Maternal Diet Quality in Pregnancy and Human Milk Extracellular Vesicle and Particle microRNA.

Extracellular vesicle and particle microRNAs (EVP miRNA) in milk have the capacity to facilitate maternal-infant communication in the postpartum period and are hypothesized to play important roles in child development. Maternal diet quality has been linked to milk macronutrient composition, microbiota profiles, as well as various child health outcomes. The aim of this study was to assess the association between maternal diet quality and milk EVP miRNA.

Optimizing Protocols for MicroRNA Profiling of Infant and Toddler Stool.

Background: MicroRNAs (miRNAs) are increasingly being investigated as potential biomarkers for child development and disease. Although a growing number of studies are utilizing infant and toddler stool for transcriptomic analyses, no studies have compared protocols for preserving and extracting miRNAs from this specimen type, despite unique challenges, including abundant levels of RNAses and microbial RNA.

Methods: To address this, we first compared three commercially available kits and four preservation methods for their ability to yield high quality RNA from infant and toddler stool (Phase 1).

Maternal diet quality and circulating extracellular vesicle and particle miRNA during pregnancy.

Purpose: During pregnancy, extracellular vesicle and particle microRNAs (EVP miRNA) in maternal circulation have the capacity to cross the placenta and facilitate maternal-fetal communication. Both dysregulation of circulating EVP miRNA during pregnancy and maternal diet quality have been previously associated with pregnancy complications and adverse birth outcomes. However, little is known about how maternal diet influences circulating EVP miRNA during pregnancy.

Prospective association of the infant gut microbiome with social behaviors in the ECHO consortium.

Background: Identifying modifiable risk factors of autism spectrum disorders (ASDs) may inform interventions to reduce financial burden. The infant/toddler gut microbiome is one such feature that has been associated with social behaviors, but results vary between cohorts. We aimed to identify consistent overall and sex-specific associations between the early-life gut microbiome and autism-related behaviors.

Maternal-Infant Factors in Relation to Extracellular Vesicle and Particle miRNA in Prenatal Plasma and in Postpartum Human Milk.

MicroRNAs (miRNA) in extracellular vesicles and particles (EVPs) in maternal circulation during pregnancy and in human milk postpartum are hypothesized to facilitate maternal-offspring communication via epigenetic regulation. However, factors influencing maternal EVP miRNA profiles during these two critical developmental windows remain largely unknown. In a pilot study of 54 mother-child dyads in the New Hampshire Birth Cohort Study, we profiled 798 EVP miRNAs, using the NanoString nCounter platform, in paired maternal second-trimester plasma and mature (6-week) milk samples.

Metabolomic data presents challenges for epidemiological meta-analysis: a case study of childhood body mass index from the ECHO consortium.

Introduction: Meta-analyses across diverse independent studies provide improved confidence in results. However, within the context of metabolomic epidemiology, meta-analysis investigations are complicated by differences in study design, data acquisition, and other factors that may impact reproducibility.

Objective: The objective of this study was to identify maternal blood metabolites during pregnancy (> 24 gestational weeks) related to offspring body mass index (BMI) at age two years through a meta-analysis framework.

Identifying stationary microbial interaction networks based on irregularly spaced longitudinal 16S rRNA gene sequencing data.

Introduction: The microbial interactions within the human microbiome are complex, and few methods are available to identify these interactions within a longitudinal microbial abundance framework. Existing methods typically impose restrictive constraints, such as requiring long sequences and equal spacing, on the data format which in many cases are violated.

Methods: To identify microbial interaction networks (MINs) with general longitudinal data settings, we propose a stationary Gaussian graphical model (SGGM) based on 16S rRNA gene sequencing data.

Periconceptional and Prenatal Exposure to Metals and Extracellular Vesicle and Particle miRNAs in Human Milk: A Pilot Study.

Human milk is a rich source of microRNAs (miRNAs), which can be transported by extracellular vesicles and particles (EVPs) and are hypothesized to contribute to maternal-offspring communication and child development. Environmental contaminant impacts on EVP miRNAs in human milk are largely unknown. In a pilot study of 54 mother-child pairs from the New Hampshire Birth Cohort Study, we examined relationships between five metals (arsenic, lead, manganese, mercury, and selenium) measured in maternal toenail clippings, reflecting exposures during the periconceptional and prenatal periods, and EVP miRNA levels in human milk.

Machine-learning analysis of cross-study samples according to the gut microbiome in 12 infant cohorts.

There are challenges in merging microbiome data from diverse research groups due to the intricate and multifaceted nature of such data. To address this, we utilized a combination of machine-learning (ML) models to analyze 16S sequencing data from a substantial set of gut microbiome samples, sourced from 12 distinct infant cohorts that were gathered prospectively. Our initial focus was on the mode of delivery due to its prior association with changes in infant gut microbiomes.

