The gut microbiota downregulates renal MAS1 through H3K9bu in high-fat diet-induced obesity-related hypertensive rats
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE235898 | GEO | 2024/06/27
REPOSITORIES: GEO
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Project description:Gut microbiota has profound effects on obesity and associated metabolic disorders. Targeting and shaping the gut microbiota via dietary intervention using probiotics, prebiotics and synbiotics can be effective in obesity management. Despite the well-known association between gut microbiota and obesity, the microbial alternations by synbiotics intervention, especially at the functional level, are still not characterized. In this study, we investigated the effects of synbiotics on high fat diet (HFD)-induced metabolic disorders, and systematically profiled the microbial profile at both the phylogenetic and functional levels. Synbiotics significantly reversed the HFD-induced change of microbial populations at the levels of richness, taxa and OTUs. Potentially important species Faecalibaculum rodentium and Alistipes putredinis that might mediate the beneficial effects of synbiotics were identified. At the functional level, short chain fatty acid and bile acid profiles revealed that interventions significantly restored cecal levels of acetate, propionate, and butyrate, and synbiotics reduced the elevated total bile acid level. Metaproteomics revealed the effect of synbiotics might be mediated through pathways involved in carbohydrate, amino acid, and energy metabolisms, replication and repair, etc. These results suggested that dietary intervention using our novel synbiotics alleviated HFD-induced weight gain and restored microbial ecosystem homeostasis phylogenetically and functionally.
2022-02-22 | PXD009564 | Pride
Project description:Several aspects common to a Western lifestyle, including obesity and decreased physical activity, are known risks for gastrointestinal cancers. There is an increasing amount of evidence suggesting that diet profoundly affects the composition of the intestinal microbiota. Moreover, there is now unequivocal evidence linking a dysbiotic gut to cancer development. Yet, the mechanisms through which high-fat diet (HFD)-mediated changes in the microbial community impact the severity of tumorigenesis in the gut, remain to be determined. Here we demonstrate that HFD promotes tumor progression in the small intestine of genetically susceptible K-rasG12Dint mice independent of obesity. HFD consumption in conjunction with K-Ras mutation mediates a shift in the composition of gut microbiota, which is associated with a decrease in Paneth cell antimicrobial host defense that compromises dendritic cell (DC) recruitment and MHC-II presentation in the gut-associated lymphoid tissues (GALTs). DC recruitment in GALTs can be normalized, and tumor progression attenuated completely, when K-rasG12Dint mice are supplemented with the short-chain fatty acid butyrate, a bacterial fermentation endproduct. Importantly, Myd88-deficiency completely blocks tumor progression in K-rasG12Dint mice. Transfer of fecal samples from diseased donors into healthy adult K-rasG12Dint mice is sufficient to transmit disease in the absence of HFD. Furthermore, treatment with antibiotics completely blocks HFD-induced tumor progression, suggesting a pivotal role for distinct microbial shifts in aggravating disease in the small intestine. Collectively, these data underscore the importance of the reciprocal interaction between host and environmental factors in selecting intestinal microbiota that favor carcinogenesis, and suggest tumorigenesis may be transmissible among genetically predisposed individuals. 3 mice each for each treatment.
