Ontology highlight
ABSTRACT:
PROVIDER: PRJNA756439 | ENA |
REPOSITORIES: ENA
Dataset's files
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| SRR15533154.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Akkermansia muciniphila is recognized as a promising probiotic that improves the symptoms of a variety of diseases. However, the role and mechanism of A. muciniphila in regulating intestinal homeostasis remain to be explored. Here, we discovered that A. muciniphila was dramatically increased during colitis recovery, and its colonization greatly increased goblet cells to protect the intestinal barrier in mice. Amuc_0904, a previously uncharacterized A. muciniphila outer membrane protein, was identified to induce goblet cell differentiation.
2025-02-05 | GSE288821 | GEO
Project description:Akkermansia muciniphila is recognized as a promising probiotic that improves the symptoms of a variety of diseases. However, the role and mechanism of A. muciniphila in regulating intestinal homeostasis remain to be explored. Here, we discovered that A. muciniphila was dramatically increased during colitis recovery, and its colonization greatly increased goblet cells to protect the intestinal barrier in mice. Amuc_0904, a previously uncharacterized A. muciniphila outer membrane protein, was identified to induce goblet cell differentiation.We want to find the receptors that 904 interacts with cells to explore the detailed mechanism.
2024-09-02 | PXD055466 | Pride
Project description:The mucosal epithelium plays a key role in regulating immune homeostasis. Dysregulation of epithelial barrier function is associated with mucosal inflammation. Expression of claudin-2, a pore-forming tight junction protein, is highly upregulated during inflammatory bowel disease (IBD) and, due to its association with epithelial permeability, has been postulated to promote inflammation. Furthermore, claudin-2 also regulates colonic epithelial cell proliferation and intestinal nutrient absorption. However, the precise role of claudin-2 in regulating colonic epithelial and immune homeostasis remains unclear. Here, we demonstrate, using Villin-Claudin-2 transgenic (Cl-2TG) mice, that increased colonic claudin-2 expression unexpectedly protects mice against experimentally induced colitis and colitis-associated cancer. Notably, Cl-2TG mice exhibited increased colon length and permeability as compared with wild type (WT) littermates. However, despite their leaky colon, Cl-2TG mice subjected to experimental colitis were immune compromised, with reduced induction of TLR-2, TLR-4, Myd-88 expression and NF-kB and STAT3 activation. Most importantly, colonic macrophages in Cl-2TG mice exhibited an anergic phenotype. Claudin-2 overexpression also increased colonocyte proliferation and provided protection against colitis-induced colonocyte death. Taken together, our findings have revealed a critical role of claudin-2 in regulating colonic homeostasis, suggesting novel therapeutic strategies for inflammatory conditions of the gastrointestinal tract. 8-10 weeks old male Villin-Claudin-2 transgenic mice and WT littermates were provided either normal drinking water (control) or Dextran Sodium Sulfate (DSS: 4% w/v) for 10 days. 3 replicates each.
2013-09-15 | E-GEOD-46006 | biostudies-arrayexpress
Project description:The impacts of individual commensal microbes on immunity and disease can differ dramatically depending on the surrounding microbial context, yet the specific bacterial combinations that dictate divergent immunological outcomes in humans remain largely undefined. We isolated a novel Allobaculum strain from an inflammatory bowel disease (IBD) patient that elicited antigen-specific mucosal and systemic antibody responses at homeostasis and exacerbated colitis in gnotobiotic mice. Using human microbiota-associated mouse models, we uncovered an inverse correlation between Allobaculum and the taxonomically-divergent immunostimulatory species Akkermansia muciniphila, which was also reflected in human cohorts. Co-colonization with Allobaculum and A. muciniphila reprogrammed the immune responses evoked by each microbe on its own, ameliorated Allobaculum-induced colitis, and blunted A. muciniphila-induced T and B cell responses. These studies thus identify a reciprocal ‘epistatic’ interaction between unique immunostimulatory human gut bacteria and establish a generalizable framework to dissect the role of microbial context in strain-specific microbial effects on human disease.
