An early-life microbiota metabolite protects against obesity via intestinal PPAR-gamma
Ontology highlight
ABSTRACT:
ORGANISM(S): Mouse Mus Musculus
TISSUE(S): Feces
SUBMITTER: 
Simona Gabriella Codreanu
PROVIDER: ST002186 | MetabolomicsWorkbench | Fri Jun 03 00:00:00 BST 2022
REPOSITORIES: MetabolomicsWorkbench
Similar Datasets
Project description:We studied the effect of dietary fat type, varying in polyunsaturated/saturated fatty acid ratio's (P/S) on development of metabolic syndrome. C57Bl/6J mice were fed purified high-fat diets (45E% fat) containing palm oil (HF-PO; P/S 0.4), olive oil (HF-OO; P/S 1.1) or safflower oil (HF-SO; P/S 7.8) for 8 weeks. A low-fat palm oil diet (LF-PO; 10E% fat) was used as a reference. Additionally, we analyzed diet-induced changes in gut microbiota composition and mucosal gene expression. The HF-PO diet induced a higher body weight gain and liver triglyceride content compared to the HF-OO, HF-SO or LF-PO diet. In the intestine, the HF-PO diet reduced microbial diversity and increased the Firmicutes/Bacteroidetes ratio. Although this fits a typical obesity profile, our data clearly indicate that an overflow of the HF-PO diet to the distal intestine, rather than obesity itself, is the main trigger for these gut microbiota changes. A HF-PO diet-induced elevation of lipid metabolism-related genes in the distal small intestine confirmed the overflow of palm oil to the distal intestine. Some of these lipid metabolism-related genes were previously already associated with the metabolic syndrome. In conclusion, our data indicate that saturated fat (HF-PO) has a more stimulatory effect on weight gain and hepatic lipid accumulation than unsaturated fat (HF-OO and HF-SO). The overflow of fat to the distal intestine on the HF-PO diet induced changes in gut microbiota composition and mucosal gene expression. We speculate that both are directly or indirectly contributive to the saturated fat-induced development of obesity and hepatic steatosis. Keywords: Diet intervention study Nine-week-old C57Bl/6J mice were fed a low-fat diet (LF-PO) and three different types of high-fat diet, based on palm oil (HF-PO; P/S1.0), olive oil (HF-OO; P/S4.6) and safflower oil (HF-SO; P/S10.1) for 8 weeks. Body weight was recorded weekly and after 7 weeks of diet intervention an oral glucose tolerance test was performed. After 2 weeks of diet intervention, 6 mice per high-fat diet group were anaesthetized with a mixture of isofluorane (1.5%), nitrous oxide (70%) and oxygen (30%) and the small intestines were excised. Adhering fat and pancreatic tissue were carefully removed. The small intestines were divided in three equal parts along the proximal to distal axis (SI 1, SI 2 and SI 3) and microarray analysis was performed on mucosal scrapings.
2012-06-17 | E-GEOD-18586 | biostudies-arrayexpress
Project description:Acquisition of the intestinal microbiota begins at birth, and a stable microbial community develops from a succession of key organisms. Disruption of the microbiota during maturation by low-dose antibiotic exposure can alter host metabolism and adiposity. We now show that low-dose penicillin (LDP), delivered from birth, induces metabolic alterations and affects ileal expression of genes involved in immunity. LDP that is limited to early life transiently perturbs the microbiota, which is sufficient to induce sustained effects on body composition, indicating that microbiota interactions in infancy may be critical determinants of long-term host metabolic effects. In addition, LDP enhances the effect of high-fat diet induced obesity. The growth promotion phenotype is transferrable to germ-free hosts by LDP-selected microbiota, showing that the altered microbiota, not antibiotics per se, play a causal role. These studies characterize important variables in early-life microbe-host metabolic interaction and identify several taxa consistently linked with metabolic alterations. C57BL6J mice received low-dose penicillin through their drinking water (6.7 mg/L), control mice did not receive antibiotics. All mice were started on normal chow (13.5% fat kcal). At 17 weeks of age, half of the mice were switched to high fat diet (45% fat kcal). Livers were collected at age 30 weeks, RNA was extracted, and transcriptional differences were measured by microarray analysis.
