Introduction: Skipping meals is an increasingly common practice to lose weight among North Americ... more Introduction: Skipping meals is an increasingly common practice to lose weight among North American adults of all bodyweights. However, due to a lack of long-term studies, the long-term effect of skipping meals to lose weight on cardiometabolic health outcomes such as a diagnosis of type 2 diabetes mellitus (T2DM) or incident coronary heart disease (CHD) remains unknown, although previous short-term studies of skipping meals and risk factors for T2DM and CHD have suggested plausible biological pathways for a relationship to exist in either direction, protective or harmful. Hypothesis: We assessed the hypotheses that skipping meals to lose weight was associated with long-term risk of incident T2DM and CHD in the Canadian 1995 Nova Scotia Health Survey (NSHS95), and that these associations were influenced by cardiometabolic risk factors. Methods: Skipping meals to lose weight was assessed via questionnaire in a cohort of 2,898 adults in the NSHS95 and was linked to population-based he...
Objectives: To investigate the association between a plant-based diet index and microbial composi... more Objectives: To investigate the association between a plant-based diet index and microbial composition and functionality, as well as the inter-relationships between plant-based diets, gut microbiome...
Background A higher intake of dietary fiber is associated with a decreased risk of chronic inflam... more Background A higher intake of dietary fiber is associated with a decreased risk of chronic inflammatory diseases such as cardiovascular disease and inflammatory bowel disease. This may function in part due to abrogation of chronic systemic inflammation induced by factors such as dysbiotic gut communities. Data regarding the detailed influences of long-term and recent intake of differing dietary fiber sources on the human gut microbiome are lacking. Methods In a cohort of 307 generally healthy men, we examined gut microbiomes, profiled by shotgun metagenomic and metatranscriptomic sequencing, and long-term and recent dietary fiber intake in relation to plasma levels of C-reactive protein (CRP), an established biomarker for chronic inflammation. Data were analyzed using multivariate linear mixed models. Results We found that inflammation-associated gut microbial configurations corresponded with higher CRP levels. A greater intake of dietary fiber was associated with shifts in gut micr...
Background: Macronutrients regulate the gene expression of hepatic nuclear factor 1 alpha (HNF1A)... more Background: Macronutrients regulate the gene expression of hepatic nuclear factor 1 alpha (HNF1A) which plays a key role in in the normal function of pancreatic beta cells and development of insuli...
Background: Trimethylamine N-oxide (TMAO) is proposed as a possible culprit linking red meat inta... more Background: Trimethylamine N-oxide (TMAO) is proposed as a possible culprit linking red meat intake and poor cardiovascular health. The relationship between diet, microbial metabolism, circulating ...
The exposome represents the array of dietary, lifestyle, and demographic factors to which an indi... more The exposome represents the array of dietary, lifestyle, and demographic factors to which an individual is exposed. Individual components of the exposome, or groups of components, are recognized as influencing many aspects of human physiology, including cardiometabolic health. However, the influence of the whole exposome on health outcomes is poorly understood and may differ substantially from the sum of its individual components. As such, studies of the complete exposome are more biologically representative than fragmented models based on subsets of factors. This study aimed to model the system of relationships underlying the way in which the diet, lifestyle, and demographic components of the overall exposome shapes the cardiometabolic risk profile. The current study included 36,496 US Veterans enrolled in the VA Million Veteran Program (MVP) who had complete assessments of their diet, lifestyle, demography, and markers of cardiometabolic health, including serum lipids, blood press...
A lack of prospective studies has been a major barrier for assessing the role of the microbiome i... more A lack of prospective studies has been a major barrier for assessing the role of the microbiome in human health and disease on a population-wide scale. To address this significant knowledge gap, we have launched a large-scale collection targeting fecal and oral microbiome specimens from 20,000 women within the Nurses' Health Study II cohort (the Microbiome Among Nurses study, or Micro-N). Leveraging the rich epidemiologic data that have been repeatedly collected from this cohort since 1989; the established biorepository of archived blood, urine, buccal cell, and tumor tissue specimens; the available genetic and biomarker data; the cohort's ongoing follow-up; and the BIOM-Mass microbiome research platform, Micro-N furnishes unparalleled resources for future prospective studies to interrogate the interplay between host, environmental factors, and the microbiome in human health. These prospectively collected materials will provide much-needed evidence to infer causality in microbiome-associated outcomes, paving the way toward development of microbiota-targeted modulators, preventives, diagnostics and therapeutics. Here, we describe a generalizable, scalable and cost-effective platform used for stool and oral microbiome specimen and metadata collection in the Micro-N study as an example of how prospective studies of the microbiome may be carried out.
