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Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut

ABSTRACT: This SuperSeries is composed of the following subset Series: GSE23573: B-cell KO mice data GSE23933: human duodenum biopsy data GSE33884: The role of immunoglobulin A GSE33885: The role of transcription factor Gata4 Refer to individual Series

ORGANISM(S): Mus musculus

SUBMITTER: Natalia Shulzhenko

PROVIDER: E-GEOD-23934 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut.

Shulzhenko Natalia N Morgun Andrey A Hsiao William W Battle Michele M Yao Michael M Gavrilova Oksana O Orandle Marlene M Mayer Lloyd L Macpherson Andrew J AJ McCoy Kathy D KD Fraser-Liggett Claire C Matzinger Polly P

Nature medicine 20111120 12

Using a systems biology approach, we discovered and dissected a three-way interaction between the immune system, the intestinal epithelium and the microbiota. We found that, in the absence of B cells, or of IgA, and in the presence of the microbiota, the intestinal epithelium launches its own protective mechanisms, upregulating interferon-inducible immune response pathways and simultaneously repressing Gata4-related metabolic functions. This shift in intestinal function leads to lipid malabsorpt ...[more]

PMID: 22101768

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human duodenum biopsy data

Project description:Using a systems biology approach, we discovered and dissected a three-way interaction between the immune system, the intestinal epithelium, and the microbiota. We found that mice lacking B lymphocytes, or lacking IgA, have low intestinal expression of lipid metabolism genes regulated by the transcription factor GATA4, and a consequent decrease in fat absorption in the intestine. The defect disappeared in germ free mice, suggesting that it is dependent on the microbiota; and sequencing analysis of the bacteria showed subtle differences between normal and B-cell deficient mice. Analysis of gene expression of gut biopsies from patients with common variable immunodeficiency and intestinal dysfunction revealed a high similarity to mouse B-cell knockout profiles. These data provide an explanation for a longstanding enigmatic association between immunodeficiency and defective lipid absorption in humans. this series represents the subsection of the study where we analize gene epxression in duodenum biopsies from CVID patients and contols with unrelated pathologies Reference sample is from normal duodenum (Clontech). Log2 ratio Cy5/Cy3 was used.

2011-11-15 | E-GEOD-23933 | biostudies-arrayexpress

B-cell KO mice data

Project description:Using a systems biology approach, we discovered and dissected a three-way interaction between the immune system, the intestinal epithelium, and the microbiota. We found that mice lacking B lymphocytes, or lacking IgA, have low intestinal expression of lipid metabolism genes regulated by the transcription factor GATA4, and a consequent decrease in fat absorption in the intestine. The defect disappeared in germ free mice, suggesting that it is dependent on the microbiota; and sequencing analysis of the bacteria showed subtle differences between normal and B-cell deficient mice. Analysis of gene expression of gut biopsies from patients with common variable immunodeficiency and intestinal dysfunction revealed a high similarity to mouse B-cell knockout profiles. These data provide an explanation for a longstanding enigmatic association between immunodeficiency and defective lipid absorption in humans. This series represents first part of the study including: 1) B-cell KO mice of different strains and their controls 2) germ free B-cell Ko mice and their controls 3) B lymphocytes Intensity of each channel was extracted from two-color arrays. We used direct dye swap design and performed paired analysis between small intestine of KO and control mice. Corresponding pairs of KO and control were hybridized on the same array and can be matched by the array name. For comparison between B lymphocytes and intestinal tissue we used B-cell KO intestinal samples and B lymphocytes samples balancing the number of Cy5/3 labeled samples in the groups.

2011-11-15 | E-GEOD-23573 | biostudies-arrayexpress

The role of immunoglobulin A

Project description:Using a systems biology approach, we discovered and dissected a three-way interaction between the immune system, the intestinal epithelium, and the microbiota. We found that mice lacking B lymphocytes, or lacking IgA, have low intestinal expression of lipid metabolism genes regulated by the transcription factor GATA4, and a consequent decrease in fat absorption in the intestine. The defect disappeared in germ free mice, suggesting that it is dependent on the microbiota; and sequencing analysis of the bacteria showed subtle differences between normal and B-cell deficient mice. Analysis of gene expression of gut biopsies from patients with common variable immunodeficiency and intestinal dysfunction revealed a high similarity to mouse B-cell knockout profiles. These data provide an explanation for a longstanding enigmatic association between immunodeficiency and defective lipid absorption in humans. This series represents the subsection of the study where we adress the role of immunoglobulin A. The data is from IgA KO and corresponding control mice. Intensity of each channel was extracted from two-color arrays. We used direct dye swap design and performed paired analysis between small intestine of KO and control mice. Corresponding paires of KO and control were hybridized on the same array and can be matched by the array name.

