scholarly journals Relationship between gut microbiota and circulating metabolites in population-based cohorts

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Dina Vojinovic ◽  
Djawad Radjabzadeh ◽  
Alexander Kurilshikov ◽  
Najaf Amin ◽  
Cisca Wijmenga ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Multiple Testing ◽  
Ketone Bodies ◽  
Linear Regression Analysis ◽  
Density Lipoprotein ◽  
Population Based ◽  
High Density ◽  
Phase Reaction ◽  
Host Metabolism ◽  
The Impact

AbstractGut microbiota has been implicated in major diseases affecting the human population and has also been linked to triglycerides and high-density lipoprotein levels in the circulation. Recent development in metabolomics allows classifying the lipoprotein particles into more details. Here, we examine the impact of gut microbiota on circulating metabolites measured by Nuclear Magnetic Resonance technology in 2309 individuals from the Rotterdam Study and the LifeLines-DEEP cohort. We assess the relationship between gut microbiota and metabolites by linear regression analysis while adjusting for age, sex, body-mass index, technical covariates, medication use, and multiple testing. We report an association of 32 microbial families and genera with very-low-density and high-density subfractions, serum lipid measures, glycolysis-related metabolites, ketone bodies, amino acids, and acute-phase reaction markers. These observations provide insights into the role of microbiota in host metabolism and support the potential of gut microbiota as a target for therapeutic and preventive interventions.

scholarly journals Relationship between gut microbiota and circulating metabolites in population-based cohorts

2019 ◽  
Author(s):  
Dina Vojinovic ◽  
Djawad Radjabzadeh ◽  
Alexander Kurilshikov ◽  
Najaf Amin ◽  
Cisca Wijmenga ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Multiple Testing ◽  
Linear Regression Analysis ◽  
Density Lipoprotein ◽  
16S Rrna Gene Sequencing ◽  
Population Based ◽  
High Density ◽  
Rrna Gene ◽  
Phase Reaction ◽  
The Impact

ABSTRACTGut microbiota has been implicated in major diseases affecting the human population and has also been linked to triglycerides and high-density lipoprotein levels in the circulation. As recent development in metabolomics allows classifying the lipoprotein particles into more details, we aimed to examine the impact of gut microbiota on circulating metabolites measured by Nuclear Magnetic Resonance (1H-NMR) technology in 2,309 individuals from the Rotterdam Study and the LifeLines-DEEP cohort in whom gut microbiota was profiled using 16S rRNA gene sequencing. The relationship between gut microbiota and metabolites was assessed by linear regression analysis while adjusting for age, sex, body-mass index, technical covariates, medication use, and multiple testing. Our analysis revealed association of 32 microbial families and genera with very-low-density and high-density subfractions, serum lipid measures, glycolysis-related metabolites, amino acids, and acute phase reaction markers. These observations provide novel insights into the role of microbiota in host metabolism and support the potential of gut microbiota as a target for therapeutic and preventive interventions.

Metabolic signatures of genetically elevated vitamin D among Chinese: observational and Mendelian randomization study

2021 ◽  
Author(s):  
Zhenhuang Zhuang ◽  
Canqing Yu ◽  
Yu Guo ◽  
Zheng Bian ◽  
Ling Yang ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Multiple Testing ◽  
Ketone Bodies ◽  
Causal Effect ◽  
Genetic Risk Score ◽  
Density Lipoprotein ◽  
Metabolite Profile ◽  
Population Based ◽  
Causal Association ◽  
Lipoprotein Particle

Abstract Background Observational studies have suggested that higher circulating 25-hydroxyvitamin D [25(OH)D] levels were associated with favorable serum lipids and related metabolites. However, if such observations reflect causality remains unclear. Objective We aimed to investigate the causal effect of elevated 25(OH)D with the detailed systemic metabolite profile in Chinese adults. Methods A total of 225 lipid and other metabolites were quantified in 4,662 individuals in China Kadoorie Biobank. Instrumental variable analyses were performed to test the causal associations of plasma 25(OH)D with the lipids and metabolites. Results Higher plasma 25(OH)D was related to favorable lipid profiles in observational analyses. The genetic risk score was robustly correlated with observed 25(OH)D (beta[SE]= 3.54 [0.32]; P<1×10 -5, F-statistic =122.3) and explained 8.4% of the variation in 25(OH)D in the Chinese population. For all individual metabolites, the causal estimates were not significant for at the threshold P<5×10 -4 (multiple testing corrected). However, the MR estimate showed that per 1-SD increase in genetically determined 25(OH)D was suggestive associated with decreased levels of cholesterol, lipoprotein particle, phospholipids within very small very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) (P≤0.05, nominal significance). For amino acids, fatty acids, ketone bodies, glycoprotein acetyls, fatty acids and other traits, we did not observe any significant causal association. Conclusions The MR analysis of metabolic data based a population-based cohort suggested a potential causal association of plasma 25(OH)D with cholesterol, lipoprotein particle, phospholipids concentrations and total lipids within very small VLDL and IDL. Our findings highlight long-term effect of 25(OH)D levels in maintaining healthy lipid metabolism.