Background Healthy plant-based diet index (hPDI) is associated with a lower risk of cardiometabol... more Background Healthy plant-based diet index (hPDI) is associated with a lower risk of cardiometabolic conditions, but its association as well as interactions with microbiome have not been elucidated. Objectives We aimed to investigate the interrelations between hPDI, gut microbiome, and cardiometabolic risk markers. Methods hPDI was derived from dietary assessments by a validated FFQ and was examined in relation to metagenomic profiles of 911 fecal samples collected from 303 men aged 71 ± 4 y with an average BMI (in kg/m2) of 25.2 ± 3.6 in the Men's Lifestyle Validation Study. Principal coordinate (PCo) analysis based on Bray–Curtis dissimilarity was conducted, and interactions between hPDI and PCo were examined by using a metabolic risk score composed of blood lipids, BMI, and glycated hemoglobin. Results After multivariable adjustment, hPDI was significantly associated with the relative abundance of 7 species and 9 pathways. In particular, higher hPDI was significantly associate...
The study aims to determine the shared genetic architecture between COVID-19 severity with existi... more The study aims to determine the shared genetic architecture between COVID-19 severity with existing medical conditions using electronic health record (EHR) data. We conducted a Phenome-Wide Association Study (PheWAS) of genetic variants associated with critical illness (n=35) or hospitalization (n=42) due to severe COVID-19 using genome-wide association summary from the Host Genetics Initiative. PheWAS analysis was performed using genotype-phenotype data from the Veterans Affairs Million Veteran Program (MVP). Phenotypes were defined by International Classification of Diseases (ICD) codes mapped to clinically relevant groups using published PheWAS methods. Among 658,582 Veterans, variants associated with severe COVID-19 were tested for association across 1,559 phenotypes. Variants at the ABO locus (rs495828, rs505922) associated with the largest number of phenotypes (nrs495828= 53 and nrs505922=59); strongest association with venous embolism, odds ratio (ORrs495828 1.33 (p=1.32 × 10...
ObjectivesGut-produced trimethylamine N-oxide (TMAO) is postulated as a possible link between red... more ObjectivesGut-produced trimethylamine N-oxide (TMAO) is postulated as a possible link between red meat intake and poor cardiometabolic health. We investigated whether gut microbiome could modify associations of dietary precursors with TMAO concentrations and cardiometabolic risk markers among free-living individuals.DesignWe collected up to two pairs of faecal samples (n=925) and two blood samples (n=473), 6 months apart, from 307 healthy men in the Men’s Lifestyle Validation Study. Diet was assessed repeatedly using food-frequency questionnaires and diet records. We profiled faecal metagenome and metatranscriptome using shotgun sequencing and identified microbial taxonomic and functional features.ResultsTMAO concentrations were associated with the overall microbial compositions (permutational analysis of variance (PERMANOVA) test p=0.001). Multivariable taxa-wide association analysis identified 10 bacterial species whose abundance was significantly associated with plasma TMAO conce...
Background Adherence to a healthy diet has been associated with reduced risk of chronic diseases.... more Background Adherence to a healthy diet has been associated with reduced risk of chronic diseases. Identifying nutritional biomarkers of diet quality may be complementary to traditional questionnaire-based methods and may provide insights concerning disease mechanisms and prevention. Objective To identify metabolites associated with diet quality assessed via the Alternate Healthy Eating Index (AHEI) and its components. Methods This cross-sectional study used FFQ data and plasma metabolomic profiles, mostly lipid related, from the Nurses’ Health Study (NHS, n = 1460) and Health Professionals Follow-up Study (HPFS, n = 1051). Linear regression models assessed associations of the AHEI and its components with individual metabolites. Canonical correspondence analyses (CCAs) investigated overlapping patterns between AHEI components and metabolites. Principal component analysis (PCA) and explanatory factor analysis were used to consolidate correlated metabolites into uncorrelated factors. W...
