scholarly journals Environmental factors dominate over host genetics in shaping human gut microbiota composition

2017 ◽  
Author(s):  
Daphna Rothschild ◽  
Omer Weissbrod ◽  
Elad Barkan ◽  
Tal Korem ◽  
David Zeevi ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Human Genetics ◽  
Human Microbiome ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Nucleotide Polymorphisms ◽  
Human Gut ◽  
Extrinsic Factors ◽  
Host Genetics ◽  
Microbiome Composition

AbstractHuman gut microbiome composition is shaped by multiple host intrinsic and extrinsic factors, but the relative contribution of host genetic compared to environmental factors remains elusive. Here, we genotyped a cohort of 696 healthy individuals from several distinct ancestral origins and a relatively common environment, and demonstrate that there is no statistically significant association between microbiome composition and ethnicity, single nucleotide polymorphisms (SNPs), or overall genetic similarity, and that only 5 of 211 (2.4%) previously reported microbiome-SNP associations replicate in our cohort. In contrast, we find similarities in the microbiome composition of genetically unrelated individuals who share a household. We define the termbiome-explainabilityas the variance of a host phenotype explained by the microbiome after accounting for the contribution of human genetics. Consistent with our finding that microbiome and host genetics are largely independent, we find significant biome-explainability levels of 16-33% for body mass index (BMI), fasting glucose, high-density lipoprotein (HDL) cholesterol, waist circumference, waist-hip ratio (WHR), and lactose consumption. We further show that several human phenotypes can be predicted substantially more accurately when adding microbiome data to host genetics data, and that the contribution of both data sources to prediction accuracy is largely additive. Overall, our results suggest that human microbiome composition is dominated by environmental factors rather than by host genetics.

scholarly journals The Effect of Haplotypes in the CETP and LIPC Genes on the Triglycerides to HDL-C Ratio and Its Components in the Roma and Hungarian General Populations

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 56 ◽  
Author(s):  
Peter Piko ◽  
Szilvia Fiatal ◽  
Nardos Abebe Werissa ◽  
Bayu Begashaw Bekele ◽  
Gabor Racz ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Odds Ratio ◽  
Hepatic Lipase ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Roma Population ◽  
Transfer Protein ◽  
General Populations

Background: The triglycerides (TG) to high-density lipoprotein (HDL)-cholesterol (HDL-C) ratio (TG/HDL-C) is a well-known predictor for cardiovascular diseases (CVDs) with great heritability background. The cholesteryl ester transfer protein (CETP) and hepatic lipase (LIPC) gene affect TG/HDL-C ratio. This study aims to explore the association between haplotypes (H) in CETP (based on 5 single nucleotide polymorphisms (SNPs)) and LIPC (based on 6 SNPs) genes and the TG/HDL-C ratio and its components, among Roma and Hungarian general populations. Methods: The prevalence of haplotypes and their effect on HDL-C, TG and TG/HDL-C ratio were calculated in both populations and compared. Results: Ten haplotypes in CETP and 6 in LIPC gene were identified. Three haplotypes in CETP and 3 in LIPC have significant effect on HDL-C level, whereas two in CETP and 3 in LIPC on TG level. The H6 in CETP (β = 0.52, p = 0.015; odds ratio (OR) = 1.87, p = 0.009) and H5 in LIPC (β = 0.56, p < 0.001; OR = 1.51, p = 0.002) have a significant increasing effect on TG/HDL-C ratio and have shown higher prevalence among the Roma, as compared to Hungarian general population. The H2 in the CETP gene has a decreasing effect on the TG/HDL-C ratio (OR = 0.58, p = 0.019) and is significantly less frequent among the Roma. Conclusions: Accumulation of harmful haplotypes in CETP and LIPC genes might have a role in the elevated TG/HDL-C ratio in the Roma population, which contributes to a higher risk in the development of cardiovascular diseases.

scholarly journals The Human Salivary Microbiome Is Shaped by Shared Environment Rather than Genetics: Evidence from a Large Family of Closely Related Individuals

mBio ◽  
2017 ◽  
Vol 8 (5) ◽  
Author(s):  
Liam Shaw ◽  
Andre L. R. Ribeiro ◽  
Adam P. Levine ◽  
Nikolas Pontikos ◽  
Francois Balloux ◽  
...  
Keyword(s):  
Genetic Similarity ◽  
Genetic Relatedness ◽  
Dominant Factor ◽  
Shared Environment ◽  
Ashkenazi Jewish ◽  
Nucleotide Polymorphisms ◽  
Host Genetics ◽  
Microbiome Composition ◽  
Genome Wide ◽  
Host Genetic