2014-03-28 | E-GEOD-56257 | biostudies-arrayexpress
Project description:Several aspects of a Western lifestyle such as increased obesity and decreased physical activity are associated with increased risk for gastrointestinal cancers1. Although high-fat diet (HFD) induced low-grade inflammation has been closely linked to tumorigenesis2, however, the microbial shift that occurs due to diet and consequent alterations in host immunity have merely been considered to play a critical role during carcinogenesis. Here we show that HFD promotes tumor progression in the small intestine of genetically susceptible mice, however, independently of obesity and diet-induced chronic inflammation. HFD consumption cooperates with mutant K-Ras to mediate a shift in the composition of microbiota, which is associated with a decrease in Paneth cell antimicrobial host defense that compromises dendritic cell (DC) recruitment and MHCII presentation in the gut-associated lymphoid tissues (GALTs). DC recruitment in GALTs can be normalized and tumor progression attenuated completely when K-Ras mutant mice are supplemented with the short chain fatty acid butyrate, a bacterial fermentation end product, or partially when provided with probiotics. Importantly, Myd88-deficiency completely blocks tumor progression in K-ras mutants, however, rather by substantial changes in the microbiota than host-mediated signaling mechanisms. Strikingly, transfer of fecal samples from diseased donors into healthy adult K-ras mutants is sufficient to enhance tumor progression in the absence of HFD suggesting a pivotal role for distinct microbiota shifts in aggravating disease in the small intestine. Collectively, these data underscore the reciprocal interaction between host and environmental factors for the composition of intestinal microbiota that favors carcinogenesis and suggest tumor progression could potentially be “transmitted” in genetically predisposed individuals. 13 samples; S103_396_GroupA_Arkan and S104_429_GroupA_Arkan represent the controls of the first group, S105_394_GroupB_Arkan and S106_429_GroupB_Arkan represent ViRas (mutated) mice of the first group. S982_groupA_ 1 and S983_groupA_2 represent the cotrols of the second group, S984_groupB_3, S985_groupB_4 and S986_groupB_5 represent ViRas (mutant) mice of the second group, S563_CO1979 represent the control of the third group, S564_KO1_1231, S565_KO2_1984 and S566_KO3_2013 represent the ViRas (mutant) mice of the third group. The first group are mice kept on HFD, second group kept on ND and third group kept on HFD plus treated with butyrate
2013-07-01 | E-GEOD-42840 | biostudies-arrayexpress
Project description:Several studies have established a link between high-salt diet, inflammation, and hypertension. Vitamin D supplementation has shown anti-inflammatory effects in many diseases; gut microbiota is also associated with a wide variety of cardiovascular diseases, but potential role of vitamin D and gut microbiota in high-salt diet-induced hypertension remains unclear. Therefore, we used rats with hypertension induced by a high-salt diet as the research object and analyzed the transcriptome of their tissues (kidney and colon) and gut microbiome to conduct an overall analysis of the gut–kidney axis. We aimed to confirm the effects of high salt and calcitriol on the gut–kidney immune system and the composition of the intestinal flora. We demonstrate that consumption of a high-salt diet results in hypertension and inflammation in the colon and kidney and alteration of gut microbiota composition and function. High-salt diet-induced hypertension was found to be associated with seven microbial taxa and mainly associated with reduced production of the protective short-chain fatty acid butyrate. Calcitriol can reduce colon and kidney inflammation, and there are gene expression changes consistent with restored intestinal barrier function. The protective effect of calcitriol may be mediated indirectly by immunological properties. Additionally, the molecular pathways of the gut microbiota-mediated BP regulation may be related to circadian rhythm signals, which needs to be further investigated. An innovative association analysis of the microbiota may be a key strategy to understanding the association between gene patterns and host.
2021-10-12 | GSE184844 | GEO
Project description:Several aspects common to a Western lifestyle, including obesity and decreased physical activity, are known risks for gastrointestinal cancers. There is an increasing amount of evidence suggesting that diet profoundly affects the composition of the intestinal microbiota. Moreover, there is now unequivocal evidence linking a dysbiotic gut to cancer development. Yet, the mechanisms through which high-fat diet (HFD)-mediated changes in the microbial community impact the severity of tumorigenesis in the gut, remain to be determined. Here we demonstrate that HFD promotes tumor progression in the small intestine of genetically susceptible K-rasG12Dint mice independent of obesity. HFD consumption in conjunction with K-Ras mutation mediates a shift in the composition of gut microbiota, which is associated with a decrease in Paneth cell antimicrobial host defense that compromises dendritic cell (DC) recruitment and MHC-II presentation in the gut-associated lymphoid tissues (GALTs). DC recruitment in GALTs can be normalized, and tumor progression attenuated completely, when K-rasG12Dint mice are supplemented with the short-chain fatty acid butyrate, a bacterial fermentation endproduct. Importantly, Myd88-deficiency completely blocks tumor progression in K-rasG12Dint mice. Transfer of fecal samples from diseased donors into healthy adult K-rasG12Dint mice is sufficient to transmit disease in the absence of HFD. Furthermore, treatment with antibiotics completely blocks HFD-induced tumor progression, suggesting a pivotal role for distinct microbial shifts in aggravating disease in the small intestine. Collectively, these data underscore the importance of the reciprocal interaction between host and environmental factors in selecting intestinal microbiota that favor carcinogenesis, and suggest tumorigenesis may be transmissible among genetically predisposed individuals.