Introduction: Skipping meals is an increasingly common practice to lose weight among North Americ... more Introduction: Skipping meals is an increasingly common practice to lose weight among North American adults of all bodyweights. However, due to a lack of long-term studies, the long-term effect of skipping meals to lose weight on cardiometabolic health outcomes such as a diagnosis of type 2 diabetes mellitus (T2DM) or incident coronary heart disease (CHD) remains unknown, although previous short-term studies of skipping meals and risk factors for T2DM and CHD have suggested plausible biological pathways for a relationship to exist in either direction, protective or harmful. Hypothesis: We assessed the hypotheses that skipping meals to lose weight was associated with long-term risk of incident T2DM and CHD in the Canadian 1995 Nova Scotia Health Survey (NSHS95), and that these associations were influenced by cardiometabolic risk factors. Methods: Skipping meals to lose weight was assessed via questionnaire in a cohort of 2,898 adults in the NSHS95 and was linked to population-based he...
Objectives: To investigate the association between a plant-based diet index and microbial composi... more Objectives: To investigate the association between a plant-based diet index and microbial composition and functionality, as well as the inter-relationships between plant-based diets, gut microbiome...
Background A higher intake of dietary fiber is associated with a decreased risk of chronic inflam... more Background A higher intake of dietary fiber is associated with a decreased risk of chronic inflammatory diseases such as cardiovascular disease and inflammatory bowel disease. This may function in part due to abrogation of chronic systemic inflammation induced by factors such as dysbiotic gut communities. Data regarding the detailed influences of long-term and recent intake of differing dietary fiber sources on the human gut microbiome are lacking. Methods In a cohort of 307 generally healthy men, we examined gut microbiomes, profiled by shotgun metagenomic and metatranscriptomic sequencing, and long-term and recent dietary fiber intake in relation to plasma levels of C-reactive protein (CRP), an established biomarker for chronic inflammation. Data were analyzed using multivariate linear mixed models. Results We found that inflammation-associated gut microbial configurations corresponded with higher CRP levels. A greater intake of dietary fiber was associated with shifts in gut micr...
Background: Macronutrients regulate the gene expression of hepatic nuclear factor 1 alpha (HNF1A)... more Background: Macronutrients regulate the gene expression of hepatic nuclear factor 1 alpha (HNF1A) which plays a key role in in the normal function of pancreatic beta cells and development of insuli...
Background: Trimethylamine N-oxide (TMAO) is proposed as a possible culprit linking red meat inta... more Background: Trimethylamine N-oxide (TMAO) is proposed as a possible culprit linking red meat intake and poor cardiovascular health. The relationship between diet, microbial metabolism, circulating ...
The exposome represents the array of dietary, lifestyle, and demographic factors to which an indi... more The exposome represents the array of dietary, lifestyle, and demographic factors to which an individual is exposed. Individual components of the exposome, or groups of components, are recognized as influencing many aspects of human physiology, including cardiometabolic health. However, the influence of the whole exposome on health outcomes is poorly understood and may differ substantially from the sum of its individual components. As such, studies of the complete exposome are more biologically representative than fragmented models based on subsets of factors. This study aimed to model the system of relationships underlying the way in which the diet, lifestyle, and demographic components of the overall exposome shapes the cardiometabolic risk profile. The current study included 36,496 US Veterans enrolled in the VA Million Veteran Program (MVP) who had complete assessments of their diet, lifestyle, demography, and markers of cardiometabolic health, including serum lipids, blood press...
A lack of prospective studies has been a major barrier for assessing the role of the microbiome i... more A lack of prospective studies has been a major barrier for assessing the role of the microbiome in human health and disease on a population-wide scale. To address this significant knowledge gap, we have launched a large-scale collection targeting fecal and oral microbiome specimens from 20,000 women within the Nurses' Health Study II cohort (the Microbiome Among Nurses study, or Micro-N). Leveraging the rich epidemiologic data that have been repeatedly collected from this cohort since 1989; the established biorepository of archived blood, urine, buccal cell, and tumor tissue specimens; the available genetic and biomarker data; the cohort's ongoing follow-up; and the BIOM-Mass microbiome research platform, Micro-N furnishes unparalleled resources for future prospective studies to interrogate the interplay between host, environmental factors, and the microbiome in human health. These prospectively collected materials will provide much-needed evidence to infer causality in microbiome-associated outcomes, paving the way toward development of microbiota-targeted modulators, preventives, diagnostics and therapeutics. Here, we describe a generalizable, scalable and cost-effective platform used for stool and oral microbiome specimen and metadata collection in the Micro-N study as an example of how prospective studies of the microbiome may be carried out.
