Ceramic
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PROVIDER: PRJEB52306 | ENA |
REPOSITORIES: ENA
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Project description:Clinical COPD, characterised by intermittent and infective exacerbations, lacks cellular model systems for the study of host-pathogen relationships. We establish nasopharyngeal and bronchial organoids from COPD patients and healthy individuals. In contrast to healthy organoids, COPD organoids demonstrate the hallmark goblet cell hyperplasia phenotype with reduced ciliary beat frequency, leading to impaired mucociliary clearance. By single-cell transcriptome analysis, smooth trajectory of cellular differentiation is disrupted in COPD organoids when compared to non-diseased, and functional pathways involved in the development and progression of COPD including mitochondrial dysfunction and sirtuin signalling are activated in the COPD model.
2022-11-10 | GSE186017 | GEO
Project description:Colibactin, a bacterial genotoxin produced by E. coli harboring the pks genomic island, induces cytopathic effects such as DNA breaks, cell cycle arrest and apoptosis. Patients with a colonic dysfunction due to inflammatory bowel disease such as ulcerative colitis have an elevated likelihood of carrying pks+ E. coli in their colon microbiota but it is not clear whether and how they contribute to the pathogenesis of colitis. Using a gnotobiotic mouse model, we show that pks+ E. coli do not affect colonic integrity under homeostatic conditions, with the microbiota remaining separated from the epithelium by a mucus barrier. However, upon chemical disruption of this barrier by DSS, the microbes gain direct access to the epithelium, causing severe epithelial injury, and development of colitis, while mice colonized with an isogenic ΔclbR mutant incapable of producing colibactin suffer significantly less pronounced effects. While ΔclbR-colonized animals show efficient recovery of the mucus barrier and crypt homeostasis, recovery in WT-colonized mice is impaired. Instead, the mucosa remains in a chronic regenerative state characterized by high proliferation and impaired differentiation of enterocytes and goblet cells, preventing the re-establishment of a functional barrier. In turn, pks+ E. coli remain in direct contact with the epithelium, perpetuating the process and triggering chronic mucosal inflammation that morphologically and transcriptionally resembles human ulcerative colitis. It is characterized by high levels of stromal R-spondin 3. Genetic overexpression of R-spondin 3 in colon myofibroblasts is sufficient to mimic this chronic regenerative state, resulting in barrier disruption and expansion of E. coli. Together, our data reveal that pks+ E. coli are pathobionts that upon contact with the epithelium promote severe injury and interfere with recovery, initiating chronic tissue dysfunction and inflammation.
2023-07-10 | GSE205403 | GEO
Project description:The role of environmental factors and gender disparities as determinants of health is incontrovertible. In the digestive sphere, it is noteworthy that one of the most prevalent diseases such as irritable bowel syndrome (IBS) has a predominance in females. The origin of IBS is related to mucosal microinflammation phenomena, psychosocial stress, and in the last years, alterations in gut microbiota. Recent observations from our group in healthy subjects, demonstrate that both chronic psychosocial stress, and female gender per se determine a significant intestinal epithelial barrier dysfunction in response to intercurrent stimuli, which, in susceptible individuals, could result in an early stage in the development of more lasting changes and the onset of clinical manifestations of IBS. Although the intimate mechanisms involved in stress-induced intestinal pathophysiology are not well known, diverse studies suggest that gut microbiota alteration, through epigenetic modifications of the main stress-mediators could be one of them. However, solid scientific evidence demonstrating the influence of stress on gut microbiota and epigenetics of the main stress-mediators is missing. Therefore, we want to investigate and characterize gender-dependent epigenetic modifications involved in intestinal barrier dysfunction in response to acute stress. The identification of gender-dependent abnormal epigenetic patterns related to female gender dysfunction can make a breakthrough in the understanding of the pathophysiology of the regulation of intestinal permeability, and promote positive diagnostic and therapeutic future progress in IBS.
2024-02-15 | E-MTAB-10158 | biostudies-arrayexpress
Project description:Background: The etiology of Inflammatory Bowel Disease (IBD) is unclear but involves both genetics and environmental factors, including the gut microbiota. Indeed, exacerbated activation of the gastrointestinal immune system toward the gut microbiota occurs in genetically susceptible hosts and under the influence of the environment. For instance, a majority of IBD susceptibility loci lie within genes involved in immune responses, such as caspase recruitment domain member 9 (Card9). However, the relative impacts of genotype versus microbiota on colitis susceptibility in the context of CARD9 deficiency remain unknown. Results: Card9 gene directly contributes to recovery from dextran sodium sulfate (DSS)-induced colitis by inducing the colonic expression of the cytokine IL-22 and the antimicrobial peptides Reg3 and Reg3 independently of the microbiota. On the other hand, Card9 is required for regulating the microbiota capacity to produce AhR ligands, which leads to the production of IL-22 in the colon, promoting recovery after colitis. In addition, cross-fostering experiments showed that five weeks after weaning, the microbiota transmitted from the nursing mother before weaning had a stronger impact on the tryptophan metabolism of the pups than the pups' own genotype. Conclusions: These results show the role of CARD9 and its effector IL-22 in mediating recovery from DSS-induced colitis in both microbiota-independent and microbiota-dependent manners. Card9 genotype modulates the microbiota metabolic capacity to produce AhR ligands, but this effect can be overridden by the implantation of a WT or healthy microbiota before weaning. It highlights the importance of the weaning reaction occurring between the immune system and microbiota for the host metabolism and immune functions throughout life. A better understanding of the impact of genetics on microbiota metabolism is key to developing efficient therapeutic strategies for patients suffering from complex inflammatory disorders.
