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

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.

Download Full-text

W1699 Toll-Like Receptor mRNA Expression Is Selectively Increased in the Colonic Mucosa of Two Animal Models of Chronic Stress: Relevance to Irritable Bowel Syndrome

Gastroenterology ◽

10.1016/s0016-5085(09)63322-9 ◽

2009 ◽

Vol 136 (5) ◽

pp. A-720

Author(s):

Declan P. McKernan ◽

Aoife Nolan ◽

Siobhain M. O'Mahony ◽

Niall P. Hyland ◽

Elizabeth Brint ◽

...

Keyword(s):

Irritable Bowel Syndrome ◽

Animal Models ◽

Mrna Expression ◽

Chronic Stress ◽

Colonic Mucosa ◽

Toll Like Receptor ◽

Receptor Mrna ◽

Irritable Bowel

Download Full-text

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00080.2015 ◽

2015 ◽

Vol 309 (1) ◽

pp. G10-G20 ◽

Cited By ~ 24

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.

Download Full-text