Transcriptome study of colon epithelial cells in Reg3a-transgenic mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE64932 | GEO | 2018/01/31
REPOSITORIES: GEO
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Project description:Symbiotic interactions between humans and our communities of resident gut microbes (microbiota) play many roles in health and disease. Some gut bacteria utilize mucus as a nutrient source and can under certain conditions damage the protective barrier it forms, increasing disease susceptibility. We investigated how Ruminococcus torques—a known mucin-degrader that remains poorly studied despite its implication in inflammatory bowel diseases (IBDs)— degrades mucin glycoproteins or their component O-linked glycans to understand its effects on the availability of mucin-derived nutrients for other bacteria. We found that R. torques utilizes both mucin glycoproteins and released oligosaccharides from gastric and colonic mucins, degrading these substrates with a panoply of mostly constitutively expressed, secreted enzymes. Investigation of mucin oligosaccharide degradation by R. torques revealed strong fucosidase, sialidase and b1,4-galactosidase activities. There was a lack of detectable sulfatase and weak β1,3-galactosidase degradation, resulting in accumulation of glycans containing these structures on mucin polypeptides. While the Gram-negative symbiont, Bacteroides thetaiotaomicron grows poorly on mucin glycoproteins, we demonstrate a clear ability of R. torques to liberate products from mucins, making them accessible to B. thetaiotaomicron. This work underscores the diversity of mucin-degrading mechanisms in different bacterial species and the probability that some species are contingent on others for the ability to more fully access mucin-derived nutrients. The ability of R. torques to directly degrade a variety of mucin and mucin glycan structures and unlock released glycans for other species suggests that it is a keystone mucin degrader, which may contribute to its association with IBD.
2024-06-19 | GSE262875 | GEO
Project description:In a healthy gut, microbes are often aggregated with host mucus, yet the molecular basis for this organization and its impact on intestinal health are unclear. Mucus is a viscous physical barrier separating resident microbes from epithelia, but also provides glycan cues that regulate microbial behaviors. Here, we describe a mucin-sensing pathway in an Aeromonas symbiont of zebrafish, Aer01. In response to the mucin-associated glycan N-acetylglucosamine, a sensor kinase regulates expression of an aggregation-promoting adhesin we named MbpA. Upon MbpA disruption, Aer01 colonizes to normal levels, but is largely planktonic and more immunogenic. Increasing cell surface MbpA rescues these traits. MbpA-like adhesins are common in human-associated bacteria and expression of an Akkermansia muciniphila MbpA-like adhesin in MbpA-deficient Aer01 restores lumenal aggregation and reverses its pro-inflammatory character. Our work demonstrates how resident bacteria use mucin glycans to modulate behaviors congruent with host health.
2023-07-03 | GSE236092 | GEO
Project description:We use high-throughput sequencing to profile the response of oral commensal pathogen Streptococcus mutans to mucins protein polymers (human MUC5B mucins) and soluble mucin glycans (human MUC5B glycans and porcine MUC5AC glycans). We find that mucins and their glycans alter the regulation of dozens of S. mutans genes, specifically downregulating competence-associated quorum sensing genes. The transcriptional responses induced by MUC5B mucins, MUC5B glycans, and MUC5AC glycans are highly correlated.
2021-01-01 | GSE163258 | GEO
Project description:Gene expression profiles of Bacteroides thetaiotaomicron in vitro during growth on host mucosal polysaccharides as sole carbon sources. All substrates in this series are derived from porcine gastric mucin and include mucin O-glycans and glycosaminoglycans.
2008-11-21 | GSE11944 | GEO
Project description:Background; MUC2 mucin produced by intestinal goblet cells is the major component of the intestinal mucus barrier. MUC2 homo-oligomerizes intracellularly into large secreted polymers which give mucus its viscous properties. The inflammatory bowel disease (IBD) ulcerative colitis is characterized by depleted goblet cells and a reduced mucus layer, whereas goblet cells and the mucus layer are increased in the other major inflammatory bowel disease, Crohnâs disease. Methods and Findings; By murine N-ethyl-N-nitrosourea-mutagenesis we identified two distinct non-complementing missense mutations in Muc2 exons encoding N- and C-terminal homo-oligomerization domains causing an ulcerative colitis-like phenotype. Both strains developed mild spontaneous distal intestinal inflammation, chronic diarrhea, rectal bleeding and prolapse, increased susceptibility to acute and chronic colitis induced by a luminal toxin, aberrant Muc2 biosynthesis, smaller goblet cell thecae (less stored mucin) and a diminished mucus barrier. Enhanced local production of IL-1beta, TNF-alpha and IFN-gamma was seen in the distal colon. The number of leukocytes within mesenteric lymph nodes was increased five-fold and leukocytes cultured in vitro produced both Th1 and Th2 cytokines (IFN-gamma, TNF-alpha and IL-13). Intestinal permeability was increased and the luminal bacterial flora were more heavily coated with immunoglobulin as occurs in IBD. This pathology was accompanied by accumulation of the Muc2 precursor and ultrastructural and biochemical evidence of endoplasmic reticulum (ER) stress in goblet cells, activation of the unfolded protein response, and altered intestinal expression of genes involved in ER stress, inflammation, apoptosis and wound repair. Expression of mutated Muc2 oligomerization domains in vitro demonstrated that aberrant Muc2 oligomerization underlies the ER stress. These models show that mutations in Muc2 oligomerization domains can lead to aberrant assembly of the Muc2 complex leading to ER stress, a depleted mucus barrier and intestinal inflammation. In ulcerative colitis we demonstrate similar accumulation of non-glycosylated MUC2 precursor in goblet cells together with ultrastructural and biochemical evidence of ER stress even in non-inflamed intestinal tissue. Conclusions; The observations that mucin misfolding and ER stress lead directly to intestinal inflammation and that ER stress and goblet cell pathology occur in ulcerative colitis suggest that ER stress-related mucin depletion could be a fundamental component of the pathogenesis of colitis. Experiment Overall Design: 3 individual mice from the Eeyore, Winnie or Wild-type strains were compared as groups. An Affymetrix ID was compared between groups if the ID was Present within two of the three mice within each grouping. IDs were compared by calculating the log2 of Group One average signal divided by Group 2 average signal.
