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.
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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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2024-09-02 | BIOMD0000000583 | BioModels
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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.
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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.
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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.
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