Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Colon gene expression signatures in mice mono-associated with IBD-associated micro-organisms

ABSTRACT: Studying host-microbiota interactions is fundamental to understand mechanisms involved in intestinal inflammation and inflammatory bowel diseases. In this work, we studied these interactions in mice mono-associated with 4 bacteria and 2 yeasts, all representative of intestinal microbiota and/or associated with IBD pathogenesis: Bacteroides thetaiotaomicron, adhesive-invasive Escherichia coli (AIEC), Ruminococcus gnavus, Roseburia intestinalis, Saccharomyces boulardii and Candida albicans. Transcriptomics analyses showed that B. thetaiotaomicron had the highest immunological effect, being able to almost recapitulate the effects of a whole microbiota, and particularly induced Treg pathways. Furthermore, this analysis also pointed out the effects of E. coli AIEC LF82 on IDO activation and of S. boulardii on angiogenesis, as well as major effects of R. gnavus on metabolism. This work therefore reveals information on the role of each micro-organism and proposes several tracks to follow to better understand IBD pathogenesis and identify therapeutic targets 6 mono-associations + 2 controls (germ-free and conventionalized mice), with 5 to 7 mice per group.

ORGANISM(S): Mus musculus

SUBMITTER: Thomas Hoffmann

PROVIDER: E-GEOD-63299 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Microorganisms linked to inflammatory bowel disease-associated dysbiosis differentially impact host physiology in gnotobiotic mice.

Hoffmann Thomas W TW Pham Hang-Phuong HP Bridonneau Chantal C Aubry Camille C Lamas Bruno B Martin-Gallausiaux Camille C Moroldo Marco M Rainteau Dominique D Lapaque Nicolas N Six Adrien A Richard Mathias L ML Fargier Emilie E Le Guern Marie-Emmanuelle ME Langella Philippe P Sokol Harry H

The ISME journal 20150728 2

Studying host-microbiota interactions are fundamental to understanding the mechanisms involved in intestinal homeostasis and inflammation. In this work, we analyzed these interactions in mice that were mono-associated with six microorganisms that are representative of inflammatory bowel disease (IBD)-associated dysbiosis: the bacteria Bacteroides thetaiotaomicron, adhesive-invasive Escherichia coli (AIEC), Ruminococcus gnavus and Roseburia intestinalis; a yeast used as a probiotic drug, Saccharo ...[more]

PMID: 26218241

Similar Datasets

Project description:Epithelial cells of the mammalian intestine are covered with a mucus layer that prevents direct contact with intestinal microbes but also constitutes a substrate for mucus-degrading bacteria. To study the effect of mucus degradation on the host response, germ-free mice were colonized with Akkermansia muciniphila. This anaerobic bacterium belonging to the Verrucomicrobia is specialized in the degradation of mucin, the glycoprotein present in mucus, and found in high numbers in the intestinal tract of human and other mammalian species. Efficient colonization of A. muciniphila was observed with highest numbers in the cecum, where most mucin is produced. In contrast, following colonization by Lactobacillus plantarum, a facultative anaerobe belonging to the Firmicutes that ferments carbohydrates, similar cell-numbers were found at all intestinal sites. Whereas A. muciniphila was located closely associated with the intestinal cells, L. plantarum was exclusively found in the lumen. The global transcriptional host response was determined in intestinal biopsies and revealed a consistent, site-specific, and unique modulation of about 750 genes in mice colonized by A. muciniphila and over 1500 genes after colonization by L. plantarum. Pathway reconstructions showed that colonization by A. muciniphila altered mucosal gene expression profiles toward increased expression of genes involved in immune responses and cell fate determination, while colonization by L. plantarum led to up-regulation of lipid metabolism. These indicate that the colonizers induce host responses that are specific per intestinal location. In conclusion, we propose that A. muciniphila modulates pathways involved in establishing homeostasis for basal metabolism and immune tolerance toward commensal microbiota. Keywords: Analysis of target gene regulation by using microarrays Adult germ-free female NMRI-KI mice (45 – 65 days) were used for bacterial mono-association. Two bacterial strains were used in this study, A. muciniphila MucT (ATTC BAA-835) and L. plantarum WCFS1 (NCIMB 8826). A. muciniphila was grown anaerobically in a basal mucin based medium and L. plantarum was grown anaerobically at 37°C in Man-Rogosa-Sharpe broth (MRS; Le Pont de Claix, France). After 7 days of colonization, mice were killed by cervical dislocation and terminal ileum, cecum and ascending colon specimens were sampled.