2008-04-06 | E-GEOD-9913 | biostudies-arrayexpress
Project description:The incidence and prevalence of inflammatory bowel disease (IBD) is gradually increasing. A high-fat diet (HFD) is known to disrupt intestinal homeostasis and aggravate IBD, yet the underlying mechanisms remain largely undefined. Here, a positive correlation between dietary fat intake and disease severity in both IBD patients and HFD-fed mice is observed. HFD induces a significant decrease in indole-3-acetic acid (IAA) and lead to intestinal barrier damage. Furthermore, IAA supplementation enhances the intestinal mucin sulfation and effectively alleviates colitis. Mechanistically, IAA upregulates key molecules involved in mucin sulfation, including Papss2 and Slc35b3, the synthesis enzyme and the transferase of 3'-phosphoadenosine-5'-phosphosulfate (PAPS), via the Aryl Hydrocarbon Receptor (AHR). More importantly, AHR can directly bind to the transcription start site of Papss2. Oral administration of Lactobacillus reuteri, which can produce IAA, contributes to protecting against colitis and promoting mucin sulfation, while the modified L. reuteri strain lacking the iaaM gene (LactobacillusΔiaaM) and the ability to produce IAA fails to exhibit such effects. Overall, IAA enhances intestinal mucin sulfation through AHR, contributing to the protection of intestinal homeostasis.
2024-05-26 | GSE249996 | GEO
Project description:We use high-throughput sequencing to profile the response of the opportunistic fungal pathogen Candida albicans to mucins and mucin-glycans from the mucosal niche. We find that C. albicans undergoes a genome-wide phenotypic shift in response to mucins and their attached glycans suppressing virulence-associated pathways.
2022-01-03 | GSE192826 | GEO
Project description:In 2005, we determined the glyco-gene expression profile of three normal subjects ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE27593). This led to information on the biosynthesis of mucin O-glycans and glycoproteins that may be involved in the protection of the ocular surface. The interaction of the most highly expressed glycoprotein identified by the glyco-gene chip, galectin-3, with other ligands at the ocular surface (i.e., mucin O-glycans), is now under intense study in our laboratory, and has lead to a collaboration with another group in the glycobiology field.
2011-04-29 | GSE28941 | GEO
Project description:Purpose: Examining the transcriptome of human gut bacteria (Bacteroides xylanisolvens/Bacteroides ovatus) that grow on mucin O-linked glycans as a sole carbon source Methods: Strains were grown on 10 mg/ml mucin O-linked glycans (MOG) or 5 mg/ml glucose as a sole carbon source in vitro. Fold change was calculated as MOG over glucose. Once cells reached an optical density corresponding to mid-log phase growth, RNA was isolated and rRNA depleted. Samples were multiplexed for sequencing on the Illumina HiSeq platform at the University of Michigan Sequencing Core. Data was analyzed using Arraystar software (DNASTAR, Inc.) Genes with significant up- or down-regulation were determined by the following criteria: genes with an average fold-change >10-fold and biological replicates with a normalized expression level >1% of the overall average RPKM expression level. Results: We identified genes activated in response to mucin O-linked glycans from Bacteroides xylanisolvens/Bacteroides ovatus strains
2020-12-01 | GSE155869 | GEO
Project description:Analysis of mucin-type O-glycan regulation of gene expression in murine intestinal epithelial cells isolated from a mouse. The hypothesis tested in the current study was that loss of Cosmc (by Cre/Lox: Vil-Cre+ X Cosmcflox/+), which is required for core 1-based O-glycan extension, influences gene expression. Transcripts from colorectum and from small intestine were compared to also evaluate whether O-glycans control different genes in different regions of the gut. We had particular interest in identifying transcripts or pathways important in regulating the microbiota or influencing intestinal inflammation. Results provide important information on how cell surface glycosylation controls gene transcription in in vivo.
2016-12-18 | GSE84416 | GEO