scholarly journals Sigmoid colon mucosal gene expression supports alterations of neuronal signaling in irritable bowel syndrome with constipation

2018 ◽  
Vol 315 (1) ◽  
pp. G140-G157 ◽  
Author(s):  
Elizabeth J. Videlock ◽  
Swapna Mahurkar-Joshi ◽  
Jill M. Hoffman ◽  
Dimitrios Iliopoulos ◽  
Charalabos Pothoulakis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Irritable Bowel Syndrome ◽  
Sigmoid Colon ◽  
Microarray Analysis ◽  
Gene Networks ◽  
Expression Profiles ◽  
Gene Set Enrichment Analysis ◽  
Healthy Controls ◽  
Neuronal Signaling ◽  
Irritable Bowel

Peripheral factors likely play a role in at least a subset of irritable bowel syndrome (IBS) patients. Few studies have investigated mucosal gene expression using an unbiased approach. Here, we performed mucosal gene profiling in a sex-balanced sample to identify relevant signaling pathways and gene networks and compare with publicly available profiling data from additional cohorts. Twenty Rome III+ IBS patients [10 IBS with constipation (IBS-C), 10 IBS with diarrhea (IBS-D), 5 men/women each), and 10 age-/sex-matched healthy controls (HCs)] underwent sigmoidoscopy with biopsy for gene microarray analysis, including differential expression, weighted gene coexpression network analysis (WGCNA), gene set enrichment analysis, and comparison with publicly available data. Expression levels of 67 genes were validated in an expanded cohort, including the above samples and 18 additional participants (6 each of IBS-C, IBS-D, HCs) using NanoString nCounter technology. There were 1,270 differentially expressed genes (FDR < 0.05) in IBS-C vs. HCs but none in IBS or IBS-D vs. HCs. WGNCA analysis identified activation of the cAMP/protein kinase A signaling pathway. Nine of 67 genes were validated by the NanoString nCounter technology (FDR < 0.05) in the expanded sample. Comparison with publicly available microarray data from the Mayo Clinic and University of Nottingham supports the reproducibility of 17 genes from the microarray analysis and three of nine genes validated by nCounter in IBS-C vs. HCs. This study supports the involvement of peripheral mechanisms in IBS-C, particularly pathways mediating neuronal signaling. NEW & NOTEWORTHY Peripheral factors play a role in the pathophysiology of irritable bowel syndrome (IBS), which, to date, has been mostly evident in IBS with diarrhea. Here, we show that sigmoid colon mucosal gene expression profiles differentiate IBS with constipation from healthy controls. These profiling data and analysis of additional cohorts also support the concept that peripheral neuronal pathways contribute to IBS pathophysiology.

scholarly journals The Expression of Human Placental Genes Related to Carotenoid/retinoid Metabolism and Pathways (P02-005-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Xiaoming Gong ◽  
Lewis Rubin
Keyword(s):  
Gene Expression ◽  
Microarray Analysis ◽  
Fetal Development ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Retinoid Metabolism ◽  
Expression Of Genes ◽  
Β Carotene

Abstract Objectives Carotenoid/retinoids status and metabolism are essential for normal placental and fetal development. Both deficiencies and excess of retinoids and some carotenoids are associated with adverse pregnancy outcomes, such as preeclampsia and preterm birth. A group of important genes involved in regulating carotenoid/retinoid metabolism and maternal to fetal transfer in human placenta. The objective of this study is to analyze (a) the expression of genes critical for regulating carotenoid/retinoid metabolism and maternal-fetal transport in human trophoblasts and (b) placental transcriptional profiles of these pathways in response to carotenoid exposure. Methods Human cytotrophoblasts (CTBs) were isolated from term placentas. CTB RNA was used to analyze the expression of genes involved in carotenoid/retinoid metabolism and pathways by qRT-PCT. First trimester-like trophoblasts (HTR-8/SVneo) were treated with either β-carotene or lycopene. RNAs were isolated and gene expression were analyzed by DNA microarrays. Results Human CTBs express retinoid metabolism and pathways-related genes, including Stra6, Lrat, Rdh5, Rdh10, Aldh1a1, Aldh1a2, Aldh1a3, Aldh8a1, Cyp26a1, and Cyp26b1, but not carotenoid metabolism genes, BCO1 and BCO2. Microarray analysis of placental gene expression profile revealed a total of 872 and 756 differentially expressed genes, respectively, compared to the control. Gene set enrichment analysis and functional annotation clustering was performed to characterize the genes differentially expressed in either β-carotene or lycopene-treated HTR-8/SVneo cells. Many known retinoid metabolism related genes and genes involved in regulation of retinoid signaling were found, and the expression profiles of these genes were markedly different in response to β-carotene treatments. Finally, the qRT-PCR and microarray analysis results showed similar gene expression patterns of carotenoid/retinoid metabolism and pathways. Conclusions These findings suggest that placental expression of genes involved in retinoid metabolism and transport in trophoblasts is critical for regulating retinoid homeostasis during placental and fetal development. Carotenoid exposure in early placental development, significantly modify the placenta gene expression related to retinoid pathways and maternal to fetal transfer. Funding Sources NIH HD421174.