ABSTRACT The human microbiome is affected by multiple factors, including the environment and host genetics. In this study, we analyzed the salivary microbiomes of an extended family of Ashkenazi Jewish individuals living in several cities and investigated associations with both shared household and host genetic similarities. We found that environmental effects dominated over genetic effects. While there was weak evidence of geographical structuring at the level of cities, we observed a large and significant effect of shared household on microbiome composition, supporting the role of the immediate shared environment in dictating the presence or absence of taxa. This effect was also seen when including adults who had grown up in the same household but moved out prior to the time of sampling, suggesting that the establishment of the salivary microbiome earlier in life may affect its long-term composition. We found weak associations between host genetic relatedness and microbiome dissimilarity when using family pedigrees as proxies for genetic similarity. However, this association disappeared when using more-accurate measures of kinship based on genome-wide genetic markers, indicating that the environment rather than host genetics is the dominant factor affecting the composition of the salivary microbiome in closely related individuals. Our results support the concept that there is a consistent core microbiome conserved across global scales but that small-scale effects due to a shared living environment significantly affect microbial community composition. IMPORTANCE Previous research shows that the salivary microbiomes of relatives are more similar than those of nonrelatives, but it remains difficult to distinguish the effects of relatedness and shared household environment. Furthermore, pedigree measures may not accurately measure host genetic similarity. In this study, we include genetic relatedness based on genome-wide single nucleotide polymorphisms (SNPs) (rather than pedigree measures) and shared environment in the same analysis. We quantify the relative importance of these factors by studying the salivary microbiomes in members of a large extended Ashkenazi Jewish family living in different locations. We find that host genetics plays no significant role and that the dominant factor is the shared environment at the household level. We also find that this effect appears to persist in individuals who have moved out of the parental household, suggesting that aspects of salivary microbiome composition established during upbringing can persist over a time scale of years. IMPORTANCE Previous research shows that the salivary microbiomes of relatives are more similar than those of nonrelatives, but it remains difficult to distinguish the effects of relatedness and shared household environment. Furthermore, pedigree measures may not accurately measure host genetic similarity. In this study, we include genetic relatedness based on genome-wide single nucleotide polymorphisms (SNPs) (rather than pedigree measures) and shared environment in the same analysis. We quantify the relative importance of these factors by studying the salivary microbiomes in members of a large extended Ashkenazi Jewish family living in different locations. We find that host genetics plays no significant role and that the dominant factor is the shared environment at the household level. We also find that this effect appears to persist in individuals who have moved out of the parental household, suggesting that aspects of salivary microbiome composition established during upbringing can persist over a time scale of years.

scholarly journals Ultra-rapid metagenotyping of the human gut microbiome

2020 ◽  
Author(s):  
Zhou Jason Shi ◽  
Boris Dimitrov ◽  
Chunyu Zhao ◽  
Stephen Nayfach ◽  
Katherine S. Pollard
Keyword(s):  
Population Structure ◽  
High Performance ◽  
Human Microbiome ◽  
Metagenomic Sequencing ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Human Gut ◽  
Single Nucleotide ◽  
Sequencing Errors ◽  
Global Population

AbstractSequence variation is used to quantify population structure and identify genetic determinants of phenotypes that vary within species. In the human microbiome and other environments, single nucleotide polymorphisms (SNPs) are frequently detected by aligning metagenomic sequencing reads to catalogs of genes or genomes. But this requires high-performance computing and enough read coverage to distinguish SNPs from sequencing errors. We solved these problems by developing the GenoTyper for Prokaytotes (GT-Pro), a suite of novel methods to catalog SNPs from genomes and use exact k-mer matches to perform ultra-fast reference-based SNP calling from metagenomes. Compared to read alignment, GT-Pro is more accurate and two orders of magnitude faster. We discovered 104 million SNPs in 909 human gut species, characterized their global population structure, and tracked pathogenic strains. GT-Pro democratizes strain-level microbiome analysis by making it possible to genotype hundreds of metagenomes on a personal computer.Software availabilityGT-Pro is available at https://github.com/zjshi/gt-pro.

scholarly journals Alcohol Drinking, Apolipoprotein Polymorphisms and the Risk of Cardiovascular Diseases