Background Healthy plant-based diet index (hPDI) is associated with a lower risk of cardiometabol... more Background Healthy plant-based diet index (hPDI) is associated with a lower risk of cardiometabolic conditions, but its association as well as interactions with microbiome have not been elucidated. Objectives We aimed to investigate the interrelations between hPDI, gut microbiome, and cardiometabolic risk markers. Methods hPDI was derived from dietary assessments by a validated FFQ and was examined in relation to metagenomic profiles of 911 fecal samples collected from 303 men aged 71 ± 4 y with an average BMI (in kg/m2) of 25.2 ± 3.6 in the Men's Lifestyle Validation Study. Principal coordinate (PCo) analysis based on Bray–Curtis dissimilarity was conducted, and interactions between hPDI and PCo were examined by using a metabolic risk score composed of blood lipids, BMI, and glycated hemoglobin. Results After multivariable adjustment, hPDI was significantly associated with the relative abundance of 7 species and 9 pathways. In particular, higher hPDI was significantly associate...
The study aims to determine the shared genetic architecture between COVID-19 severity with existi... more The study aims to determine the shared genetic architecture between COVID-19 severity with existing medical conditions using electronic health record (EHR) data. We conducted a Phenome-Wide Association Study (PheWAS) of genetic variants associated with critical illness (n=35) or hospitalization (n=42) due to severe COVID-19 using genome-wide association summary from the Host Genetics Initiative. PheWAS analysis was performed using genotype-phenotype data from the Veterans Affairs Million Veteran Program (MVP). Phenotypes were defined by International Classification of Diseases (ICD) codes mapped to clinically relevant groups using published PheWAS methods. Among 658,582 Veterans, variants associated with severe COVID-19 were tested for association across 1,559 phenotypes. Variants at the ABO locus (rs495828, rs505922) associated with the largest number of phenotypes (nrs495828= 53 and nrs505922=59); strongest association with venous embolism, odds ratio (ORrs495828 1.33 (p=1.32 × 10...
ObjectivesGut-produced trimethylamine N-oxide (TMAO) is postulated as a possible link between red... more ObjectivesGut-produced trimethylamine N-oxide (TMAO) is postulated as a possible link between red meat intake and poor cardiometabolic health. We investigated whether gut microbiome could modify associations of dietary precursors with TMAO concentrations and cardiometabolic risk markers among free-living individuals.DesignWe collected up to two pairs of faecal samples (n=925) and two blood samples (n=473), 6 months apart, from 307 healthy men in the Men’s Lifestyle Validation Study. Diet was assessed repeatedly using food-frequency questionnaires and diet records. We profiled faecal metagenome and metatranscriptome using shotgun sequencing and identified microbial taxonomic and functional features.ResultsTMAO concentrations were associated with the overall microbial compositions (permutational analysis of variance (PERMANOVA) test p=0.001). Multivariable taxa-wide association analysis identified 10 bacterial species whose abundance was significantly associated with plasma TMAO conce...
Background Adherence to a healthy diet has been associated with reduced risk of chronic diseases.... more Background Adherence to a healthy diet has been associated with reduced risk of chronic diseases. Identifying nutritional biomarkers of diet quality may be complementary to traditional questionnaire-based methods and may provide insights concerning disease mechanisms and prevention. Objective To identify metabolites associated with diet quality assessed via the Alternate Healthy Eating Index (AHEI) and its components. Methods This cross-sectional study used FFQ data and plasma metabolomic profiles, mostly lipid related, from the Nurses’ Health Study (NHS, n = 1460) and Health Professionals Follow-up Study (HPFS, n = 1051). Linear regression models assessed associations of the AHEI and its components with individual metabolites. Canonical correspondence analyses (CCAs) investigated overlapping patterns between AHEI components and metabolites. Principal component analysis (PCA) and explanatory factor analysis were used to consolidate correlated metabolites into uncorrelated factors. W...
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