scholarly journals High-Density Lipoproteins and the Kidney

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 764
Author(s):  
Arianna Strazzella ◽  
Alice Ossoli ◽  
Laura Calabresi
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Cholesterol Acyltransferase ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
High Density Lipoproteins ◽  
Lcat Deficiency ◽  
Progression Of Renal Disease ◽  
The Impact

Dyslipidemia is a typical trait of patients with chronic kidney disease (CKD) and it is typically characterized by reduced high-density lipoprotein (HDL)-cholesterol(c) levels. The low HDL-c concentration is the only lipid alteration associated with the progression of renal disease in mild-to-moderate CKD patients. Plasma HDL levels are not only reduced but also characterized by alterations in composition and structure, which are responsible for the loss of atheroprotective functions, like the ability to promote cholesterol efflux from peripheral cells and antioxidant and anti-inflammatory proprieties. The interconnection between HDL and renal function is confirmed by the fact that genetic HDL defects can lead to kidney disease; in fact, mutations in apoA-I, apoE, apoL, and lecithin–cholesterol acyltransferase (LCAT) are associated with the development of renal damage. Genetic LCAT deficiency is the most emblematic case and represents a unique tool to evaluate the impact of alterations in the HDL system on the progression of renal disease. Lipid abnormalities detected in LCAT-deficient carriers mirror the ones observed in CKD patients, which indeed present an acquired LCAT deficiency. In this context, circulating LCAT levels predict CKD progression in individuals at early stages of renal dysfunction and in the general population. This review summarizes the main alterations of HDL in CKD, focusing on the latest update of acquired and genetic LCAT defects associated with the progression of renal disease.

Abstract 260: Knockout of Apolipoprotein A-II Has Dramatic Effects on High-Density Lipoprotein Subspecies Distribution

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Scott M Gordon ◽  
Catherine A Reardon ◽  
Godfrey S Getz ◽  
W S Davidson
Keyword(s):  
Gel Filtration ◽  
Density Lipoprotein ◽  
High Density ◽  
Paraoxonase 1 ◽  
High Density Lipoproteins ◽  
Ionization Mass ◽  
Associated Proteins ◽  
Compositional Diversity ◽  
The Impact ◽  
Modest Effect

High density lipoproteins (HDL) are a highly heterogeneous population of particles composed of various lipids and proteins. They have been demonstrated to possess a diverse variety of functional properties which are thought to contribute to protection against cardiovascular disease (CVD). Proteomics studies have identified up to 75 different proteins which can associate with HDL. The basis for the compositional diversity of HDL is not known but a better understanding will yield important information about its broad functional diversity. To investigate the impact of common HDL apolipoproteins on the distribution of other apolipoproteins, we have begun to systematically fractionate plasma from various HDL apolipoprotein KO mice. Plasma from apoA-I, apoA-IV and apoA-II global KO mice was applied to gel filtration chromatography to distinguish HDL size populations. HDL particles sequestered by a phospholipid binding resin were proteomically analyzed by electrospray ionization mass spectrometry. By comparing elution volume shifts (i.e. particle size variations) for each HDL protein between WT controls and the KO models, we assessed the impact of the deleted protein on HDL size distributions. Ablation of apoA-I, while decreasing total HDL phospholipid by 70%, had a surprisingly small impact on the distribution of the majority of other HDL associated proteins - affecting only 9 of them. Genetic apoA-IV ablation had a similar modest effect shifting a distinct subset of 9 proteins. However, loss of apoA-II, in addition to causing a similar 70% reduction in overall HDL phospholipids, affected the size distribution of some 45 HDL proteins (including several complement proteins and paraoxonase-1). These data suggest that apoA-I, while associated with the majority of HDL phospholipid, may actually interact with relatively few of the lower abundance proteins known to be associated with HDL. ApoA-II on the other hand, may interact with many of these, perhaps acting as a docking site or adaptor molecule.

scholarly journals Serum paraoxonase-1 activity is associated with light to moderate alcohol consumption: the PREVEND cohort study

