Project description:Irritable bowel syndrome (IBS) patients often experience meal associated symptoms. Our objective was to determine small intestinal mechanisms of lipid-induced symptoms and rectal hypersensitivity in IBS based on RNA-seq.
Project description:A subset of post-infection irritable bowel syndrome (PI-IBS) patients have elevated, or high fecal proteolytic activity (PA). Fecal PA has been shown to correlate with increased symptom severity as well as lower quality of life scores, increased fecal output and increased intestinal permeability. To address the underlying mechanisms of barrier disruption as a consequence of high fecal PA, colonic biopsies were collected from healthy individuals PI-IBS patients (n=11). Individuals diagnosed with PI-IBS were further divided in to 2 subgroups, high PA and low PA as defined by the PA in matched fecal samples. RNA was extracted from the biopsies for bulk RNA sequencing to understand transcriptional differences between healthy and high PA PI-IBS patients as well as high PA and Low PA PI-IBS patients.
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 miRNA 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 miRNA expression profiles were detected by high-throughput sequencing.
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).
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.
Project description:IBS: Patients who have undergone a diagnostic program for gastrointestinal symptoms and where the diagnosis irritable bowel syndrome was reached. UC: Patients with well-diagnosed ulcerative colitis Keywords: other
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 .
Project description:Background: Luminal proteases have been implicated in epithelial barrier dysfunction and visceral hypersensitivity in irritable bowel syndrome (IBS), yet their impact on the enteric nervous system (ENS), the principal regulator of gastrointestinal function, remains unknown. We investigated whether faecal mediators differentially activate enteric neurons across IBS subtypes and whether proteolytic and proteomic profiles explain neuronal phenotypes. Methods: The effects of faecal supernatants from 21 IBS-D, 9 IBS-C patients, and 18 healthy controls on guinea pig distal colon submucous plexus neurons were assessed using a neuroimaging technique. Faecal proteolytic activities and proteomic profiles were also analyzed. Results: IBS-D and IBS-C supernatants evoked significantly stronger neuronal activation than healthy controls, demonstrating for the first time that faecal mediators directly modulate enteric neurons. In IBS-D, but not in IBS-C, effects were mediated by serine and cysteine proteases and PAR-1. Proteome analysis revealed a significant difference in 48 proteins between IBS-D and healthy controls, including several immunoglobulin components, underlying the role of microinflammation in IBS-D. Three proteins demonstrated high diagnostic performance to distinguish IBS-D from controls. Conclusion: These findings uncover a previously unrecognised luminal–neuronal communication axis in IBS and reveal fundamentally different pathological mechanisms between IBS-D and IBS-C. IBS-D is characterised by proteases and PAR-1 dependent neuronal activation and a distinct immune-enriched faecal proteome, whereas mediators in IBS-C act through protease-independent pathways. These findings establish a functional link between faecal protease activity, ENS signalling, and molecular biomarkers, highlighting new therapeutic and diagnostic avenues for subtype-specific management of IBS.
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.