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.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: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: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
Project description:Akkermansia muciniphila, a bacterium, is associated with good health, but data are lacking whether it confers health benefits on children in low income countries and by which mechanisms. In a case-control study of children <5 years old with (n=1717) or without (n=1524) diarrhea, the presence of A. muciniphila reduces the odds ratio of symptoms of diarrhea from six diarrheal pathogens. A. muciniphila is found more frequently among children who are growing well compared with those who are growing poorly. In silico analysis of 1487 A. muciniphila genomes revealed the presence of DNA encoding the peptide larazotide known to benefit human health by improving tight junctions. Although previously considered synthetic, we demonstrated that larazotide is secreted by A. muciniphila. Larazotide is found in the nucleus of colonic epithelial cells and its exogenous application alters gene expression. When larazotide is applied to colonic organoid cultures, the amount of mucin (MUC2) is increased significantly (p<0.005). Our analyses are consistent with A. muciniphila secreting larazotide and intestinal epithelial cells responding by increasing MUC2, potentially creating a positive feedback loop that increases mucin production, which may itself increase abundance of the mucin-metabolizing A. muciniphila. This cycle may confer positive health outcomes for children.
2021-05-25 | GSE175488 | GEO
Project description:The use of Akkermansia muciniphila as potential therapeutic intervention is receiving increasing attention. Health benefits attributed to this bacterium include an improvement of metabolic disorders and exerting anti-inflammatory effects. The abundance of A. muciniphila is associated with a healthy gut in early mid- and later life. However, the effects of A. muciniphila on a decline in intestinal health during the aging process are not investigated yet. We supplemented accelerated aging Ercc1-/Δ7 mice with A. muciniphila for 10 weeks and investigated histological, transcriptional and immunological aspects of intestinal health. The thickness of the colonic mucus layer increased about 3-fold after long-term A. muciniphila supplementation and was even significantly thicker compared to mice supplemented with Lactobacillus plantarum WCFS1. Colonic gene expression profiles pointed towards a decreased expression of genes and pathways related to inflammation and immune function, and suggested a decreased presence of B cells in colon. Total B cell frequencies in spleen and mesenteric lymph nodes were not altered after A. muciniphila supplementation. Mature and immature B cell frequencies in bone marrow were increased, whereas B cell precursors were unaffected. These findings implicate that B cell migration rather than production was affected by A. muciniphila supplementation. Gene expression profiles in ileum pointed toward a decrease in metabolic- and immune-related processes and antimicrobial peptide production after A. muciniphila supplementation. Besides, A. muciniphila decreased the frequency of activated CD80+CD273- B cells in Peyer’s patches. Additionally, the increased numbers of peritoneal resident macrophages and a decrease in Ly6Cint monocyte frequencies in spleen and mesenteric lymph nodes add evidence for the potentially anti-inflammatory properties of A. muciniphila. Altogether, we show that supplementation with A. muciniphila prevented the age-related decline in thickness of the colonic mucus layer and attenuated inflammation and immune-related processes at old age. This study implies that A. muciniphila supplementation can contribute to a promotion of healthy aging.
2019-02-20 | GSE126730 | GEO
Project description:Leber2015 - Mucosal immunity and gut
microbiome interaction during C. difficile infection
This model is described in the article:
Systems Modeling of
Interactions between Mucosal Immunity and the Gut Microbiome
during Clostridium difficile Infection.
Leber A, Viladomiu M, Hontecillas R,
Abedi V, Philipson C, Hoops S, Howard B, Bassaganya-Riera
J.
PLoS ONE 2015; 10(7): e0134849
Abstract:
Clostridium difficile infections are associated with the use
of broad-spectrum antibiotics and result in an exuberant
inflammatory response, leading to nosocomial diarrhea, colitis
and even death. To better understand the dynamics of mucosal
immunity during C. difficile infection from initiation through
expansion to resolution, we built a computational model of the
mucosal immune response to the bacterium. The model was
calibrated using data from a mouse model of C. difficile
infection. The model demonstrates a crucial role of T helper 17
(Th17) effector responses in the colonic lamina propria and
luminal commensal bacteria populations in the clearance of C.
difficile and colonic pathology, whereas regulatory T (Treg)
cells responses are associated with the recovery phase. In
addition, the production of anti-microbial peptides by inflamed
epithelial cells and activated neutrophils in response to C.
difficile infection inhibit the re-growth of beneficial
commensal bacterial species. Computational simulations suggest
that the removal of neutrophil and epithelial cell derived
anti-microbial inhibitions, separately and together, on
commensal bacterial regrowth promote recovery and minimize
colonic inflammatory pathology. Simulation results predict a
decrease in colonic inflammatory markers, such as neutrophilic
influx and Th17 cells in the colonic lamina propria, and length
of infection with accelerated commensal bacteria re-growth
through altered anti-microbial inhibition. Computational
modeling provides novel insights on the therapeutic value of
repopulating the colonic microbiome and inducing regulatory
mucosal immune responses during C. difficile infection. Thus,
modeling mucosal immunity-gut microbiota interactions has the
potential to guide the development of targeted fecal
transplantation therapies in the context of precision medicine
interventions.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000583.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
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.
2024-09-02 | BIOMD0000000583 | BioModels