2021 ◽  
Vol 18 ◽  
Author(s):  
Flavio Maria Ceci ◽  
Mauro Ceccanti ◽  
Carla Petrella ◽  
Mario Vitali ◽  
Marisa Patrizia Messina ◽  
...  
Keyword(s):  
Risk Factor ◽  
Alcohol Drinking ◽  
Protective Factor ◽  
Heavy Drinking ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Protective Role ◽  
Nucleotide Polymorphisms ◽  
Moderate Drinking ◽  
Apolipoprotein E4

: Lipoprotein disorders are a major risk factor for atherosclerotic neuro-cardiovascular disease (ACVD) and are heavily influenced by lifestyle, including alcohol drinking. Moderate drinkers have a lower ACVD risk than abstainers because of their higher levels of high-density lipoprotein (HDL) cholesterol, an important protective factor against ACVD. On the contrary, heavy drinking increases ACVD risk. According to a large literature body, ethanol intoxication modifies lipid serum profile and induces endothelial dysfunction. Single nucleotide polymorphisms may influence the relationship between alcohol drinking, HDL cholesterol level, and atherosclerotic risk. The risk of ACVD in heavy drinkers seems enhanced in patients with apolipoprotein E4 allele, interleukin-6-174 polymorphism, and cholesteryl ester transfer protein TaqIB polymorphism. Apolipoprotein E4 is a known risk factor for ACVD, while apolipoprotein E2 has mixed effects. Therefore, even if a "protective role" may be attributed to moderate drinking, this effect cannot be extended to everyone.

Understanding the development of the gut microbiome in pigs: an overview

2022 ◽  
pp. 179-202
Author(s):  
Marion Borey ◽  
◽  
Jordi Estelle ◽  
Claire Rogel-Gaillard ◽  
◽  
...  
Keyword(s):  
Environmental Factors ◽  
Microbial Communities ◽  
Gut Microbiome ◽  
Environmental Changes ◽  
Feed Additives ◽  
Fecal Microbiome ◽  
Host Genetics ◽  
Microbiome Composition ◽  
Living Organisms ◽  
Host Development

Living organisms continuously and intimately interact with commensal microbial communities referred to as microbiota and microbiomes. These complex ecosystems provide their hosts with vital services. The gut microbiome develops and diversifies after birth in pigs, as in all mammals. The diversification dynamics follows the host development early in life, reaches an initial level of richness and stabilization before 60 days of age, and continues to mature but at a much lower rate while ageing and adapting to environmental changes. There is a wide variation in microbiome composition at individual and group levels, due to a combination of many factors including host genetics, environmental factors, feed and feed additives, and farm practices. Although the gut microbiome displays region-specific composition along the digestive tract, with likely sequential, complementary biological functionalities, the fecal microbiome is often considered as a good surrogate and provides many of the associations identified with host phenotypes.

scholarly journals CETP genotypes and HDL-cholesterol phenotypes in the HERITAGE Family Study

2007 ◽  
Vol 31 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Nadine Spielmann ◽  
Arthur S. Leon ◽  
D. C. Rao ◽  
Treva Rice ◽  
James S. Skinner ◽  
...  
Keyword(s):  
Endurance Training ◽  
White Women ◽  
Family Study ◽  
Apoe Genotype ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Nucleotide Polymorphisms ◽  
Beneficial Effects ◽  
Before And After ◽  
Apoe Genotypes

Associations between cholesteryl ester transfer protein (CETP) polymorphisms and high-density lipoprotein cholesterol (HDL-c) levels before and after 20 wk of endurance training were investigated in the HERITAGE Family Study. Plasma HDL-c, HDL2-c, HDL3-c, and apolipoprotein (apo)A1 levels were measured, and 13 CETP single nucleotide polymorphisms (SNPs) were genotyped in 265 blacks and 486 whites. Three haplotypes defined by SNPs at the −1337, −971, and −629 sites were strongly associated with baseline HDL-c levels in whites. Both C−1337T and C−629A were associated with baseline HDL-c ( P < 0.001) and apoA1 ( P < 0.01) when tested separately. However, only C−629A remained significant in a combined model. G−971A was not associated with HDL phenotypes, but showed significant interactions with C−629A ( P = 0.002) on baseline traits. Genotype-by-sex interactions were observed at the −629 locus for HDL3-c ( P = 0.004) and apoA1 ( P = 0.02) training responses in whites. In women, the −629 A/A homozygotes showed greater increases in HDL3-c ( P = 0.02) and apoA1 ( P = 0.02) levels than the other genotypes. Finally, apolipoprotein E (APOE) genotype and the CETP C−629A locus contributed independently and in additive fashion to the HDL traits, explaining 6.0–8.8% of the variance. The CETP −1337T and −629A alleles are associated with higher baseline HDL-c and apoA1 levels. The beneficial effects of endurance training on plasma HDL3-c and apoA1 levels are evident in white women homozygous for the −629A allele. The CETP and APOE genotypes account for up to 9% of the variance in HDL-c phenotypes in the HERITAGE Family Study.

