽  
Irritable Bowel ◽  
Differential Mrna Expression

scholarly journals Treatment of postinfectious irritable bowel syndrome and noninfective irritable bowel syndrome with mesalazine

2011 ◽  
Vol 48 (1) ◽  
pp. 36-40 ◽  
Author(s):  
Mauro Bafutto ◽  
José Roberto de Almeida ◽  
Nayle Vilela Leite ◽  
Enio Chaves Oliveira ◽  
Salustiano Gabriel-Neto ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Abdominal Pain ◽  
Symptom Score ◽  
Stool Frequency ◽  
Total Symptom Score ◽  
Stool Consistency ◽  
Mucosal Inflammation ◽  
Irritable Bowel Syndrome Group ◽  
Irritable Bowel ◽  
Postinfectious Irritable Bowel Syndrome

CONTEXT: Recent studies support the hypothesis that postinfectious irritable bowel syndrome and some irritable bowel syndrome patients display persistent signs of minor mucosal inflammation. Mesalazine has intestinal anti-inflammatory properties including cyclooxygenase and prostaglandin inhibition. The effects of mesalazine on postinfectious irritable bowel syndrome and noninfective irritable bowel syndrome patients are still unknown. OBJECTIVE: To observe the effects of mesalazine on postinfectious irritable bowel syndrome and noninfective irritable bowel syndrome with diarrhea patients. METHODS: Based on Rome III criteria, 61 irritable bowel syndrome with diarrhea patients (18 years old or more) were included in the evaluation. Patients were divided into two groups: postinfectious irritable bowel syndrome group, with 18 patients medicated with mesalazine 800 mg 3 times a day for 30 days; noninfective irritable bowel syndrome group, with 43 patients medicated with mesalazine 800 mg 3 times a day for 30 days. Symptom evaluations at baseline and after treatment were performed by means of a four-point Likert scale including stool frequency, stool form and consistency (Bristol Stool Scale), abdominal pain and distension (maximum score: 16; minimum score: 4). RESULTS: Postinfectious irritable bowel syndrome group presented a statistically significant reduction of the total symptom score (P<0.0001). The stool frequency was significantly reduced (P<0.0001), and stool consistency, improved (P<0.0001). Abdominal pain (P<0.0001) and abdominal distension were significantly reduced (P<0.0001). Noninfective irritable bowel syndrome group presented a statistically significant reduction of total symptom score (P<0.0001). Also, the stool frequency was significantly reduced (P<0.0001) and stool consistency, improved (P<0.0001). Abdominal pain (P<0.0001) and abdominal distention were significantly reduced (P<0.0001). There was no statistical difference between postinfectious irritable bowel syndrome group and noninfective irritable bowel syndrome group on total symptom score results at 30th day of therapy with mesalazine 800 mg 3 times a day. (P = 0.13). CONCLUSION: Mesalazine reduced key symptoms of postinfectious irritable bowel syndrome and noninfective irritable bowel syndrome with diarrhea patients.

scholarly journals Stress, Inflammation and the Irritable Bowel Syndrome

1999 ◽  
Vol 13 (suppl a) ◽  
pp. 47A-49A ◽  
Author(s):  
Stephen M Collins ◽  
Giovanni Barbara ◽  
Bruce Vallance
Keyword(s):  
Irritable Bowel Syndrome ◽  
Stressful Life Events ◽  
Human Studies ◽  
Mucosal Inflammation ◽  
Enteric Infection ◽  
Smooth Muscle Function ◽  
Inflammatory Stimuli ◽  
Irritable Bowel ◽  
Prior Stress ◽  
Made In

Studies in animals have shown that inflammation of the mucosa of the gastrointestinal tract is accompanied by changes in enteric nerve and smooth muscle function, and in gut motility and sensation. In some instances, these changes persist long after resolution of the mucosal inflammation. Some of these observations have been made in human studies of irritable bowel syndrome (IBS) in patients after an enteric infection or in patients in remission from ulcerative colitis. Stress has also been implicated as a modulator of gastrointestinal inflammation in both animal and human studies. In animals, stress causes a reactivation of previous enteric inflammation and induces the attendant physiological changes. Prior stress also enhances the response to subsequent inflammatory stimuli. In humans, postinfectious IBS tends to occur in patients with psychological profiles similar to those observed in IBS patients and in whom there is a higher incidence of stressful life events just before exposure to the infection. Taken together, these observations link stress and inflammation as a putative pathogenetic mechanism in at least a subset of IBS patients.

Mo1569 IDENTIFICATION OF COLONIC MUCOSAL MICRORNAS ALTERED IN IRRITABLE BOWEL SYNDROME AND THEIR ROLES IN INTESTINAL BARRIER FUNCTION.

2020 ◽  
Vol 158 (6) ◽  
pp. S-899
Author(s):  
Swapna Mahurkar-Joshi ◽  
Carl R. Rankin ◽  
Elizabeth J. Videlock ◽  
Artin Soroosh ◽  
Abhishek Verma ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Irritable Bowel
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