A distinct immunophenotype in children carrying the Blautia enterotype: The generation R study.

Objective: Studies in mouse models and human adults have shown that the intestinal microbiota composition can affect peripheral immune cells. We here examined whether the gut microbiota compositions affect B and T-cell subsets in children.

Methods: The intestinal microbiota was characterized from stool samples of 344 10-year-old children from the Generation R Study by performing 16S rRNA sequencing.

Advanced Glycation End Products (AGEs) in Diet and Skin in Relation to Stool Microbiota: The Rotterdam Study.

Background: Advanced glycation end products (AGEs) are involved in age-related diseases, but the interaction of gut microbiota with dietary AGEs (dAGEs) and tissue AGEs in the population is unknown.

Objective: Our objective was to investigate the association of dietary and tissue AGEs with gut microbiota in the population-based Rotterdam Study, using skin AGEs as a marker for tissue accumulation and stool microbiota as a surrogate for gut microbiota.

Design: Dietary intake of three AGEs (dAGEs), namely carboxymethyl-lysine (CML), -(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MGH1), and carboxyethyl-lysine (CEL), was quantified at baseline from food frequency questionnaires.

Interplay of Metabolome and Gut Microbiome in Individuals With Major Depressive Disorder vs Control Individuals.

Importance: Metabolomics reflect the net effect of genetic and environmental influences and thus provide a comprehensive approach to evaluating the pathogenesis of complex diseases, such as depression.

Objective: To identify the metabolic signatures of major depressive disorder (MDD), elucidate the direction of associations using mendelian randomization, and evaluate the interplay of the human gut microbiome and metabolome in the development of MDD.

Design, Setting And Participants: This cohort study used data from participants in the UK Biobank cohort (n = 500 000; aged 37 to 73 years; recruited from 2006 to 2010) whose blood was profiled for metabolomics.

The gut microbiome and child mental health: A population-based study.

The link between the gut microbiome and the brain has gained increasing scientific and public interest for its potential to explain psychiatric risk. While differences in gut microbiome composition have been associated with several mental health problems, evidence to date has been largely based on animal models and human studies with modest sample sizes. In this cross-sectional study in 1,784 ten-year-old children from the multi-ethnic, population-based Generation R Study, we aimed to characterize associations of the gut microbiome with child mental health problems.

The gut microbiota and depressive symptoms across ethnic groups.

The gut microbiome is thought to play a role in depressive disorders, which makes it an attractive target for interventions. Both the microbiome and depressive symptom levels vary substantially across ethnic groups. Thus, any intervention for depression targeting the microbiome requires understanding of microbiome-depression associations across ethnicities.

Gut microbiome-wide association study of depressive symptoms.

Depression is one of the most poorly understood diseases due to its elusive pathogenesis. There is an urgency to identify molecular and biological mechanisms underlying depression and the gut microbiome is a novel area of interest. Here we investigate the relation of fecal microbiome diversity and composition with depressive symptoms in 1,054 participants from the Rotterdam Study cohort and validate these findings in the Amsterdam HELIUS cohort in 1,539 subjects.

Association of Insulin Resistance and Type 2 Diabetes With Gut Microbial Diversity: A Microbiome-Wide Analysis From Population Studies.

Importance: Previous studies have indicated that gut microbiome may be associated with development of type 2 diabetes. However, these studies are limited by small sample size and insufficient for confounding. Furthermore, which specific taxa play a role in the development of type 2 diabetes remains unclear.

A population-based study on associations of stool microbiota with atopic diseases in school-age children.

Background: Infants with less diverse gut microbiota seem to have higher risks of atopic diseases in early life, but any associations at school age are unclear.

Objectives: This study sought to examine the associations of diversity, relative abundance, and functional pathways of stool microbiota with atopic diseases in school-age children.

Methods: We performed a cross-sectional study within an existing population-based prospective cohort among 1440 children 10 years of age.

Large-scale association analyses identify host factors influencing human gut microbiome composition.

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10) threshold.

Long-term effects of antimicrobial drugs on the composition of the human gut microbiota.

Introduction: Antimicrobial drugs are known to have effects on the human gut microbiota. We studied the long-term temporal relationship between several antimicrobial drug groups and the composition of the human gut microbiota determined in feces samples.

Methods: Feces samples were obtained from a community-dwelling cohort of middle-aged and elderly individuals (Rotterdam Study).