scholarly journals Host genetics exerts lifelong effects upon hindgut microbiota and its association with bovine growth and immunity

2021 ◽  
Author(s):  
Peixin Fan ◽  
Corwin D. Nelson ◽  
J. Danny Driver ◽  
Mauricio A. Elzo ◽  
Francisco Peñagaricano ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Environmental Changes ◽  
Short Chain Fatty Acids ◽  
Growth Stages ◽  
Intestinal Epithelial ◽  
Nucleotide Polymorphisms ◽  
Extrinsic Factors ◽  
Host Genetics ◽  
Genetic Components ◽  
Microbiota Structure

AbstractThe gut microbiota is a complex ecological community that plays multiple critical roles within a host. Known intrinsic and extrinsic factors affect gut microbiota structure, but the influence of host genetics is understudied. To investigate the role of host genetics upon the gut microbiota structure, we performed a longitudinal study in which we evaluated the hindgut microbiota and its association with animal growth and immunity across life. We evaluated three different growth stages in an Angus-Brahman multibreed population with a graduated spectrum of genetic variation, raised under variable environmental conditions and diets. We found the gut microbiota structure was changed significantly during growth when preweaning, and fattening calves experienced large variations in diet and environmental changes. However, regardless of the growth stage, we found gut microbiota is significantly influenced by breed composition throughout life. Host genetics explained the relative abundances of 52.2%, 40.0%, and 37.3% of core bacterial taxa at the genus level in preweaning, postweaning, and fattening calves, respectively. Sutterella, Oscillospira, and Roseburia were consistently associated with breed composition at these three growth stages. Especially, butyrate-producing bacteria, Roseburia and Oscillospira, were associated with nine single-nucleotide polymorphisms (SNPs) located in genes involved in the regulation of host immunity and metabolism in the hindgut. Furthermore, minor allele frequency analysis found breed-associated SNPs in the short-chain fatty acids (SCFAs) receptor genes that promote anti-inflammation and enhance intestinal epithelial barrier functions. Our findings provide evidence of dynamic and lifelong host genetic effects upon gut microbiota, regardless of growth stages. We propose that diet, environmental changes, and genetic components may explain observed variation in critical hindgut microbiota throughout life.

scholarly journals A comprehensive assessment of demographic, environmental, and host genetic associations with gut microbiome diversity in healthy individuals

Microbiome ◽  
2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Petar Scepanovic ◽  
◽  
Flavia Hodel ◽  
Stanislas Mondot ◽  
Valentin Partula ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Gut Microbiome ◽  
Genetic Factors ◽  
European Ancestry ◽  
Nucleotide Polymorphisms ◽  
Healthy Individuals ◽  
Fecal Microbiome ◽  
Microbiome Composition ◽  
Microbiome Diversity ◽  
Host Genetic

Abstract Background The gut microbiome is an important determinant of human health. Its composition has been shown to be influenced by multiple environmental factors and likely by host genetic variation. In the framework of the Milieu Intérieur Consortium, a total of 1000 healthy individuals of western European ancestry, with a 1:1 sex ratio and evenly stratified across five decades of life (age 20–69), were recruited. We generated 16S ribosomal RNA profiles from stool samples for 858 participants. We investigated genetic and non-genetic factors that contribute to individual differences in fecal microbiome composition. Results Among 110 demographic, clinical, and environmental factors, 11 were identified as significantly correlated with α-diversity, ß-diversity, or abundance of specific microbial communities in multivariable models. Age and blood alanine aminotransferase levels showed the strongest associations with microbiome diversity. In total, all non-genetic factors explained 16.4% of the variance. We then searched for associations between > 5 million single nucleotide polymorphisms and the same indicators of fecal microbiome diversity, including the significant non-genetic factors as covariates. No genome-wide significant associations were identified after correction for multiple testing. A small fraction of previously reported associations between human genetic variants and specific taxa could be replicated in our cohort, while no replication was observed for any of the diversity metrics. Conclusion In a well-characterized cohort of healthy individuals, we identified several non-genetic variables associated with fecal microbiome diversity. In contrast, host genetics only had a negligible influence. Demographic and environmental factors are thus the main contributors to fecal microbiome composition in healthy individuals. Trial registration ClinicalTrials.gov identifier NCT01699893

scholarly journals Gut microbiome transition across a lifestyle gradient in Himalaya