2021-12-01 | GSE179165 | GEO
Project description:Dedicator of cytokinesis 2 (Dock2), a guanine nucleotide exchange factor that activates the small GTPase Rac1, plays a crucial role in host defense and cytoskeletal regulation. While Dock2 is predominantly expressed in intestinal T cells and is significantly upregulated in patients with inflammatory bowel diseases (IBD), its precise role in intestinal inflammation remains obscure. In this study, we demonstrate that systemic Dock2-deficient mice and T cell-specific Dock2 conditional knockout (Dock2-cKO) mice exhibit exacerbated chemically induced colitis compared to wild-type (WT) controls. Dock2 deficiency led to a substantial reduction in both total and IFN-γ-producing CD8+ T cells, accompanied by elevated colonic IL-22 levels, increased expression of Reg3γ and Reg3β antimicrobial peptides (AMPs), and diminished colonization by Verrucomicrobia, particularly Akkermansia muciniphila (A. muciniphila), at steady state. The expression of Reg3γ&β was suppressed in IL-22- and RORγt-deficient mice, and these AMPs exhibited antimicrobial activity against the expansion and intestinal colonization of A. muciniphila. Co-housing Dock2-cKO mice with WT mice or reintroducing A. muciniphila restored colitis severity to levels comparable to WT mice. The inhibitor against Dock2-Rac1 signaling significantly impaired IFN-γ production in both murine and human T cells. Furthermore, IFN-γ suppressed IL-22 expression induced by IL-1, likely via aryl hydrocarbon receptor (Ahr)-dependent but RORγt-independent mechanisms. Collectively, these findings reveal a critical Dock2-mediated axis linking T cell type 1 responses, IL-22–Reg3 AMPs, and commensal microbiota, particularly A. muciniphila. Targeting Dock2 and its downstream pathways may offer novel therapeutic strategies for IBD and other mucosal-associated immune disorders.
2026-06-10 | GSE288392 | GEO
Project description:The mucosal epithelium plays a key role in regulating immune homeostasis. Dysregulation of epithelial barrier function is associated with mucosal inflammation. Expression of claudin-2, a pore-forming tight junction protein, is highly upregulated during inflammatory bowel disease (IBD) and, due to its association with epithelial permeability, has been postulated to promote inflammation. Furthermore, claudin-2 also regulates colonic epithelial cell proliferation and intestinal nutrient absorption. However, the precise role of claudin-2 in regulating colonic epithelial and immune homeostasis remains unclear. Here, we demonstrate, using Villin-Claudin-2 transgenic (Cl-2TG) mice, that increased colonic claudin-2 expression unexpectedly protects mice against experimentally induced colitis and colitis-associated cancer. Notably, Cl-2TG mice exhibited increased colon length and permeability as compared with wild type (WT) littermates. However, despite their leaky colon, Cl-2TG mice subjected to experimental colitis were immune compromised, with reduced induction of TLR-2, TLR-4, Myd-88 expression and NF-kB and STAT3 activation. Most importantly, colonic macrophages in Cl-2TG mice exhibited an anergic phenotype. Claudin-2 overexpression also increased colonocyte proliferation and provided protection against colitis-induced colonocyte death. Taken together, our findings have revealed a critical role of claudin-2 in regulating colonic homeostasis, suggesting novel therapeutic strategies for inflammatory conditions of the gastrointestinal tract.
2013-09-15 | GSE46006 | GEO
Project description:Akkermansia muciniphila proteome analysis by label-free mass spectrometry showed the upregulation of three sulfatases (Amuc0491, Amuc1655 and Amuc1182) when grown on colonic mucins versus gastric mucins.
2026-08-04 | PXD078370 | Pride
Project description:Kees2018 - Genome-scale constraint-based
model of the mucin-degrader Akkermansia
muciniphila
This model is described in the article:
Model-driven design of a
minimal medium for Akkermansia muciniphila confirms mucus
adaptation.
van der Ark KCH, Aalvink S,
Suarez-Diez M, Schaap PJ, de Vos WM, Belzer C.
Microb Biotechnol 2018 Jan; :
Abstract:
The abundance of the human intestinal symbiont Akkermansia
muciniphila has found to be inversely correlated with several
diseases, including metabolic syndrome and obesity.
