The intestinal microbiota reprograms intestinal lipid metabolism through long non-coding RNA Snhg9
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE208020 | GEO | 2022/07/15
REPOSITORIES: GEO
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Project description:The intestinal microbiota has been identified as an environmental factor that markedly impacts energy storage and body fat accumulation, yet the underlying mechanisms remain unclear. Here we show that the microbiota regulates body composition through the circadian transcription factor NFIL3. Nfil3 transcription oscillates diurnally in intestinal epithelial cells and the amplitude of the circadian oscillation is controlled by the microbiota through type 3 innate lymphoid cells (ILC3), STAT3, and the epithelial cell circadian clock. NFIL3 controls expression of a circadian lipid metabolic program and regulates lipid absorption and export in intestinal epithelial cells. These findings provide mechanistic insight into how the intestinal microbiota regulates body composition and establish NFIL3 as an essential molecular link among the microbiota, the circadian clock, and host metabolism.
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Project description:Circadian rhythmicity is a defining feature of mammalian metabolism that synchronizes metabolic processes to day-night light cycles. Here, we show that the intestinal microbiota programs diurnal metabolic rhythms in the mouse small intestine through histone deacetylase 3 (HDAC3). The microbiota induced expression of intestinal epithelial HDAC3, which was recruited rhythmically to chromatin and produced synchronized diurnal oscillations in histone acetylation, metabolic gene expression, and nutrient uptake. HDAC3 also functioned non-canonically to coactivate estrogen related receptor a (ERRa), inducing microbiota-dependent rhythmic transcription of the lipid transporter gene Cd36 and promoting lipid absorption and diet-induced obesity. Our findings reveal that HDAC3 integrates microbial and circadian cues to regulate diurnal metabolic rhythms, and pinpoint a key mechanism by which the microbiota controls host metabolism.
2019-09-26 | GSE134303 | GEO
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
Project description:Intestinal lipid metabolism regulates absorption and surface of gut epithelium
| PRJNA638157 | ENA
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
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
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
Project description:Background and aims: Enteroendocrine cells (EECs) and their hormones are essential regulators of whole-body energy homeostasis. EECs sense luminal nutrients and microbial metabolites and subsequently secrete a variety of hormones acting locally or at distance. Impaired development of EECs during embryogenesis is life-threatening in newborn mice and humans due to compromised nutrient absorption. However, the physiological importance of the EEC system in adult mice has not been directedly studied. Herein, we aimed to determine the long-term consequences of a total loss of EECs in healthy adults on energy metabolism, intestinal transcriptome and microbiota. Methods: We depleted intestinal EECs by tamoxifen treatment of adult Neurog3fl/fl; Villin-CreERT2 male mice. We studied intestinal cell differentiation, food efficiency, lipid absorption, microbiota composition, fecal metabolites and transcriptomic responses in the proximal and distal small intestine of mice lacking EECs. We also determined the high-fat diet induced transcriptomic changes in sorted Neurog3eYFP/+EECs. Results: Induction of EECs deficiency in adults is not life-threatening unless fed with a high-fat diet. Under a standard chow diet, mice lose 10% of weight due to impaired food efficiency. Blood concentrations of cholesterol, triglycerides, and free fatty acids are reduced and lipid absorption is impaired and delayed to the distal small intestine. Genes controlling lipogenesis, carbohydrate metabolism and neoglucogenesis are upregulated. Microbiota composition is rapidly altered after ECCs depletion and characterized by decreased -diversity. Bacteroides and Lactobacillus were progressively enriched while Lachnospiraceae declined without impacting fecal short chain fatty acid concentrations. Conclusions: EECs are dispensable for survival in adult male mice under a standard chow diet. The absence of EECs impairs intestinal lipid absorption leading to transcriptomic and metabolic adaptations and remodeling of the gut microbiota.
2023-03-01 | GSE221473 | GEO
Project description:Background and aims: Enteroendocrine cells (EECs) and their hormones are essential regulators of whole-body energy homeostasis. EECs sense luminal nutrients and microbial metabolites and subsequently secrete a variety of hormones acting locally or at distance. Impaired development of EECs during embryogenesis is life-threatening in newborn mice and humans due to compromised nutrient absorption. However, the physiological importance of the EEC system in adult mice has not been directedly studied. Herein, we aimed to determine the long-term consequences of a total loss of EECs in healthy adults on energy metabolism, intestinal transcriptome and microbiota. Methods: We depleted intestinal EECs by tamoxifen treatment of adult Neurog3fl/fl; Villin-CreERT2 male mice. We studied intestinal cell differentiation, food efficiency, lipid absorption, microbiota composition, fecal metabolites and transcriptomic responses in the proximal and distal small intestine of mice lacking EECs. We also determined the high-fat diet induced transcriptomic changes in sorted Neurog3eYFP/+EECs. Results: Induction of EECs deficiency in adults is not life-threatening unless fed with a high-fat diet. Under a standard chow diet, mice lose 10% of weight due to impaired food efficiency. Blood concentrations of cholesterol, triglycerides, and free fatty acids are reduced and lipid absorption is impaired and delayed to the distal small intestine. Genes controlling lipogenesis, carbohydrate metabolism and neoglucogenesis are upregulated. Microbiota composition is rapidly altered after ECCs depletion and characterized by decreased alpha-diversity. Bacteroides and Lactobacillus were progressively enriched while Lachnospiraceae declined without impacting fecal short chain fatty acid concentrations. Conclusions: EECs are dispensable for survival in adult male mice under a standard chow diet. The absence of EECs impairs intestinal lipid absorption leading to transcriptomic and metabolic adaptations and remodeling of the gut microbiota.
2023-03-01 | GSE224026 | GEO
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.
2011-11-23 | GSE33885 | GEO