2014-03-28 | GSE56257 | GEO
Project description:Background & Aims: In obesity-associated non-alcoholic steatohepatitis (NASH), persistent hepatocellular damage and inflammation are key drivers of fibrosis, the main determinant of NASH-associated mortality. The short chain fatty acid butyrate can exert metabolic improvements and anti-inflammatory activities in NASH. However, its effects on NASH-associated liver fibrosis remains unclear. Methods: Putative antifibrotic effects of butyrate were studied in Ldlr-/-.Leiden mice fed an obesogenic NASH-inducing diet (HFD) containing 2.5% (w/w) butyrate for 38 weeks and compared to an HFD control group. Antifibrotic mechanisms of butyrate were further investigated in TGF-β-stimulated primary human hepatic stellate cells (HSC). Results: HFD-fed mice developed obesity, insulin resistance, increased levels of plasma leptin, adipose tissue inflammation, gut permeability, dysbiosis and NASH-associated fibrosis. Butyrate corrected hyperinsulinemia, lowered plasma leptin levels and attenuated adipose tissue inflammation, without affecting gut permeability or microbiota composition. Butyrate lowered plasma ALT and CK-18M30 and attenuated hepatic steatosis and inflammation. Butyrate inhibited fibrosis development as demonstrated by decreased hepatic collagen content and Sirius-red-positive area. In TGF-β-stimulated HSC, butyrate dose-dependently reduced collagen deposition and decreased procollagen1α1 and PAI-1 protein expression. Transcriptomic analysis and subsequent pathway and upstream regulator analysis revealed deactivation of specific non-canonical TGF-β signaling pathways RhoA/Rock and PI3K/AKT and other important pro-fibrotic regulators (e.g. YAP/TAZ and MYC) by butyrate, providing a potential rationale for its antifibrotic effects. Conclusions: Butyrate protects against the development of obesity and insulin resistance-associated NASH and liver fibrosis. These antifibrotic effects are at least in part attributable to a direct effect on collagen production in hepatic stellate cells, as a result of inhibiting non-canonical TGF-β signaling.
2021-12-21 | GSE179395 | GEO
Project description:Auricularia auricula is a well-known traditional edible and medicinal fungus with high nutritional and pharmacological values, as well as metabolic and immunoregulatory properties. However, the exact mechanisms underlying the effects of Auricularia auricula polysaccharides (AAP) on obesity and related metabolic endpoints, including the role of the gut microbiota, remain insufficiently understood. To determine the mechanistic role of the gut microbiota in observed anti-obesogenic effects AAP, faecal microbiota transplantation (FMT) and pseudo germ-free mice model treated with antibiotics were also applied, together with 16S rRNA genomic-derived taxonomic profiling. HFD murine exposure to AAP thwarted weight-gains, reduced fat depositing, together with upregulating thermogenesis proteomic biomarkers within adipose tissue. These effects were associated with diminished intestine/bloodstream-borne lipid transportation, together with enhanced glucose tolerance. FMT administered in tandem with antibiotic treatment demonstrated the intestinal microbiota was necessary in deploying AAP anti-obesogenic functions. Intestine-dwelling microbial population assessments discovered AAP to enhance (in a selective manner) Papillibacter cinnamivorans, a commensal bacterium having reduced presence within HFD mice. Notably, HFD mice treated with oral formulations of Papillibacter cinnamivorans diminished obesity and was linked to decreased intestinal lipid transportation. Datasets from the present study show that AAP thwarted dietary-driven obesity and metabolism-based disorders through regulating intestinal lipid transportation, a mechanism that is dependent on the gut commensal Papillibacter cinnamivorans. These results indicated AAP and Papillibacter cinnamivorans as newly identified pre- and probiotics that could possibly serve as novel countermeasure against obesity.