A. muciniphila is known to use mucin as sole carbon and
nitrogen source. To study the physiology and the potential for
therapeutic applications of this bacterium, we designed a
defined minimal medium. The composition of the medium was based
on the genome-scale metabolic model of A. muciniphila and
the composition of mucin. Our results indicate that
A. muciniphila does not code for GlmS, the enzyme that
mediates the conversion of fructose-6-phosphate (Fru6P) to
glucosamine-6-phosphate (GlcN6P), which is essential in
peptidoglycan formation. The only annotated enzyme that could
mediate this conversion is Amuc-NagB on locus Amuc_1822. We
found that Amuc-NagB was unable to form GlcN6P from Fru6P at
physiological conditions, while it efficiently catalyzed the
reverse reaction. To overcome this inability,
N-acetylglucosamine needs to be present in the medium for
A. muciniphila growth. With these findings, the
genome-scale metabolic model was updated and used to accurately
predict growth of A. muciniphila on synthetic media. The
finding that A. muciniphila has a necessity for GlcNAc,
which is present in mucin further prompts the adaptation to its
mucosal niche.
This model is hosted on
BioModels Database
and identified by:
MODEL1710040000.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2021-02-15 | MODEL1710040000 | BioModels
Project description:Despite accepted health benefits of dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a gnotobiotic model, in which mice were colonized with a synthetic human gut microbiota, we elucidated the functional interactions between dietary fiber, the gut microbiota and the colonic mucus barrier, which serves as a primary defence against pathogens. We show that during chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation promoted greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium, but only in the presence of a fiber-deprived microbiota that is pushed to degrade the mucus layer. Our work reveals intricate pathways linking diet, gut microbiome and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics. Germ-free mice (Swiss Webster) were colonized with synthetic human gut microbiota comprising of 14 species belonging to five different phyla (names of bacterial species: Bacteroides thetaiotaomicron, Bacteroides ovatus, Bacteroides caccae, Bacteroides uniformis, Barnesiella intestinihominis, Eubacterium rectale, Marvinbryantia formatexigens, Collinsella aerofaciens, Escherichia coli HS, Clostridium symbiosum, Desulfovibrio piger, Akkermansia muciniphila, Faecalibacterium prausnitzii and Roseburia intestinalis). These mice were fed either a fiber-rich diet or a fiber-free diet for about 6 weeks. The mice were then sacrificed and their cecal tissues were immediately flash frozen for RNA extraction. The extracted RNA was subjected to microarray analysis based on Mouse Gene ST 2.1 strips using the Affy Plus kit. Expression values for each gene were calculated using robust multi-array average (RMA) method.
2016-11-21 | GSE79067 | GEO
Project description:Athough anti-TNF therapies can be used to treat colitis associated with inflammatory bowel disease, in mice the loss of the TNF receptor TNFR1 (Tnfrsf1a) in the Il10-/- spontaneous colitis background results in acceleration of disease onset. Whereas Il10-/- mice on the Bl/6 background are relatively protected from colitis throughout life, Il10-/- Tnfr1-/- mice develop colitis beginning at 4 wks of age. Their disease results in nearly 50% mortality by 12 wks of age. Strikingly, Tnfr1-/- mice (with functional IL-10) exhibit evidence of mucosal dysfunction at 4 and 12 wks of age. These mucosal abnormalities include loss of barrier integrity, increased epithelial cell proliferation, crypt malformations, and increased immune cell infiltrate. Because of the early onset of mucosal abnormalities in Tnfr1-/- mice, with or without IL-10 expression, we hypothesized that TNFR1 plays important roles in colonic mucosal function in early life, prior to weaning. To test this hypothesis, we profiled, using mRNA-Seq, the colonic transcriptomes from wildtype and Tnfr1-/- mice at 2 wks of age. The results demonstrate that Tnfr1-/- mice have important gene expression changes, including reduced expression of Il1b, a marker of the proinflammatory "weaning reaction" that is required for establishment of mucosal tolerance in later life. TNFR1 therefore has key roles in colonic mucosal homeostasis in early life.
2020-08-05 | GSE155654 | GEO