Microbiomics, Metabolomics, Predicted Metagenomics, and Hepatic Steatosis in a Population-Based Study of 1,355 Adults.

Background And Aims: Previous small studies have appraised the gut microbiome (GM) in steatosis, but large-scale studies are lacking. We studied the association of the GM diversity and composition, plasma metabolites, predicted functional metagenomics, and steatosis.

Approach And Results: This is a cross-sectional analysis of the prospective population-based Rotterdam Study.

Diversity, compositional and functional differences between gut microbiota of children and adults.

The gut microbiota has been shown to play diverse roles in human health and disease although the underlying mechanisms have not yet been fully elucidated. Large cohort studies can provide further understanding into inter-individual differences, with more precise characterization of the pathways by which the gut microbiota influences human physiology and disease processes. Here, we aimed to profile the stool microbiome of children and adults from two population-based cohort studies, comprising 2,111 children in the age-range of 9 to 12 years (the Generation R Study) and 1,427 adult individuals in the range of 46 to 88 years of age (the Rotterdam Study).

Integration of epidemiologic, pharmacologic, genetic and gut microbiome data in a drug-metabolite atlas.

Progress in high-throughput metabolic profiling provides unprecedented opportunities to obtain insights into the effects of drugs on human metabolism. The Biobanking BioMolecular Research Infrastructure of the Netherlands has constructed an atlas of drug-metabolite associations for 87 commonly prescribed drugs and 150 clinically relevant plasma-based metabolites assessed by proton nuclear magnetic resonance. The atlas includes a meta-analysis of ten cohorts (18,873 persons) and uncovers 1,071 drug-metabolite associations after evaluation of confounders including co-treatment.

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

Gut 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.

Intestinal microbiome composition and its relation to joint pain and inflammation.

Macrophage-mediated inflammation is thought to have a causal role in osteoarthritis-related pain and severity, and has been suggested to be triggered by endotoxins produced by the gastrointestinal microbiome. Here we investigate the relationship between joint pain and the gastrointestinal microbiome composition, and osteoarthritis-related knee pain in the Rotterdam Study; a large population based cohort study. We show that abundance of Streptococcus species is associated with increased knee pain, which we validate by absolute quantification of Streptococcus species.

Novel taxonomy-independent deep learning microbiome approach allows for accurate classification of different forensically relevant human epithelial materials.

Correct identification of different human epithelial materials such as from skin, saliva and vaginal origin is relevant in forensic casework as it provides crucial information for crime reconstruction. However, the overlap in human cell type composition between these three epithelial materials provides challenges for their differentiation and identification when using previously proposed human cell biomarkers, while their microbiota composition largely differs. By using validated 16S rRNA gene massively parallel sequencing data from the Human Microbiome Project of 1636 skin, oral and vaginal samples, 50 taxonomy-independent deep learning networks were trained to classify these three tissues.

Differences in Systemic IgA Reactivity and Circulating Th Subsets in Healthy Volunteers With Specific Microbiota Enterotypes.

Changes in the intestinal microbiota have been associated with the development of immune-mediated diseases in humans. Additionally, the introduction of defined bacterial species into the mouse intestinal microbiota has been shown to impact on the adaptive immune response. However, how much impact the intestinal microbiota composition actually has on regulating adaptive immunity remains poorly understood.

The effect of antimicrobial drug use on the composition of the genitourinary microbiota in an elderly population.

Background: The urinary tract is inhabited by a diversity of microorganisms, known as the genitourinary microbiota. Here, we investigated the association between the use of antimicrobial drugs and the composition of the genitourinary microbiota.

Results: Clean-catch urinary samples were collected from 27 participants of the Rotterdam Study.

Meta-analysis of human genome-microbiome association studies: the MiBioGen consortium initiative.

Background: In recent years, human microbiota, especially gut microbiota, have emerged as an important yet complex trait influencing human metabolism, immunology, and diseases. Many studies are investigating the forces underlying the observed variation, including the human genetic variants that shape human microbiota. Several preliminary genome-wide association studies (GWAS) have been completed, but more are necessary to achieve a fuller picture.

Microbiome measurement: Possibilities and pitfalls.

Microbiome research is an emerging field in medical sciences. Several studies have made headways in understanding the influence of microbes on our health and disease states. Further progress in mapping microbiome populations across different body sites and understanding the underlying mechanisms of microbiome-host interactions depends critically on study design, collection protocols, analytical genetic techniques, and reference databases.