Transcriptional responses of colon tissues following ex-vivo colonization with human microbiome
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE142748 | GEO | 2020/09/29
REPOSITORIES: GEO
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Project description:We analyzed the transcriptional profile of colon and small-intestinal (SI) tissues in response to ex-vivo colonization with members of the gut microbiota. Tissues were dissected from SPF or GF mice, and connected to the ex-vivo gut organ culture system. Then, microbial cultures or fecal samples were infused into the lumen, and tissues were processed in different time points, as indicated below.
2016-12-17 | GSE92471 | GEO
Project description:A subset of post-infection irritable bowel syndrome (PI-IBS) patients have elevated, or high fecal proteolytic activity (PA). Fecal PA has been shown to correlate with increased symptom severity as well as lower quality of life scores, increased fecal output and increased intestinal permeability. To address the underlying mechanisms of barrier disruption as a consequence of high fecal PA, colonic biopsies were collected from healthy individuals PI-IBS patients (n=11). Individuals diagnosed with PI-IBS were further divided in to 2 subgroups, high PA and low PA as defined by the PA in matched fecal samples. RNA was extracted from the biopsies for bulk RNA sequencing to understand transcriptional differences between healthy and high PA PI-IBS patients as well as high PA and Low PA PI-IBS patients.
2021-12-31 | GSE168759 | 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.
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2014-04-08 | BIOMD0000000583 | BioModels
Project description:Significant gut microbiota heterogeneity exists amongst UC patients though the clinical implications of this variance are unknown. European and South Asian UC patients exhibit distinct disease risk alleles, many of which regulate immune function and relate to variation in gut microbiota β-diversity. We hypothesized ethnically distinct UC patients exhibit discrete gut microbiotas with unique luminal metabolic programming that influence adaptive immune responses and relate to clinical status. Using parallel bacterial 16S rRNA and fungal ITS2 sequencing of fecal samples (UC n=30; healthy n=13), we corroborated previous observations of UC-associated depletion of bacterial diversity and demonstrated significant gastrointestinal expansion of Saccharomycetales as a novel UC characteristic. We identified four distinct microbial community states (MCS 1-4), confirmed their existence using microbiota data from an independent UC cohort, and show they co-associate with patient ethnicity and degree of disease severity. Each MCS was predicted to be uniquely enriched for specific amino acid, carbohydrate, and lipid metabolism pathways and exhibited significant luminal enrichment of metabolic products from these pathways. Using a novel in vitro human DC/T-cell assay we show that DC exposure to patient fecal water led to MCS -specific changes in T-cell populations, particularly the Th1:Th2 ratio, and that patients with the most severe disease exhibited the greatest Th2 skewing. Thus, based on ethnicity, microbiome composition, and associated metabolic dysfunction, UC patients may be stratified in a clinically and immunologically meaningful manner, providing a platform for the development of FMC-focused therapy. Fecal microbiome was assessed with Affymetrix PhyloChip arrays from patients with ulcerative colitis and healthy controls.
2016-07-25 | E-GEOD-78724 | biostudies-arrayexpress
Project description:Ulcerative Colitis fecal samples were transplanted into IL10 deficient gnotobiotic mice. Half of the mice received a protease inhibitor cocktail in their drinking water. After 8-weeks colonization the animals were studied for colonic inflammation, and fecal samples were collected and analyzed by LC-MS3 based quantitative metaproteomics. Data from mice transplanted with two UC patients were analyzed in this dataset.
2020-11-23 | MSV000086510 | MassIVE
Project description:Here we developed topobiologically complex mini-colons able to undergo tumorigenesis ex vivo by integrating microfabrication, optogenetic, and tissue engineering approaches. With this system, tumorigenic transformation can be spatiotemporally controlled by directing oncogenic activation through blue-light exposure, and emerging colon tumors can be tracked in real-time with single-cell resolution for several weeks without breaking the culture. These induced mini-colons display rich intra- and inter-tumoral diversity and recapitulate key pathophysiological hallmarks displayed by colorectal tumors in vivo. By fine-tuning cell-intrinsic and extrinsic parameters, mini-colons can be leveraged to unveil tumorigenic determinants, including dietary patterns, microbiota-derived metabolites, and pharmacological therapies.