2024-05-01 | GSE262585 | GEO
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:Intracerebral hemorrhage (ICH) induces alterations in the gut microbiota composition, significantly impacting neuroinflammation post-ICH. However, the impact of gut microbiota absence on neuroinflammation following ICH-induced brain injury remain unexplored. Here, we observed that the gut microbiota absence was associated with reduced neuroinflammation, alleviated neurological dysfunction, and mitigated gut barrier dysfunction post-ICH. In contrast, recolonization of microbiota from ICH-induced SPF mice by transplantation of fecal microbiota (FMT) exacerbated brain injury and gut impairment post-ICH. Additionally, microglia with transcriptional changes mediated the protective effects of gut microbiota absence on brain injury, with Apoe emerging as a hub gene. Subsequently, Apoe deficiency in peri-hematomal microglia was associated with improved brain injury. Finally, we revealed that gut microbiota influence brain injury and gut impairment via gut-derived short-chain fatty acids (SCFA).
2024-05-13 | GSE266602 | GEO
Project description:Abstract. Background: The cause of ulcerative colitis (UC) is not yet fully understood. Previous research has pointed towards a potential role for mutations in NOD2 in promoting the onset and progression of inflammatory bowel disease (IBD) by altering the microbiota of the gut. However, the relationship between toll-like receptor 4 (TLR4) and gut microbiota in IBD is not well understood. To shed light on this, the interaction between TLR4 and gut microbiota was studied using a mouse model of IBD. Methods: To examine the function of TLR4 signaling in intestinal injury repair, researchers developed Dextran Sulfate Sodium Salt (DSS)-induced colitis and injury models in both wild-type (WT) mice and TLR4 knockout (TLR4-KO) mice. To assess changes in the gut microbiota, 16S rRNA sequencing was conducted on fecal samples from both the TLR4-KO and WT enteritis mouse models. Results: The data obtained depicted a protective function of TLR4 against DSS-induced colitis. The gut microbiota composition was found to vary considerably between the WT and TLR4-KO mice groups as indicated by β-diversity analysis and operational taxonomic units (OTUs) cluster. Statistical analysis of microbial multivariate variables depicted an elevated abundance of Escherichia coli/Shigella, Gammaproteobacteria, Tenerlcutes, Deferribacteres, Enterobacteria, Rikenellaceae, and Proteobacteria in the gut microbiota of TLR4-KO mice, whereas there was a considerable reduction in Bacteroidetes at five different levels of the phylogenetic hierarchy including phylum, class, order, family, and genus in comparison with the WT control. Conclusion: TLR4 may protect intestinal epithelial cells from damage in response to DSS-induced injury by controlling the microbiota in the gut.
2023-11-01 | GSE227565 | GEO
Project description:The etiology of post-inflammatory gastrointestinal (GI) motility dysfunction, after resolution of acute symptoms of inflammatory bowel diseases (IBD) and intestinal infection, is largely unknown. Here, using an established mouse model of experimental enteritis, we show that enhancement of smooth muscle cell (SMC) contraction by interleukin (IL)-17A may be involved in postinflammatory GI hypermotility. To examine the effect of IL-17 in the small intestinal smooth muscle, we used whole genome microarray expression profiling to find out the genes which respond to IL-17 stimulus. The smooth muscle strips were peeled off from mouse small intestine and incubated 24h with or without IL-17. And we also examined the effect of 6-shogaol, which is one of the ingredients of Japanese traditional medicine for intestinal mortor disorder, Daikenchuto, in IL-17 stimulated small intestinal smooth muscle strip. The smooth muscle strips were peeled off from mice small intestine and incubated in the culture media for 24h with or without IL-17. A part of IL-17 stimulated strips were co-incubated with 6-shogaol. Six independent experiments were performed.
2012-09-15 | E-GEOD-39573 | biostudies-arrayexpress
Project description:It is crucial to decipher the host-microbiota interactions as they are involved in intestinal homeostasis and diseases. Caspase Recruitment Domain 9 (Card9) is an inflammatory bowel disease (IBD) susceptibility gene coding for an adapter protein for innate immunity toward many microorganisms. Card9-/- mice are more susceptible to colitis induced by Citrobacter rodentium as a result of impaired of the IL-22 pathway. C. rodentium is a natural mouse pathogen widely used to model human infections with Enteropathogenic Escherichia coli and Enterohaemorrhagic E. coli. To explore the role of the gut microbiota in the susceptibility of Card9-/- mice to C. rodentium infection, we colonized WT germ-free (GF) mice with the microbiota of WT (WT-->GF) or Card9-/- (Card9-/- -->GF) mice and challenged them with C. rodentium. Card9-/- -->GF mice were more susceptible than WT-->GF mice to C. rodentium. To examine the mechanisms responsible for this defect, we compared the cecum transcriptomes of WT -->GF and Card9-/- -->GF mice before and during C. rodentium-induced colitis. The number of down-regulated and up-regulated genes on day 12 after C. rodentium infection was lower in Card9-/- -->GF mice than WT-->GF mice. Card9-/- -->GF mice showed a significant down-regulation of gut morphogenesis and wound healing pathways suggesting that recovery is impaired in Card9-/- -->GF mice after C. rodentium infection. Immune response and cell division pathways were up-regulated in WT-->GF mice but not in Card9-/- -->GF confirming the defect of global response to infection when only the Card9-/- microbiota was transferred. The most induced and differentially expressed genes between Card9-/- -->GF and WT-->GF mice on day 4 after C. rodentium infection were Reg3g (encoding REGIIIγ) and Reg3b (encoding REGIIIβ).
2017-11-25 | GSE90577 | GEO
Project description:Diarrhoeal mechanisms of the Campylobacter jejuni enteritis
| PRJNA348339 | ENA