Effect of sex on perception of rectosigmoid stimuli in irritable bowel syndrome

2006 ◽  
Vol 291 (2) ◽  
pp. R277-R284 ◽  
Author(s):  
Lin Chang ◽  
Emeran A. Mayer ◽  
Jennifer S. Labus ◽  
Max Schmulson ◽  
Oh Young Lee ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Sigmoid Colon ◽  
Healthy Controls ◽  
Perceptual Sensitivity ◽  
Control Groups ◽  
Healthy Men ◽  
Before And After ◽  
Irritable Bowel ◽  
And Control ◽  
The Relationship

In irritable bowel syndrome (IBS) patients, the relationship between sex and sensitivity to visceral stimuli is incompletely understood. Our aim was to evaluate the effect of sex on perceptual responses to visceral stimulation in IBS. Fifty-eight IBS patients (mean age 42 ± 1 yr; 34 men, 24 women) and 26 healthy controls (mean age 38 ± 3 yr; 9 men, 17 women) underwent barostat-assisted distensions of the rectum and sigmoid colon. Rectal discomfort thresholds were measured using a randomized, phasic distension paradigm before and after repeated noxious sigmoid stimulation (SIG, 60-mmHg pulses). Sex had a significant effect on rectal discomfort thresholds. Women with IBS were the most sensitive (lower thresholds [27 ± 2.7 mmHg] and higher ratings), with significantly lower rectal discomfort thresholds compared with men with IBS (38 ± 2.3 mmHg) and healthy women who were the least sensitive (41.9 ± 3.2 mmHg; both P < 0.01). There were no significant differences in rectal discomfort thresholds between healthy men (34 ± 4.3 mmHg) and men with IBS. Across both IBS and control groups, women demonstrated a significant lowering of discomfort thresholds after noxious sigmoid stimulation ( P < 0.01), while men did not. Sex significantly influences perceptual sensitivity to rectosigmoid distension. Women show greater perceptual responses to this paradigm.

scholarly journals Evidence of altered mucosa-associated and fecal microbiota composition in patients with Irritable Bowel Syndrome

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Johanna Sundin ◽  
Imran Aziz ◽  
Sofia Nordlander ◽  
Annikka Polster ◽  
Yue O. O. Hu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Irritable Bowel Syndrome ◽  
Sigmoid Colon ◽  
Bacterial Overgrowth ◽  
Amplicon Sequencing ◽  
Small Intestinal Bacterial Overgrowth ◽  
Breath Tests ◽  
Bacterial Composition ◽  
Small Intestinal ◽  
Irritable Bowel

AbstractAltered bacterial composition and small intestinal bacterial overgrowth (SIBO) may be associated with irritable bowel syndrome (IBS). This study aimed to determine the fecal and mucosa-associated bacterial composition along the gastrointestinal (GI) tract and to assess SIBO in IBS. Bacterial composition of feces, and mucosa of the duodenum and sigmoid colon was determined by 16S rRNA-amplicon-sequencing. SIBO was evaluated by bacterial culture of duodenal aspirate, glucose and lactulose breath tests. Mucosal antibacterial gene expression was assessed by PCR Array. The bacterial profiles of feces and the mucosa of sigmoid colon, but not duodenum, differed between IBS patients (n = 17) and HS (n = 20). The IBS specific bacterial profiles were linked to the colonic antibacterial gene expression. Fecal bacterial profile differed between IBS subtypes, while the mucosa-associated bacterial profile was associated with IBS symptom severity and breath tests results at baseline (H2 and/or CH4 ≥ 15 ppm). The prevalence of SIBO was similar between IBS patients and HS. This study demonstrates that alterations in the bacterial composition of the sigmoid colon of IBS patients were linked to symptoms and immune activation. While breath tests reflected the mucosa-associated bacterial composition, there was no evidence for high prevalence of SIBO or small intestinal bacterial alterations in IBS.