2022-05-03 | GSE201951 | GEO
Project description:Auricularia auricula is a well-known traditional edible and medicinal fungus with high nutritional and pharmacological values, as well as metabolic and immunoregulatory properties. However, the exact mechanisms underlying the effects of Auricularia auricula polysaccharides (AAP) on obesity and related metabolic endpoints, including the role of the gut microbiota, remain insufficiently understood. To determine the mechanistic role of the gut microbiota in observed anti-obesogenic effects AAP, faecal microbiota transplantation (FMT) and pseudo germ-free mice model treated with antibiotics were also applied, together with 16S rRNA genomic-derived taxonomic profiling. HFD murine exposure to AAP thwarted weight-gains, reduced fat depositing, together with upregulating thermogenesis proteomic biomarkers within adipose tissue. These effects were associated with diminished intestine/bloodstream-borne lipid transportation, together with enhanced glucose tolerance. FMT administered in tandem with antibiotic treatment demonstrated the intestinal microbiota was necessary in deploying AAP anti-obesogenic functions. Intestine-dwelling microbial population assessments discovered AAP to enhance (in a selective manner) Papillibacter cinnamivorans, a commensal bacterium having reduced presence within HFD mice. Notably, HFD mice treated with oral formulations of Papillibacter cinnamivorans diminished obesity and was linked to decreased intestinal lipid transportation. Datasets from the present study show that AAP thwarted dietary-driven obesity and metabolism-based disorders through regulating intestinal lipid transportation, a mechanism that is dependent on the gut commensal Papillibacter cinnamivorans. These results indicated AAP and Papillibacter cinnamivorans as newly identified pre- and probiotics that could possibly serve as novel countermeasure against obesity.
2022-05-03 | GSE201950 | GEO
Project description:Chronic Kidney Disease (CKD), a global health burden, is strongly associated with age-related renal function decline, hypertension and diabetes, frequent consequences of obesity. Despite extensive studies the mechanisms determining susceptibility to CKD remain elusive. Clinical evidence together with prior studies from our group showed that perinatal metabolic disorders after maternal obesity adversely affect kidney structure and function throughout life. Since obesity and aging processes converge in similar pathways we tested if perinatal obesity induced by High-Fat Diet (HFD)-fed female mice sensitizes aging-associated mechanism in kidneys of newborn mice. Tissue from the kidney cortex and the kidney medulla was collected from offspring of control or HFD-fed mice.
2022-12-31 | E-MTAB-10954 | biostudies-arrayexpress
Project description:Increased evidences demonstrated that gut microbiota targeted diet intervention can alleviate obesity and related metabolic disorders. The underlying mechanism of interactions among diet, microbiota and host still remains unclear. Enterobacter cloacae B29, an endotoxin-producing strain dominated in the gut of a morbidly obese volunteer (weight 174.8 kg, BMI 58.8 kg m-2) was isolated and transplanted to germfree mice. Using deep mRNA sequencing technology, we compared different gene expression profiles in the colon samples of the germfree mice before and after treated with B29 and/or high fat diet (HFD) and identified 279 differential expressed genes in total, including up-regulated genes Apoa4, Ido1, Cyp4a10, and down-regulated genes Cyp2e1, Cyp26b1, Akr1b7, Adipoq, Cyp1a1, Apoa1, Npc1l1, Tff2, Apoc1, Ctla2a, Mttp, Lpl. Fifty-nine GO biological processes and five KEGG pathways, particularly the Peroxisome proliferator-activated receptors (PPARs) signaling pathway, were significantly enriched in response to HFD+B29, which were mainly relevant to inflammation and the metabolism of lipid, lipoprotein and sterols. These functional changes were consistent with the developed obesity, insulin-resistance, and aggravated inflammatory conditions of the HFD+B29 mice. This work provides insight into the gene expression changes in response to HFD+B29, helping to understand the mechanism of the interactions among HFD, B29 and the germfree mice.
2017-02-22 | GSE87027 | GEO