RNA transcriptomics of healthy and PI-IBS colonic biopsies
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE168759 | GEO | 2021/12/31
REPOSITORIES: GEO
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Project description:Study 1: Transcriptomic profiles in colon tissue from inflammatory bowel diseases patients in relation to N-nitroso compound exposure and colorectal cancer risk Study 1: N-nitroso compounds (NOC) have been suggested to play a role in human cancer development but definitive evidence is still lacking. In this study we investigated gene expression modifications induced in human colon tissue in relation to NOC exposure to gain insight in the relevance of these compounds in human colorectal cancer (CRC) development. Since there are indications that inflammation stimulates endogenous NOC formation, the study population consisted of patients with inflammatory bowel disease (IBD) and irritable bowel syndrome patients as controls without inflammation. Strong transcriptomic differences were identified in colonic biopsies from IBD patients and compared to controls that enhance the understanding of IBD pathophysiology. However, fecal NOC levels were not increased in IBD patients, suggesting that inflammation did not stimulate NOC formation. By relating gene expression changes of all subjects to fecal NOC levels, we did, however, identify a NOC exposure-associated transcriptomic response that suggests that physiological NOC concentrations may induce genotoxic responses and chromatin modifications in human colon tissue, both of which are linked to carcinogenicity. In a network analysis, chromatin modifications were linked to 11 significantly modulated histone genes, pointing towards a possible epigenetic mechanism that may be relevant in comprehending the molecular basis of NOC-induced carcinogenesis. We conclude that NOC exposure is associated with gene expression modifications in the colon that may increase CRC risk in humans. Study 2: Red meat intake-induced increases in fecal water genotoxicity correlate with pro-carcinogenic gene expression changes in the human colon Study 2: Red meat consumption is associated with an increased colorectal cancer (CRC) risk, which may be due to an increased endogenous formation of genotoxic N-nitroso compounds (NOCs). To assess the impact of red meat intake on potential risk factors of CRC, we investigated the effect of a 7-day dietary red meat intervention in human subjects on endogenous NOC formation and fecal water genotoxicity in relation to transcriptomic changes induced in colonic tissue. In order to evaluate the potential effect of an inflamed colon on endogenous nitrosation, the study population consisted of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) control subjects without inflammation. The intervention had no effect on fecal NOC formation but fecal water genotoxicity significantly increased in response to red meat intake. Since IBD patients showed no difference in fecal NOC formation or fecal water genotoxicity levels as compared to IBS controls, for transcriptomic analyses, all subjects were grouped together. Genes significantly correlating with the increase in fecal water genotoxicity were involved in biological pathways indicative of genotoxic effects, including modifications in DNA damage, cell cycle, and apoptosis pathways. Moreover, WNT signaling and nucleosome remodeling pathways were modulated that are known to play a part in the carcinogenic process in the human colon. These results are in line with a possible oxidative effect of dietary heme. We conclude that the gene expression changes identified in this study corroborate the genotoxic potential of diets high in red meat and point towards a possible risk of CRC development in humans. The study investigated transcription levels in human colon biopsies obtained during a colonoscopic exam in 32 subjects suffering from either inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS). IBS patients served as control patients for comparison with IBD patients (see Study 1). 12 of these patients (6 IBD and 6 IBS) also followed a 7-day diet high in red meat (300 grams/day) after which a second colonscopic exam was performed to obtain colon biopsies to investigate the effect of the red meat intervention (Study 2). For each subject, cRNA copies of mRNA isolated from the colon biopsies were labeled with one dye (Cy3) and each sample was hybridized on a separate array. One replicate per subject or before/after red meat intervention (so 44 arrays in total, i.e. 20 before patients and 12 before and after patients).
2011-02-01 | E-GEOD-25220 | biostudies-arrayexpress
Project description:Purposes: To investigate the epigenetic mechanism of IBS-D(Irritable Bowel Syndrome with Diarrhea) by tRF & tiRNA sequencing in intestinal biopsies of IBS-D patients and healthy volunteers Methods: Five IBS-D and five healthy volunteers were screened, and biopsies were taken under colonoscopy. Small RNA sequencing was performed on Illumina NexSeq instrument Results:If P < 0.05, fold change > 1.5 as the cutoff, there were 14 up-regulated tRFs & tiRNAs and 14 down-regulated tRFs & tiRNAs. Conclusions:There were 14 up-regulated tRFs & tiRNAs and 14 down-regulated tRFs & tiRNAs in intestinal tissues of IBS-D .
2023-11-04 | GSE166405 | GEO
Project description:Micro-inflammation and gut dysfunction are features of diarrhea-irritable bowel syndrome (d-IBS) patients, although the underlying interacting molecular mechanisms remain mostly unknown. Therefore, we aimed to identify critical networks and signaling pathways active in chronic diarrhea-associated inflammation. Experiment Overall Design: Healthy volunteers and d-IBS patients were studied. Jejunal biopsies were subjected to chip analysis (Affymetrix Human Genome U133 Plus 2.0 GeneChips).
2009-02-21 | E-GEOD-14841 | biostudies-arrayexpress
Project description:Increased numbers of mast cells and their products have been linked to symptom onset and severity in patients with chronic diarrhea and abdominal pain. Although mast-cell inhibition ameliorates clinical manifestations and reduces mucosal inflammation, underlying molecular mechanisms remain unknown. Experiment Overall Design: Diarrhea-irritable bowel syndrome (d-IBS) patients were studied at baseline, or 6 months after natural evolution (control) or oral cromoglycate treatment. Jejunal biopsies were subjected to chip analysis (Affymetrix Human Genome U133 Plus 2.0 GeneChips).
