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.

The blood metabolome of cognitive function and brain health in middle-aged adults - influences of genes, gut microbiome, and exposome.

Increasing evidence suggests the involvement of metabolic alterations in neurological disorders, including Alzheimer's disease (AD), and highlights the significance of the peripheral metabolome, influenced by genetic factors and modifiable environmental exposures, for brain health. In this study, we examined 1,387 metabolites in plasma samples from 1,082 dementia-free middle-aged participants of the population-based Rotterdam Study. We assessed the relation of metabolites with general cognition (G-factor) and magnetic resonance imaging (MRI) markers using linear regression and estimated the variance of these metabolites explained by genes, gut microbiome, lifestyle factors, common clinical comorbidities, and medication using gradient boosting decision tree analysis.

Unraveling interindividual variation of trimethylamine -oxide and its precursors at the population level.

Trimethylamine -oxide (TMAO) is a circulating microbiome-derived metabolite implicated in the development of atherosclerosis and cardiovascular disease (CVD). We investigated whether plasma levels of TMAO, its precursors (betaine, carnitine, deoxycarnitine, choline), and TMAO-to-precursor ratios are associated with clinical outcomes, including CVD and mortality. This was followed by an in-depth analysis of their genetic, gut microbial, and dietary determinants.

Early-life stress and the gut microbiome: A comprehensive population-based investigation.

Early-life stress (ELS) has been robustly associated with a range of poor mental and physical health outcomes. Recent studies implicate the gut microbiome in stress-related mental, cardio-metabolic and immune health problems, but research on humans is scarce and thus far often based on small, selected samples, often using retrospective reports of ELS. We examined associations between ELS and the human gut microbiome in a large, population-based study of children.

Association of blood cell-based inflammatory markers with gut microbiota and cancer incidence in the Rotterdam study.

The immune response-gut microbiota interaction is implicated in various human diseases, including cancer. Identifying the link between the gut microbiota and systemic inflammatory markers and their association with cancer will be important for our understanding of cancer etiology. The current study was performed on 8090 participants from the population-based Rotterdam study.

Glaucoma Patients Have a Lower Abundance of Butyrate-Producing Taxa in the Gut.

Purpose: Glaucoma is an eye disease that is the most common cause of irreversible blindness worldwide. It has been suggested that gut microbiota can produce reactive oxygen species and pro-inflammatory cytokines that may travel from the gastric mucosa to distal sites, for example, the optic nerve head or trabecular meshwork. There is evidence for a gut-eye axis, as microbial dysbiosis has been associated with retinal diseases.

Midgut neuroendocrine tumor patients have a depleted gut microbiome with a discriminative signature.

Rationale: When compared to other types of cancer, the prevalence of midgut neuroendocrine tumors (NET) has disproportionally increased over the past decades. To date, there has been very little progress in discovering (epi)genetic drivers and treatment options for these tumors. Recent microbiome research has revealed that enteroendocrine cells communicate with the intestinal microbiome and has provided novel treatment targets for various other cancer types.

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.

Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer's disease.

Alzheimer's disease (AD), the leading cause of dementia, has an estimated heritability of approximately 70%. The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals-16,036 AD cases and 16,522 controls.

Gut microbiota analysis in pediatric-onset multiple sclerosis compared to pediatric monophasic demyelinating syndromes and pediatric controls.

Background And Purpose: Gut microbiota dysbiosis may lead to proinflammatory conditions contributing to multiple sclerosis (MS) etiology. Pediatric-onset MS patients are close to biological disease onset and less exposed to confounders. Therefore, this study investigated gut microbiota composition and functional pathways in pediatric-onset MS, compared to monophasic acquired demyelinating syndromes (mADS) and healthy controls (HCs).

Whole-exome sequencing of 14 389 individuals from the ESP and CHARGE consortia identifies novel rare variation associated with hemostatic factors.

Plasma levels of fibrinogen, coagulation factors VII and VIII and von Willebrand factor (vWF) are four intermediate phenotypes that are heritable and have been associated with the risk of clinical thrombotic events. To identify rare and low-frequency variants associated with these hemostatic factors, we conducted whole-exome sequencing in 10 860 individuals of European ancestry (EA) and 3529 African Americans (AAs) from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium and the National Heart, Lung and Blood Institute's Exome Sequencing Project. Gene-based tests demonstrated significant associations with rare variation (minor allele frequency < 5%) in fibrinogen gamma chain (FGG) (with fibrinogen, P = 9.

The diagnostic value of nasal microbiota and clinical parameters in a multi-parametric prediction model to differentiate bacterial versus viral infections in lower respiratory tract infections.

Background: The ability to accurately distinguish bacterial from viral infection would help clinicians better target antimicrobial therapy during suspected lower respiratory tract infections (LRTI). Although technological developments make it feasible to rapidly generate patient-specific microbiota profiles, evidence is required to show the clinical value of using microbiota data for infection diagnosis. In this study, we investigated whether adding nasal cavity microbiota profiles to readily available clinical information could improve machine learning classifiers to distinguish bacterial from viral infection in patients with LRTI.

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.

Prevalence of and risk factors for extended-spectrum beta-lactamase genes carriership in a population-based cohort of middle-aged and elderly.

Introduction: Increasing resistance to beta-lactam antibiotics is an alarming development worldwide. Fecal carriership of TEM, SHV, CTX-M and CMY was studied in a community-dwelling population of middle-aged and elderly individuals.

Patients And Methods: Feces was obtained from individuals of the Rotterdam Study.

Composition of cutaneous bacterial microbiome in seborrheic dermatitis patients: A cross-sectional study.

Background: Seborrheic dermatitis (SD) is a chronic inflammatory skin disease with a multifactorial aetiology. Malassezia yeasts have been associated with the disease but the role of bacterial composition in SD has not been thoroughly investigated.

Objectives: To profile the bacterial microbiome of SD patients and compare this with the microbiome of individuals with no inflammatory skin disease (controls).

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.