2018 ◽  
Author(s):  
Aashish R Jha ◽  
Emily R Davenport ◽  
Yoshina Gautam ◽  
Dinesh Bhandari ◽  
Sarmila Tandukar ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Gut Microbiome ◽  
Alpha Diversity ◽  
Water Source ◽  
Drinking Water Source ◽  
Human Gut ◽  
Bacterial Composition ◽  
Microbiome Composition ◽  
The World

The composition of the gut microbiome in industrialized populations differs from those living traditional lifestyles. However, it has been difficult to separate the contributions of human genetic and geographic factors from lifestyle/modernization. Here, we characterize the stool bacterial composition of four Himalayan populations to investigate how the gut community changes in response to shifts in human lifestyles. These groups led seminomadic hunting-gathering lifestyles until transitioning to varying dependence upon farming. The Tharu began farming 250-300 years ago, the Raute and Raji transitioned 30-40 years ago, and the Chepang retain many aspects of a foraging lifestyle. We assess the contributions of dietary and environmental factors on their gut microbiota and find that the gut microbiome composition is significantly associated with lifestyle. The Chepang foragers harbor elevated abundance of taxa associated with foragers around the world. Conversely, the gut microbiomes of populations that have transitioned to farming are more similar to those of Americans, with agricultural dependence and several associated lifestyle and environmental factors correlating with the extent of microbiome divergence from the foraging population. For example, our results show that drinking water source and solid cooking fuel are significantly associated with the gut microbiome. Despite the pronounced differences in gut bacterial composition across populations, we found little differences in alpha diversity across populations. These findings in genetically similar populations living in the same geographical region establish the key role of lifestyle in determining human gut microbiome composition and point to the next challenging steps of isolating dietary effects from other factors that change during modernization.

HDL and clinical and biochemical correlates in Italian non-smoker women

2004 ◽  
Vol 42 (12) ◽  
Author(s):  
Federico Bigazzi ◽  
Beatrice Dal Pino ◽  
Francesco Forastiere ◽  
Riccardo Pistelli ◽  
Giuseppe Rossi ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Environmental Factors ◽  
Apolipoprotein E ◽  
Total Cholesterol ◽  
Plasma Levels ◽  
Apolipoprotein B ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Female Population ◽  
Apolipoprotein A

AbstractHigh-density lipoprotein (HDL)-cholesterol levels, inversely related to the risk of myocardial infarction, are determined by genetic and environmental factors. The aim of this study was to evaluate the prevalence of low and high HDL plasma levels and the influence of environmental factors and lipid profile in an Italian non-smoker female population. HDL, apolipoprotein A-I, apolipoproteins, lipids and estrogen plasma levels were measured in a population of 1471 women with a mean age of 45±14years. HDL values ≤35mg/dl were noted in 11.2% of the subjects, showing 2.4% coronary heart disease (CHD) prevalence. The 90th percentile was characterized by HDL levels ≥66mg/dl and the absence of coronary atherosclerosis. Total cholesterol, apolipoprotein B and triglycerides (r=−0.31, p<0.0001) were the main determinants of HDL levels; apolipoprotein E, estrogen use, body mass index (BMI), alcohol consumption and age showed a weaker correlation. Apolipoprotein A-I concentration was influenced more notably by estrogen use, total cholesterol and apolipoprotein E; levels of triglycerides, apolipoprotein B, BMI, age and alcohol consumption are less important. The parameters considered here, taken together, explain HDL and apolipoprotein A-I variability of approximately 31% and 24%, respectively. A surprisingly high prevalence of very low (≤35mg/dl) and high (≥66mg/dl) HDL levels in Italian women further confirms the importance of studies on the HDL distribution in different population groups.

Sign in / Sign up

Export Citation Format

Share Document