2009-02-21 | E-GEOD-14842 | biostudies-arrayexpress
Project description:Irritable Bowel Syndrome (IBS) is a disorder of the gut-brain axis, characterized by altered gut function and frequent psychiatric co-morbidity. Although altered intestinal microbiome profiles have been documented, their relevance to the clinical expression of IBS is unknown. To evaluate a functional role of the microbiota, we colonized germ-free mice with fecal microbiota from healthy controls or IBS patients with accompanying anxiety, and monitored gut function and behavior. Mouse microbiota profiles clustered according to their human donors. Despite having taxonomically similar composition as controls, mice with IBS microbiota had distinct serum metabolomic profiles related to neuro- and immunomodulation. Mice with IBS, but not control microbiota, exhibited faster gastrointestinal transit, intestinal barrier dysfunction, innate immune activation and anxiety-like behavior. These results support the notion that the microbiota contributes to both intestinal and behavioral manifestations of IBS and rationalize the use of microbiota-directed therapies in ameliorating IBS.
2017-03-02 | GSE61841 | GEO
Project description:RNA transcriptomics of healthy and PI-IBS colonic biopsies
| PRJNA713829 | ENA
Project description:Study 1: Transcriptomic profiles in colon tissue from inflammatory bowel diseases patients in relation to N-nitroso compound exposure and colorectal cancer risk Study 1: N-nitroso compounds (NOC) have been suggested to play a role in human cancer development but definitive evidence is still lacking. In this study we investigated gene expression modifications induced in human colon tissue in relation to NOC exposure to gain insight in the relevance of these compounds in human colorectal cancer (CRC) development. Since there are indications that inflammation stimulates endogenous NOC formation, the study population consisted of patients with inflammatory bowel disease (IBD) and irritable bowel syndrome patients as controls without inflammation. Strong transcriptomic differences were identified in colonic biopsies from IBD patients and compared to controls that enhance the understanding of IBD pathophysiology. However, fecal NOC levels were not increased in IBD patients, suggesting that inflammation did not stimulate NOC formation. By relating gene expression changes of all subjects to fecal NOC levels, we did, however, identify a NOC exposure-associated transcriptomic response that suggests that physiological NOC concentrations may induce genotoxic responses and chromatin modifications in human colon tissue, both of which are linked to carcinogenicity. In a network analysis, chromatin modifications were linked to 11 significantly modulated histone genes, pointing towards a possible epigenetic mechanism that may be relevant in comprehending the molecular basis of NOC-induced carcinogenesis. We conclude that NOC exposure is associated with gene expression modifications in the colon that may increase CRC risk in humans. Study 2: Red meat intake-induced increases in fecal water genotoxicity correlate with pro-carcinogenic gene expression changes in the human colon Study 2: Red meat consumption is associated with an increased colorectal cancer (CRC) risk, which may be due to an increased endogenous formation of genotoxic N-nitroso compounds (NOCs). To assess the impact of red meat intake on potential risk factors of CRC, we investigated the effect of a 7-day dietary red meat intervention in human subjects on endogenous NOC formation and fecal water genotoxicity in relation to transcriptomic changes induced in colonic tissue. In order to evaluate the potential effect of an inflamed colon on endogenous nitrosation, the study population consisted of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) control subjects without inflammation. The intervention had no effect on fecal NOC formation but fecal water genotoxicity significantly increased in response to red meat intake. Since IBD patients showed no difference in fecal NOC formation or fecal water genotoxicity levels as compared to IBS controls, for transcriptomic analyses, all subjects were grouped together. Genes significantly correlating with the increase in fecal water genotoxicity were involved in biological pathways indicative of genotoxic effects, including modifications in DNA damage, cell cycle, and apoptosis pathways. Moreover, WNT signaling and nucleosome remodeling pathways were modulated that are known to play a part in the carcinogenic process in the human colon. These results are in line with a possible oxidative effect of dietary heme. We conclude that the gene expression changes identified in this study corroborate the genotoxic potential of diets high in red meat and point towards a possible risk of CRC development in humans.
2011-02-01 | GSE25220 | GEO
Project description:An investigation of gene expression changes in rectal biopsies from donors with IBS compared to controls to begin to understand this complex syndrome. To further investigate differences between IBS groups (constipation and diarrhoea predominant) (part1) and how IBS relates to bacterial infection (part2) with biopsies taken 6 months after Campylobacter jejuni infection. Part1: 18 Constipation predominant IBS subjects (IBS-C) and 27 diarrhoea predominant IBS subjects (IBS-D) compared to 21 healthy volunteers (HV). Part2: 21 Campylobacter jejuni infection (PIBD, PIBS, PINIBS) compared to 19 healthy volunteers (HV). PIBD = post Campylobacter infection with IBS (within 6 months) PIBS = post infection IBS (unknown time point and organism) PINIBS = post Campylobacter infection with no resulting IBS
2012-07-12 | E-GEOD-36701 | biostudies-arrayexpress
Project description:An investigation of gene expression changes in rectal biopsies from donors with IBS compared to controls to begin to understand this complex syndrome. To further investigate differences between IBS groups (constipation and diarrhoea predominant) (part1) and how IBS relates to bacterial infection (part2) with biopsies taken 6 months after Campylobacter jejuni infection.
2012-07-13 | GSE36701 | GEO
Project description:IBS-D is a disease with multi-factor interaction between environment, central system, gut and gene, and its pathogenesis is relatively complex. In order to find the regulation of mRNA in the pathogenesis of IBS-D, intestinal tissue samples of IBS-D patients and healthy subjects were obtained (5 IBS-D patients,5 healthy subjects)， Changes in mRNA expression profiles were detected by high-throughput sequencing.
2023-03-15 | GSE212719 | GEO