2014-09-01 | E-GEOD-58086 | biostudies-arrayexpress
Project description:We studied the effect of dietary fat type, varying in polyunsaturated/saturated fatty acid ratio's (P/S) on development of metabolic syndrome. C57Bl/6J mice were fed purified high-fat diets (45E% fat) containing palm oil (HF-PO; P/S 0.4), olive oil (HF-OO; P/S 1.1) or safflower oil (HF-SO; P/S 7.8) for 8 weeks. A low-fat palm oil diet (LF-PO; 10E% fat) was used as a reference. Additionally, we analyzed diet-induced changes in gut microbiota composition and mucosal gene expression. The HF-PO diet induced a higher body weight gain and liver triglyceride content compared to the HF-OO, HF-SO or LF-PO diet. In the intestine, the HF-PO diet reduced microbial diversity and increased the Firmicutes/Bacteroidetes ratio. Although this fits a typical obesity profile, our data clearly indicate that an overflow of the HF-PO diet to the distal intestine, rather than obesity itself, is the main trigger for these gut microbiota changes. A HF-PO diet-induced elevation of lipid metabolism-related genes in the distal small intestine confirmed the overflow of palm oil to the distal intestine. Some of these lipid metabolism-related genes were previously already associated with the metabolic syndrome. In conclusion, our data indicate that saturated fat (HF-PO) has a more stimulatory effect on weight gain and hepatic lipid accumulation than unsaturated fat (HF-OO and HF-SO). The overflow of fat to the distal intestine on the HF-PO diet induced changes in gut microbiota composition and mucosal gene expression. We speculate that both are directly or indirectly contributive to the saturated fat-induced development of obesity and hepatic steatosis. Keywords: Diet intervention study
2012-06-18 | GSE18586 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Acquisition of the intestinal microbiota begins at birth, and a stable microbial community develops from a succession of key organisms. Disruption of the microbiota during maturation by low-dose antibiotic exposure can alter host metabolism and adiposity. We now show that low-dose penicillin (LDP), delivered from birth, induces metabolic alterations and affects ileal expression of genes involved in immunity. LDP that is limited to early life transiently perturbs the microbiota, which is sufficient to induce sustained effects on body composition, indicating that microbiota interactions in infancy may be critical determinants of long-term host metabolic effects. In addition, LDP enhances the effect of high-fat diet induced obesity. The growth promotion phenotype is transferrable to germ-free hosts by LDP-selected microbiota, showing that the altered microbiota, not antibiotics per se, play a causal role. These studies characterize important variables in early-life microbe-host metabolic interaction and identify several taxa consistently linked with metabolic alterations. Refer to individual Series
2014-09-01 | E-GEOD-58087 | biostudies-arrayexpress
Project description:During the last few decades, the long-lasting consequences of nutritional programming during the early phase of life have become increasingly evident, but the effects of maternal nutrition on the developing intestine are currently still relatively underexplored. In this study, we investigated in mice the effects of a maternal Western-style (WS) high fat/cholesterol diet, given during the perinatal period, on gene expression and microbiota composition of two-week-old offspring. Microarray analysis revealed that a perinatal WS diet caused significant changes in gene expression in the small intestine and colon of the suckling offspring. A strong sexually dimorphic effect was observed in the affected genes. However, pathway analysis of the differentially expressed genes displayed that in both sexes metabolic and immune functions were strongly affected. Integration of the microbiota and gene expression data applying a multivariate correlation analyses revealed that Bacteroidaceae, Porphyromonadaceae and Lachnospiraceae were the bacterial families that most strongly correlated with gene expression in the colon and not with the bacterial families displaying the most pronounced change due to perinatal exposure to a WS diet. Amongst the genes demonstrating a strong correlation with one or more bacterial families were genes of key importance for intestinal development or functioning (i.e., Pitx2 and Ace2). In conclusion, our data demonstrate a strong programming effect of a maternal WS diet on the development of the intestine in the offspring. Small intestine and colon were isolated from two-week-old pups of dams fed a low- or Western-style high fat/cholesterol diet and subjected to gene expression profiling.
2016-08-22 | E-GEOD-72705 | biostudies-arrayexpress
Project description:Acquisition of the intestinal microbiota begins at birth, and a stable microbial community develops from a succession of key organisms. Disruption of the microbiota during maturation by low-dose antibiotic exposure can alter host metabolism and adiposity. We now show that low-dose penicillin (LDP), delivered from birth, induces metabolic alterations and affects ileal expression of genes involved in immunity. LDP that is limited to early life transiently perturbs the microbiota, which is sufficient to induce sustained effects on body composition, indicating that microbiota interactions in infancy may be critical determinants of long-term host metabolic effects. In addition, LDP enhances the effect of high-fat diet induced obesity. The growth promotion phenotype is transferrable to germ-free hosts by LDP-selected microbiota, showing that the altered microbiota, not antibiotics per se, play a causal role. These studies characterize important variables in early-life microbe-host metabolic interaction and identify several taxa consistently linked with metabolic alterations. Male mice were exposed to low-dose penicillin (6.7 mg/L), from birth. Ileums were collected at 8 weeks of age, RNA was extracted, and transcriptional differences were measured by microarray analysis.
2014-09-01 | E-GEOD-58085 | 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:Intestinal homeostasis following postnatal microbial colonization requires the coordination of multiple processes, including the activation of immune cells, cell-cell communication, the controlled deposition of extracellular matrix, and epithelial cell turnover and differentiation. The intestine harbors the largest frequency of resident eosinophils of all homeostatic organs, yet the functional significance of eosinophil residence in the gut remains unclear. Eosinophils are equipped to both respond to, and modify, their local tissue environment and thus are able to regulate the adaption of tissues to environmental changes. We report a critical role for eosinophils in regulating villous structure, barrier integrity and motility in the small intestine. Notably, the microbiota was identified as a key driver of small intestinal eosinophil activation and function. Collectively our findings demonstrate a critical role for eosinophils in facilitating mutualistic interactions between host and microbiota and provide a rationale for the functional significance of their early life recruitment in the small intestine.
2023-04-01 | GSE201355 | GEO
Project description:Acquisition of the intestinal microbiota begins at birth, and a stable microbial community develops from a succession of key organisms. Disruption of the microbiota during maturation by low-dose antibiotic exposure can alter host metabolism and adiposity. We now show that low-dose penicillin (LDP), delivered from birth, induces metabolic alterations and affects ileal expression of genes involved in immunity. LDP that is limited to early life transiently perturbs the microbiota, which is sufficient to induce sustained effects on body composition, indicating that microbiota interactions in infancy may be critical determinants of long-term host metabolic effects. In addition, LDP enhances the effect of high-fat diet induced obesity. The growth promotion phenotype is transferrable to germ-free hosts by LDP-selected microbiota, showing that the altered microbiota, not antibiotics per se, play a causal role. These studies characterize important variables in early-life microbe-host metabolic interaction and identify several taxa consistently linked with metabolic alterations. Male and female mice were exposed to low-dose penicillin from birth. In a second experiment, microbiota from female control and LDP mice was transferred to 3-week old female germ-free mice. Livers were collected at 8 weeks of age, RNA was extracted, and transcriptional differences were measured by RNAseq.
2014-09-01 | E-GEOD-58089 | biostudies-arrayexpress