2011-11-23 | E-GEOD-33884 | biostudies-arrayexpress

Disruption of transkingdom communication by antibiotics leads to immune and mitochondrial dysfunction in the gut (main)

Project description:We analyzed the effects of antibiotics using a popular model of gut microbiota depletion in mice by a cocktail of antibiotics. We combined intestinal transcriptome together with metagenomic analysis of the gut microbiota to develop a new bioinformatics approach that probes the links between microbial components and host functions. We found that most antibiotic-induced alterations can be explained by three factors: depletion of the microbiota; direct effects of antibiotics on host tissues; and the effects of remaining antibiotic-resistant microbes. While microbe depletion led to down-regulation of immunity, the two other factors primarily inhibited mitochondrial gene expression and amounts of active mitochondria, and induced cell death. By reconstructing and analyzing a transkingdom network, we discovered that these toxic effects were mediated by virulence/quorum sensing in antibiotic-resistant bacteria. This series includes gene expression in the ileum of control, antibiotics (ABx)-treated, germfree, germfree-ABx-treated and mice colonized with normal or Abx-resistant microbiota. common reference design with a pool of small intestine RNA labeled with Cy3

2015-01-26 | E-GEOD-60566 | biostudies-arrayexpress

Disruption of transkingdom communication by antibiotics leads to immune and mitochondrial dysfunction in the gut

Project description:We analyzed the effects of antibiotics using a popular model of gut microbiota depletion in mice by a cocktail of antibiotics. We combined intestinal transcriptome together with metagenomic analysis of the gut microbiota to develop a new bioinformatics approach that probes the links between microbial components and host functions. We found that most antibiotic-induced alterations can be explained by three factors: depletion of the microbiota; direct effects of antibiotics on host tissues; and the effects of remaining antibiotic-resistant microbes. While microbe depletion led to down-regulation of immunity, the two other factors primarily inhibited mitochondrial gene expression and amounts of active mitochondria, and induced cell death. By reconstructing and analyzing a transkingdom network, we discovered that these toxic effects were mediated by virulence/quorum sensing in antibiotic-resistant bacteria. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-01-26 | E-GEOD-60568 | biostudies-arrayexpress

Disruption of transkingdom communication by antibiotics leads to immune and mitochondrial dysfunction in the gut (LMD)

Project description:We analyzed the effects of antibiotics using a popular model of gut microbiota depletion in mice by a cocktail of antibiotics. We combined intestinal transcriptome together with metagenomic analysis of the gut microbiota to develop a new bioinformatics approach that probes the links between microbial components and host functions. We found that most antibiotic-induced alterations can be explained by three factors: depletion of the microbiota; direct effects of antibiotics on host tissues; and the effects of remaining antibiotic-resistant microbes. While microbe depletion led to down-regulation of immunity, the two other factors primarily inhibited mitochondrial gene expression and amounts of active mitochondria, and induced cell death. By reconstructing and analyzing a transkingdom network, we discovered that these toxic effects were mediated by virulence/quorum sensing in antibiotic-resistant bacteria. This series includes gene expression of the laser microdissected compartments of the ileum such as villous epithelium, lamina propria and crypts from specific pathogen free mice common reference design with a pool of small intestine RNA labeled with Cy3

2015-01-26 | E-GEOD-60567 | biostudies-arrayexpress

Zebrafish toxicogenomics and phenotypic analyses reveal molecular insights into bisphenol-A (BPA) early-life exposure toxicity.

Project description:In this study, developing zebrafish were exposed to 500-4500 Âµg/L BPA for 7 days from 3 hours post-fertilization for a microarray experiment to obtain molecular insights into BPA early-life exposure toxicity. We analyzed a total of 18 arrays; five biological replicate arrays for zebrafish treated with 500 Âµg/L BPA, four biological replicate arrays for zebrafish treated with 1500 Âµg/L BPA, four biological replicate arrays for zebrafish treated with 4500 Âµg/L BPA against 5 biological replicate arrays for control fish. A common reference sample was used for both treated and control samples.

2012-05-31 | E-GEOD-22634 | biostudies-arrayexpress

The role of transcription factor Gata4

Project description:Using a systems biology approach, we discovered and dissected a three-way interaction between the immune system, the intestinal epithelium, and the microbiota. We found that mice lacking B lymphocytes, or lacking IgA, have low intestinal expression of lipid metabolism genes regulated by the transcription factor GATA4, and a consequent decrease in fat absorption in the intestine. The defect disappeared in germ free mice, suggesting that it is dependent on the microbiota; and sequencing analysis of the bacteria showed subtle differences between normal and B-cell deficient mice. Analysis of gene expression of gut biopsies from patients with common variable immunodeficiency and intestinal dysfunction revealed a high similarity to mouse B-cell knockout profiles. These data provide an explanation for a longstanding enigmatic association between immunodeficiency and defective lipid absorption in humans. This series represents the subsection of the study where we address the role of transcription factor Gata4. The data are from conditional KO (Gata4KOvil) and corresponding control mice. Intensity of each channel was extracted from two-color arrays. We used direct dye swap design and performed paired analysis between small intestine of KO and control mice. Corresponding paires of KO and control were hybridized on the same array, except pair X

2011-11-23 | E-GEOD-33885 | biostudies-arrayexpress

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Project description:We have identified eukaryotic translation initiation factor 4E family member 1B (Eif4e1b) as a regulator of maternal RNA translation, whose maternal deletion leads to 2-cell arrest phenotype in mouse embryos. eIF4E1b protein binds mRNA selectively in oocytes and controls their translation in early embryos. eIF4E1b expresses specifically in mouse ovary and we have generated a knock-in mouse line in which HA tag is conjugated to the C terminus of eIF4E1b. We aim to identify eIF4E1b co-factors using mass spectrometry after anit-HA immunoprecipitation (IP) using mouse ovaries.

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