Project description:The mammalian gut harbors a diverse microbial community (gut microbiota) that mainly consists of bacteria. Their combined genomes (the microbiome) provide biochemical and metabolic functions that complement host physiology. Maintaining symbiosis seems to be a key requirement for health as dysbiosis is associated with the development of common diseases. Previous studies indicated that the microbiota and the hostM-bM-^@M-^Ys epithelium signal bidirectional inducing transcriptional responses to fine-tune and maintain symbiosis. However, little is known about the hostM-bM-^@M-^Ys responses to the microbiota along the length of the gut as earlier studies of gut microbial ecology mostly used either colonic or fecal samples. This is of importance as not only function and architecture of the gut varies along its length but also microbial distribution and diversity. Few recent studies have begun to investigate microbiota-induced host responses along the length of the gut. However, these reports used whole tissue samples and therefore do not allow drawing conclusions about specificity of the observed responses. Which cells in the intestinal tissue are responsible for the microbially induced response: epithelial, mesenchymal or immune cells? Where are the responding cells located? Furthermore, the gut microbiota has been implicated in epigenetic regulation of the hostM-bM-^@M-^Ys transcriptional profile. We used using extensive microarray analysis of laser capture microdissection (LCM) harvested ileal and colonic tip and crypt fractions from germ-free mice before and during the time course of colonization with a normal microbiota (on days 1, 3, 5 and 7) to investigate the microbiota-induced transcriptional responses and their kinetics in specific and well-defined cell populations of the hostM-bM-^@M-^Ys epithelium. Ileum and colon segments were dissected from germ-free 10-12 weeks old female C57Bl/6 mice and on day 1, 3, 5 and 7 after colonization, washed and frozen as OCT blocks. Cryosections were prepared from these OCT blocks and tip/crypt fractions isolated using laser capture microdissection. To investigate the microbiota-induced transcriptional responses specific for specific subpopulations of intestinal epithelial cells and their kinetics, tip and crypt fractions of ileal and colonic epithelium of germ-free 10-12 weeks old female C57Bl/6 mice before and during the time course of colonization with a normal microbiota (on days 1, 3, 5 and 7) were harvested using laser capture microdissection and probed in an extensive microarray analysis.

Project description:Although microbiota plays a critical role for the normal development and function of host immune systems, the detail of the influence, especially on those in the large intestine (LI), remains unknown. Here, we performed transcriptome analysis using Affymetrix GeneChip on LI of germ-free (GF) and specific pathogen free (SPF) mice of IQI, an inbred strain established from ICR. Experiment Overall Design: Male germ-free (GF) and specific pathogen-free (SPF) IQI/Jic mice were bred and maintained in the laboratory of Central Institute for Experimental Animals (CIEA, Kawasaki, Kanagwa, Japan). GF mice were housed in a Trexler-type flexible film isolator in a standard germ free state and screened on a weekly basis for germ-free status by sampling feces sterilely and culturing on MRS-agar plates under aerobic and anaerobic conditions. All the GF, SPF, ex-GF mice were kept in a 12: 12-h light/dark cycle and at a temperature of 22+-2 ÂºC. Nine week old mice (n=3) were sacrificed by cervical dislocation and the colon was dissected (the colon was not divided into proximal and distal sections and was treated as a single intestinal section). Experiment Overall Design: The SPF mice were provided by the Central Institute for Experimental Animals of Japan. These mice were determined free of the following pathogens (by various techniques including culture, microscopic observation, serological test, and PCR): Dermatophytes, Citrobacter rodentium, Pasteurella pneumotropica, Corynebacterium kutscheri, Pseudomonas aeruginosa, Salmonella spp., Staphylococcus aureus, Mycoplasma pulmonis, Corynebacterium kutscheri, Salmonella typhimurium, Clostridium piliforme, Mycoplasma pulmonis, Mouse hepatitis virus, Sendai virus, Ectromelia virus, Lymphocytic c. virus, Hantavirus, Giardia muris, Spironucleus muris, Syphacia spp., Aspiculuris tetraptera, Ectoparasits, Intestinalprotozoa, Pinworm, Pneumocystis carinii, Helicobacter hepaticus, Helicobacter bilis, EDIM virus(Rotavirus), Pneumonia virus of mice, Minute virus of mice, Mouse adenovirus, Mouse cytomegalovirus, Mouse encephalomyelitis virus, Reovirus type3, and CAR bacillus.

Dataset Information

Colon gene expression signatures in mice mono-associated with IBD-associated micro-organisms

Publications

Microorganisms linked to inflammatory bowel disease-associated dysbiosis differentially impact host physiology in gnotobiotic mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure