Causal relationship between gut microbiota, plasma metabolites, inflammatory cytokines and abdominal aortic aneurysm: a Mendelian randomization study

Clinical and Experimental Hypertension, Год журнала: 2024, Номер 46(1)

Опубликована: Авг. 12, 2024

Background Complex interconnections are evident among gut microbiota, circulating metabolites, inflammatory cytokines, and the pathogenesis of abdominal aortic aneurysms (AAA), with causal dynamics yet to be comprehensively elucidated. The primary objective this study was elucidate potential relationships involving microbiota-mediated plasma AAA.

Язык: Английский

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Causal Relationship between Gut Microbiota, Plasma Metabolites, and Acute Pancreatitis: An Exploratory Mendelian Randomization Study

Опубликована: Янв. 1, 2025

Background: Emerging evidence suggests a significant correlation between pancreatitis and gut microbiota, yet the causal relationship underlying mechanism remain largely undetermined. Given that microbiota plays crucial role in regulating circulating metabolites, we aimed to elucidate how these interactions impact risk of acute (AP).Methods: Using two-sample Mendelian randomization (MR) analysis, investigated links among plasma AP. Enrichment analysis was performed determine primary metabolite classes metabolic pathways associated with AP risk.Findings: The MR revealed 18 microbial taxa 59 metabolites effects on Furthermore, mediation identified seven as potential intermediaries pathway from AP, emphasizing critical carbohydrate metabolism via polyol fructolysis, well lipid homeostasis, disease's pathogenesis.Interpretation: Our systematic study provided comprehensive characterization causally novel mediating microbiota's effect risk. These findings provide new insights into microbiome-related signatures influencing suggest targets for future research intervention.Funding: This supported by Shandong Provincial Natural Science Foundation (Grant/Award Number: ZR2019PH070) Taishan Scholars Program Province China tsqn202306374).Declaration Interest: authors declare no competing interests.Ethical Approval: Ethical approval informed consent participants were acquired each cohort enrolled original GWAS studies, accordance their local regulations institute requirements. All this study, based summary-level data publicly available databases, require further ethical permit.

Язык: Английский

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A prediction study on the occurrence risk of heart disease in older hypertensive patients based on machine learning

BMC Geriatrics, Год журнала: 2025, Номер 25(1)

Опубликована: Янв. 11, 2025

Constructing a predictive model for the occurrence of heart disease in elderly hypertensive individuals, aiming to provide early risk identification. A total 934 participants aged 60 and above from China Health Retirement Longitudinal Study with 7-year follow-up (2011-2018) were included. Machine learning methods (logistic regression, XGBoost, DNN) employed build predicting patients. Model performance was comprehensively assessed using discrimination, calibration, clinical decision curves. After older patients, 243 individuals (26.03%) developed disease. Older patients baseline comorbid dyslipidemia, chronic pulmonary diseases, arthritis or rheumatic diseases faced higher future Feature selection significantly improved compared original variable set. The ROC-AUC logistic DNN 0.60 (95% CI: 0.53-0.68), 0.64 0.57-0.71), 0.67 0.60-0.73), respectively, regression achieving optimal calibration. XGBoost demonstrated most noticeable benefit as threshold increased. effectively identifies based on data CHARLS cohort. results suggest that have developing This information could facilitate identification

Язык: Английский

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The association of lipids and novel non-statin lipid-lowering drug target with osteoporosis: evidence from genetic correlations and Mendelian randomization

BMC Musculoskeletal Disorders, Год журнала: 2025, Номер 26(1)

Опубликована: Фев. 1, 2025

It remains controversial whether lipids affect osteoporosis (OP) or bone mineral density (BMD), and causality has not been established. This study aimed to investigate the genetic associations between lipids, novel non-statin lipid-lowering drug target genes, OP BMD. Mendelian randomization (MR) method was used explore 179 lipid species OP, Drug-target MR analysis causal angiopoietin-like protein 3 (ANGPTL3) apolipoprotein C3 (APOC3) inhibitors on The IVW results with Bonferroni correction indicated that triglyceride (TG) (51:3) (OR = 1.0029; 95% CI: 1.0014–1.0045; P 0.0002) TG (56:6) 1.0021; 1.0008–1.0033; 0.0011) were associated an increased risk of OP; (51:2) 0.9543; 0.9148–0.9954; 0.0298) decreased BMD; ANGPTL3 inhibitor 1.1342; 1.0393–1.2290; 0.0093) APOC3 1.0506; 1.0155–1.0857; 0.0058) genetically predicted TGs showed have potential serve as targets treat prevent OP.

Язык: Английский

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TCF7L2 as a target of peripheral artery disease in patients with type 2 diabetes: A 2-sample Mendelian randomization and bioinformatics study

Medicine, Год журнала: 2025, Номер 104(7), С. e41431 - e41431

Опубликована: Фев. 14, 2025

This study examines the causal relationship between type 2 diabetes (T2D) and peripheral artery disease (PAD) their potential mechanisms based on analysis of Gene Expression Omnibus database 2-sample Mendelian randomization (MR). The first part involved a MR comprehensive meta-analysis. Differences in results were assessed using inverse-variance weighting. Heterogeneity was examined Cochrane Q statistical test. leave-one-out method applied for sensitivity analysis. horizontal pleiotropic effect MR-Egger intercept technique. second differential gene weighted coexpression network Subsequently, we overlapped consolidated from parts to identify key genes them. suggested statistically significant correlation incidence PAD T2D (odds ratio: 1.22, 95% confidence interval: 1.13–1.32, P = 3.74e−07). We anticipated pivotal role TCF7L2 T2D. significantly associated with risk. Simultaneously, deepened our understanding underlying both diseases, proposing as promising target.

Язык: Английский

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The effects of ursodeoxycholic acid on cardiometabolic risk factors: a systematic review and meta-analysis of randomized controlled trials

BMC Cardiovascular Disorders, Год журнала: 2025, Номер 25(1)

Опубликована: Фев. 21, 2025

Язык: Английский

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Sex Differences in Atrial Fibrillation: Evidence from Circulating Metabolites

Metabolites, Год журнала: 2025, Номер 15(3), С. 170 - 170

Опубликована: Март 2, 2025

Background: Significant sex differences exist in atrial fibrillation (AF). Better understanding of its underlying mechanism would help AF management. This study aimed to investigate the contribution circulating metabolites and association between them. Methods: A total 108 patients with were enrolled. Untargeted metabolomics performed plasma samples male female patients. Correlation analysis clinical characteristics Mendelian randomization used identify sex-specific associated AF, which was further validated additional Transcriptomics data left atrium molecular alteration responding identified metabolites. The effect selected on cardiomyocytes investigated. Results: 60 annotated found different levels Among these metabolites, three 7-Methylguanosine, succinic acid, N-Undecylbenzenesulfonic positively related remodeling. Additionally, acid significantly increased risk (OR = 1.26; 95% CI: 1.13 1.40; p < 0.001). And, SUCLA2, gene metabolism, (fold change 1.53; 0.008). Treatment led cardiomyocyte hypertrophy mitochondrial dysfunction. Conclusions: highlights identifies associations AF. is much higher patients, contributes process

Язык: Английский

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Data-driven pathway level analysis of metabolomics data in the Estonian Biobank associates carbon metabolism with incident hypertension

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 7, 2025

Purpose: The purpose of this study was to find metabolic changes associated with incident hypertension in the volunteer-based Estonian Biobank. Methods: We used a subcohort Biobank where metabolite levels had been measured by mass-spectrometry (LC-MS, Metabolon platform). divided annotated metabolites 989 individuals into KEGG pathways, followed principal component analysis each pathway, resulting dataset 91 pathway components. Next, we defined cases and controls based on electronic health records, 101 450 controls. Cox proportional hazards models replicated results separate cohort Biobank, assayed LC-MS Broad platform including 582 individuals. Results: Our show that body mass index carbon metabolism are both discovery replication cohorts. Conclusion: demonstrate high-dimensional can be meaningfully reduced informative components subsequently analysed an interpretable way, metabolomics from different platform.

Язык: Английский

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Pathway level metabolomics analysis identifies carbon metabolism as a key factor of incident hypertension in the Estonian Biobank

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 12, 2025

Abstract The purpose of this study was to find metabolic changes associated with incident hypertension in the volunteer-based Estonian Biobank. We used a subcohort Biobank where metabolite levels had been measured by mass-spectrometry (LC-MS, Metabolon platform). divided annotated metabolites 989 individuals into KEGG pathways, followed principal component analysis each pathway, resulting dataset 91 pathway components. Next, we defined cases and controls based on electronic health records, 101 450 controls. Cox proportional hazards models replicated results separate cohort Biobank, assayed LC-MS Broad platform including 582 individuals. Our show that body mass index carbon metabolism are both discovery replication cohorts. demonstrate high-dimensional can be meaningfully reduced informative components subsequently analysed an interpretable way, metabolomics from different platform.

Язык: Английский

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Association Between Multiple Plasma Toxic Metal and Metalloid Exposures and Hypertension in Elderly Chinese Adults

Biological Trace Element Research, Год журнала: 2025, Номер unknown

Опубликована: Март 21, 2025

Язык: Английский

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