2018 ◽  
Vol 108 (6) ◽  
pp. 1283-1290 ◽  
Author(s):  
Eke G Gruppen ◽  
Stephan J L Bakker ◽  
Richard W James ◽  
Robin P F Dullaart
Keyword(s):  
Alcohol Consumption ◽  
Linear Regression Analysis ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Sensitivity ◽  
Population Based ◽  
Cross Sectional Study ◽  
Paraoxonase 1 ◽  
Phenyl Acetate ◽  
Cross Sectional

ABSTRACT Background Paraoxonase-1 (PON-1) is a high-density lipoprotein (HDL)-associated enzyme with antioxidative properties, which may protect against the development of cardiovascular disease. Alcohol consumption increases HDL cholesterol, but the extent to which alcohol consumption gives rise to higher serum PON-1 activity is uncertain. Objective In a population-based study, we determined the relation of serum PON-1 activity with alcohol consumption when taking account of HDL cholesterol and apolipoprotein A-I (apoA-I), its major apolipoprotein. Design A cross-sectional study was performed in 8224 participants of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort. Alcohol consumption was categorized as 1) no/rarely (25.3%); 2) 0.1–10 g/d (49.3%); 3) 10–30 g/d (20.1%); and 4) >30 g/d (5.2%) with 1 drink equivalent to 10 g alcohol. Serum PON-1 activity was measured as its arylesterase activity (phenyl acetate as substrate). Results Median serum PON-1 activity was 50.8, 53.1, 54.4, and 55.7 U/L in the 4 categories of alcohol consumption, respectively (P < 0.001). Its increase paralleled the increments in HDL cholesterol and apoA-I. Notably, there was no further increase in PON-1 activity, HDL cholesterol, and apoA-I when alcohol consumption was increased from 10–30 g/d to >30 g/d. Multivariable linear regression analysis demonstrated that PON-1 activity was related to alcohol consumption independently from clinical covariates, high sensitivity C-reactive protein, and lipid concentrations, including HDL cholesterol (P < 0.001 for each category of alcohol consumption with no alcohol consumption as the reference category). Notably, as inferred from standardized β-coefficients, there was no difference in PON-1 activity between 10–30 g alcohol/d and >30 g alcohol/d. Conclusions Alcohol consumption is associated with an increase in serum PON-1 activity, but its effect seems to reach a plateau with alcohol consumption of 10–30 g/d.

Blood Triglyceride and High-Density Lipoprotein Levels Are Associated with Plasma Amyloid-β Transport: A Population-Based Cross-Sectional Study

2021 ◽  
pp. 1-12
Author(s):  
Shan Wei, ◽  
Suhang Shang ◽  
Liangjun Dang ◽  
Fan Gao ◽  
Yao Gao ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Amyloid Β ◽  
Density Lipoprotein ◽  
Underlying Mechanism ◽  
Population Based ◽  
High Density ◽  
Soluble Form ◽  
Cross Sectional ◽  
Low Hdl ◽  
Positive Correlations

Background: Studies have found that blood lipids are associated with plasma amyloid-β (Aβ) levels, but the underlying mechanism is still unclear. Two Aβ transporters, soluble form of low-density lipoprotein receptor related protein-1 (sLRP1) and soluble receptor of advanced glycation end products (sRAGE), are crucial in peripheral Aβ transport. Objective: The aim was to investigate the effects of lipids on the relationships between plasma Aβ and transporter levels. Methods: This study included 1,436 adults aged 40 to 88 years old. Blood Aβ, sLRP1, sRAGE, and lipid levels were measured. Univariate and multivariate analyses were used to analyze the relationships between lipids and plasma Aβ, sLRP1, and sRAGE. Results: After adjusting for all possible covariates, high-density lipoprotein (HDL-c) was positively associated with plasma Aβ 42 and sRAGE (β= 6.158, p = 0.049; β= 121.156, p <  0.001, respectively), while triglyceride (TG) was negatively associated with plasma Aβ 40, Aβ 42, and sRAGE (β= –48.389, p = 0.017; β= –11.142, p = 0.020; β= –147.937, p = 0.003, respectively). Additionally, positive correlations were found between plasma Aβ and sRAGE in the normal TG (Aβ 40: β= 0.034, p = 0.005; Aβ 42: β= 0.010, p = 0.001) and HDL-c groups (Aβ 40: β= 0.023, p = 0.033; Aβ 42: β= 0.008, p = 0.002) but not in the high TG and low HDL-c groups. Conclusion: Abnormal levels of TG and HDL-c are associated with decreased Aβ and sRAGE levels. Positive correlations between plasma Aβ and sRAGE were only found in the normal TG and HDL-c groups but not in the high TG and low HDL-c groups. These results indicated that dyslipidemia contributing to plasma Aβ levels might also be involved in peripheral Aβ clearance.

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