Project description:To clarify the pathological significance of CGRP in ulcerative colitis, we generated knockout mice for CGRPα and CGRPβ and analyzed colon proteome data from DDS drinking water ulcerative colitis model mice. In addition, to confirm changes in the colon over time, the colon of wild-type mice after DDS drinking was harvested over time and used for proteome data.
Project description:Experimental colitis is often used as a model for the inflammatory bowel diseases, ulcerative colitis and Crohn’s disease. Results identify the inflammatory processes during acute colitis in affected tissues from TNBS-treated susceptible 5-7 week old SJL mice. Keywords: Disease state analysis Two-condition experiment, Treated vs Non-treated. Biological replicates: 4 treated, 4 non-treated. One replicate per array.
Project description:Experimental colitis is often used as a model for the inflammatory bowel diseases, ulcerative colitis and Crohn’s disease. Results identify the inflammatory processes during acute colitis in affected tissues from TNBS-treated susceptible 5-7 week old SJL mice. Keywords: Disease state analysis
Project description:Ulcerative colitis (UC) is a multifactorial inflammatory bowel disease (IBD) with increasing incidence worldwide. Current treatments, such as NSAIDs and corticosteroids, provide partial symptom relief but are associated to significant side effects. This highlights the need for novel therapies with fewer adverse effects. Given the role of oxidative stress and inflammation in driving tissue damage during colitis, natural compounds with antioxidant and anti-inflammatory properties are promising therapeutic candidates. We identified thinned apples (TA), an agricultural by-product, as a rich source of polyphenols (TAP) with anti-inflammatory and antioxidant activities in a cell-based model of inflammation. This study evaluates TAP’s therapeutic potential in a DNBS-induced colitis mouse model using label-free quantitative proteomics. Proteomic analysis revealed modulation of several key pathways influenced by TAP treatment, including: (i) activation of antioxidant defence mechanisms; (ii) reversal of DNBS-induced pathways, specifically ferroptosis and heme toxicity; (iii) suppression of immune responses; and (iv) reduction of ulcerative conditions with downregulation of proteins involved in coagulation, inflammation, and angiogenesis. Overall, TAP demonstrated significant therapeutic potential by targeting oxidative stress and inflammation, suggesting its use as a polyphenol-rich extract in health products for UC treatment. Furthermore, utilizing TA as a bioactive extract represents an innovative approach for industrial applications in therapeutic agent production.
Project description:Pre- and post-hyperbaric oxygen sequencing of mucosal biopsies of ulcerative colitis patients to understand host response to hyperoxia
Project description:Association between the microbiome, IBD and liver diseases are known, yet cause and effect remain elusive. By connecting human microphysiological systems of the gut, liver and circulating Treg/Th17 cells, we modeled progression of ulcerative colitis (UC) ex vivo. We show that microbiome-derived short-chain fatty acids (SCFA) may either improve or worsen disease severity, depending on the activation state of CD4 T cells. Employing a multiomic approach, we found SCFA reduced innate activation of the UC gut and increased hepatic metabolism. However, during acute T cell-mediated inflammation, SCFA exacerbate CD4 T cell effector function leading to gut barrier disruption and liver damage. These paradoxical findings underscore the emerging utility of human physiomimetic technology in combination with systems immunology to study causality and temporal facets of gut-liver axis related diseases where animal models might leave ambiguity.
Project description:Ulcerative Colitis is an autoimmune inflammatory bowel disease that causes chronic inflammation in the colon and the rectum. Althoung extensively researched, the underlying molecular mechanisms of Ulcerative Colitis remain elusive. Especially, there is a lack of understanding about regulatory non-coding miRNA expression during Ulcerative Colitis. Therefore, we performed high-throughput miRNA profiling of colon tissue biopsies from XX patients with active Ulcerative Colitis, XX patients with quiescent Ulcerative Colitis and XX Symptomatic Control individuals.
Project description:The gut microbiome is significantly altered in inflammatory bowel diseases, but the basis of these changes is not well understood. We have combined metagenomic and metatranscriptomic profiling of the gut microbiome to assess changes to both bacterial community structure and transcriptional activity in a mouse model of colitis. Gene families involved in microbial resistance to oxidative stress, including Dps/ferritin, Fe-dependent peroxidase and glutathione S-transferase, were transcriptionally up-regulated in colitis, implicating a role for increased oxygen tension in gut microbiota modulation. Transcriptional profiling of the host gut tissue and host RNA in the gut lumen revealed a marked increase in the transcription of genes with an activated macrophage and granulocyte signature, suggesting the involvement of these cell types in influencing microbial gene expression. Down-regulation of host glycosylation genes further supports a role for inflammation-driven changes to the gut niche that may impact the microbiome. We propose that members of the bacterial community react to inflammation-associated increased oxygen tension by inducing genes involved in oxidative stress resistance. Furthermore, correlated transcriptional responses between host glycosylation and bacterial glycan utilisation support a role for altered usage of host-derived carbohydrates in colitis. Complementary transcription profiling data from the mouse hosts have also been deposited at ArrayExpress under accession number E-MTAB-3590 ( http://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-3590/ ).