2024-02-24 | GSE221162 | GEO
Project description:Here we developed topobiologically complex mini-colons able to undergo tumorigenesis ex vivo by integrating microfabrication, optogenetic, and tissue engineering approaches. With this system, tumorigenic transformation can be spatiotemporally controlled by directing oncogenic activation through blue-light exposure, and emerging colon tumors can be tracked in real-time with single-cell resolution for several weeks without breaking the culture. These induced mini-colons display rich intra- and inter-tumoral diversity and recapitulate key pathophysiological hallmarks displayed by colorectal tumors in vivo. By fine-tuning cell-intrinsic and extrinsic parameters, mini-colons can be leveraged to unveil tumorigenic determinants, including dietary patterns, microbiota-derived metabolites, and pharmacological therapies.
2024-02-24 | GSE221159 | GEO
Project description:Here we developed topobiologically complex mini-colons able to undergo tumorigenesis ex vivo by integrating microfabrication, optogenetic, and tissue engineering approaches. With this system, tumorigenic transformation can be spatiotemporally controlled by directing oncogenic activation through blue-light exposure, and emerging colon tumors can be tracked in real-time with single-cell resolution for several weeks without breaking the culture. These induced mini-colons display rich intra- and inter-tumoral diversity and recapitulate key pathophysiological hallmarks displayed by colorectal tumors in vivo. By fine-tuning cell-intrinsic and extrinsic parameters, mini-colons can be leveraged to unveil tumorigenic determinants, including dietary patterns, microbiota-derived metabolites, and pharmacological therapies.
2024-02-24 | GSE246568 | GEO
Project description:Primary cilia (PC) are important signaling hubs in cells and we explored their role in colorectal cancer (CRC) and colitis. In the colon we found PC to be mostly present on different subtypes of fibroblasts and exposure of mice to either chemically induced colitis-associated colon carcinogenesis (CAC) or dextran sodium sulfate (DSS)-induced acute colitis decreased PC numbers. We employed conditional knock-out strains for the PC essential genes, Kif3A and Ift88, to generate mice with reduced numbers of PC on colonic fibroblasts. These mice showed an increased susceptibility in the CAC model as well as in DSS-induced colitis. Secretome and immunohistochemical analyses of DSS-treated mice displayed an elevated production of the pro-inflammatory cytokine IL-6 in PC-deficient colons. An inflammatory environment diminished PC presence in primary fibroblast cultures. This was triggered by IL-6 as identified by RNAseq analysis together with blocking experiments, suggesting an activation loop between IL-6 production and PC loss. Notably, an analysis of PC presence on biopsies of patients with ulcerative colitis as well as CRC patients revealed decreased numbers of PC on colonic fibroblasts in pathological versus surrounding normal tissue. Taken together, we provide evidence that a decrease in colonic PC numbers promotes colitis and CRC.
2022-11-29 | PXD033440 | Pride
Project description:Morphine causes microbial dysbiosis. In this study we focused on restoration of native microbiota in morphine treated mice and looked at the extent of restoration and immunological consequences of this restoration. Fecal transplant has been successfully used clinically, especially for treating C. difficile infection2528. With our expanding knowledge of the central role of microbiome in maintenance of host immune homeostasis17, fecal transplant is gaining importance as a therapy for indications resulting from microbial dysbiosis. There is a major difference between fecal transplant being used for the treatment of C. difficile infection and the conditions described in our studies. The former strategy is based on the argument that microbial dysbiosis caused by disproportionate overgrowth of a pathobiont can be out-competed by re-introducing the missing flora by way of a normal microbiome transplant. This strategy is independent of host factors and systemic effects on the microbial composition. Here, we show that microbial dysbiosis caused due to morphine can be reversed by transplantation of microbiota from the placebo-treated animals.
2016-06-01 | E-MTAB-3723 | biostudies-arrayexpress