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.

Utilizing Cancer - Functional Gene Set - Compound Networks to Identify Putative Drugs for Breast Cancer

2018 ◽  
Vol 21 (2) ◽  
pp. 74-83
Author(s):  
Tzu-Hung Hsiao ◽  
Yu-Chiao Chiu ◽  
Yu-Heng Chen ◽  
Yu-Ching Hsu ◽  
Hung-I Harry Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Therapy ◽  
Cancer Treatment ◽  
Cancer Survival ◽  
Expression Profiles ◽  
Functional Gene ◽  
Gene Set Enrichment Analysis ◽  
Gene Set ◽  
Gene Sets

Aim and Objective: The number of anticancer drugs available currently is limited, and some of them have low treatment response rates. Moreover, developing a new drug for cancer therapy is labor intensive and sometimes cost prohibitive. Therefore, “repositioning” of known cancer treatment compounds can speed up the development time and potentially increase the response rate of cancer therapy. This study proposes a systems biology method for identifying new compound candidates for cancer treatment in two separate procedures. Materials and Methods: First, a “gene set–compound” network was constructed by conducting gene set enrichment analysis on the expression profile of responses to a compound. Second, survival analyses were applied to gene expression profiles derived from four breast cancer patient cohorts to identify gene sets that are associated with cancer survival. A “cancer–functional gene set– compound” network was constructed, and candidate anticancer compounds were identified. Through the use of breast cancer as an example, 162 breast cancer survival-associated gene sets and 172 putative compounds were obtained. Results: We demonstrated how to utilize the clinical relevance of previous studies through gene sets and then connect it to candidate compounds by using gene expression data from the Connectivity Map. Specifically, we chose a gene set derived from a stem cell study to demonstrate its association with breast cancer prognosis and discussed six new compounds that can increase the expression of the gene set after the treatment. Conclusion: Our method can effectively identify compounds with a potential to be “repositioned” for cancer treatment according to their active mechanisms and their association with patients’ survival time.

scholarly journals Identification of potential biomarkers for abdominal pain in IBS patients by bioinformatics approach

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhongyuan Lin ◽  
Yimin Wang ◽  
Shiqing Lin ◽  
Decheng Liu ◽  
Guohui Mo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Irritable Bowel Syndrome ◽  
Abdominal Pain ◽  
Gastrointestinal Disease ◽  
Rectal Mucosa ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Irritable Bowel ◽  
Potential Biomarkers

Abstract Background Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disease characterized by chronic abdominal discomfort and pain. The mechanisms of abdominal pain, as a relevant symptom, in IBS are still unclear. We aimed to explore the key genes and neurobiological changes specially involved in abdominal pain in IBS. Methods Gene expression data (GSE36701) was downloaded from Gene Expression Omnibus database. Fifty-three rectal mucosa samples from 27 irritable bowel syndrome with diarrhea (IBS-D) patients and 40 samples from 21 healthy volunteers as controls were included. Differentially expressed genes (DEGs) between two groups were identified using the GEO2R online tool. Functional enrichment analysis of DEGs was performed on the DAVID database. Then a protein–protein interaction network was constructed and visualized using STRING database and Cytoscape. Results The microarray analysis demonstrated a subset of genes (CCKBR, CCL13, ACPP, BDKRB2, GRPR, SLC1A2, NPFF, P2RX4, TRPA1, CCKBR, TLX2, MRGPRX3, PAX2, CXCR1) specially involved in pain transmission. Among these genes, we identified GRPR, NPFF and TRPA1 genes as potential biomarkers for irritating abdominal pain of IBS patients. Conclusions Overexpression of certain pain-related genes (GRPR, NPFF and TRPA1) may contribute to chronic visceral hypersensitivity, therefore be partly responsible for recurrent abdominal pain or discomfort in IBS patients. Several synapses modification and biological process of psychological distress may be risk factors of IBS.

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.

Sign in / Sign up

Export Citation Format

Share Document