Alterations in Microbial-Associated Fecal Metabolites in Relation to Arsenic Exposure Among Infants.

In utero and early life exposure to inorganic arsenic (iAs) alters immune response in experimental animals and is associated with an increased risk of infant infections. iAs exposure is related to differences in the gut microbiota diversity, community structure, and the relative abundance of individual microbial taxa both in laboratory and human studies. Metabolomics permits a direct measure of molecular products of microbial and host metabolic processes.

Umbilical cord blood immune cell profiles in relation to the infant gut microbiome.

During infancy, the interplay between the developing immune system and the microbiome is critical. We examined whether blood immune cell composition at birth in the umbilical cord (inferred by DNA methylation profiling) related to the early infant gut microbiome (assessed by 16S rRNA gene sequencing) among 73 infants in the New Hampshire Birth Cohort Study. We used generalized estimating equations and controlled for false discovery rate to select microbial taxa associated with immune cells.

Associations of maternal plasma and umbilical cord plasma metabolomics profiles with birth anthropometric measures.

Background: The metabolomics profiles of maternal plasma during pregnancy and cord plasma at birth might influence fetal growth and birth anthropometry. The objective was to examine how maternal plasma and umbilical cord plasma metabolites are associated with newborn anthropometric measures, a known predictor of future health outcomes.

Methods: Pregnant women between 24 and 28 weeks of gestation were recruited as part of a prospective cohort study.

The association between early life antibiotic exposure and the gut resistome of young children: a systematic review.

Antimicrobial resistance is a growing public health burden, but little is known about the effects of antibiotic exposure on the gut resistome. As childhood (0-5 years) represents a sensitive window of microbiome development and a time of relatively high antibiotic use, the aims of this systematic review were to evaluate the effects of antibiotic exposure on the gut resistome of young children and identify knowledge gaps. We searched PubMed, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials.

Metagenomic analysis reveals associations between salivary microbiota and body composition in early childhood.

Several studies have shown that body mass index is strongly associated with differences in gut microbiota, but the relationship between body weight and oral microbiota is less clear especially in young children. We aimed to evaluate if there is an association between child growth and the saliva microbiome. We hypothesized that associations between growth and the saliva microbiome would be moderate, similarly to the association between growth and the gut microbiome.

The relationship between the gut microbiome and the risk of respiratory infections among newborns.

Background: Emerging evidence points to a critical role of the developing gut microbiome in immune maturation and infant health; however, prospective studies are lacking.

Methods: We examined the occurrence of infections and associated symptoms during the first year of life in relation to the infant gut microbiome at six weeks of age using bacterial 16S rRNA V4-V5 gene sequencing ( = 465) and shotgun metagenomics ( = 185). We used generalized estimating equations to assess the associations between longitudinal outcomes and 16S alpha diversity and metagenomics species.

MarZIC: A Marginal Mediation Model for Zero-Inflated Compositional Mediators with Applications to Microbiome Data.

Background: The human microbiome can contribute to pathogeneses of many complex diseases by mediating disease-leading causal pathways. However, standard mediation analysis methods are not adequate to analyze the microbiome as a mediator due to the excessive number of zero-valued sequencing reads in the data and that the relative abundances have to sum to one. The two main challenges raised by the zero-inflated data structure are: (a) disentangling the mediation effect induced by the point mass at zero; and (b) identifying the observed zero-valued data points that are not zero (i.

Bronchiolitis hospitalizations in rural New England: clues to disease prevention.

Background: An improved understanding of the clinico-epidemiology of bronchiolitis hospitalizations, a clinical surrogate of respiratory syncytial virus (RSV) disease, is critical to inform public health strategies for mitigating the in-patient burden of bronchiolitis in early life.

Methods: A retrospective chart review was conducted of all bronchiolitis first admissions ( = 295) to the Children's Hospital at Dartmouth-Hitchcock, CHaD, between 1 November 2010 and 31 October 2017 using the relevant International Classification of Diseases (ICD)-9 and ICD-10 codes for this illness. Abstracted data included laboratory confirmation of RSV infection, severity of illness, duration of hospitalization, age at admission in days, weight at admission, prematurity, siblings, and relevant medical pre-existing conditions.

CBEA: Competitive balances for taxonomic enrichment analysis.

Research in human-associated microbiomes often involves the analysis of taxonomic count tables generated via high-throughput sequencing. It is difficult to apply statistical tools as the data is high-dimensional, sparse, and compositional. An approachable way to alleviate high-dimensionality and sparsity is to aggregate variables into pre-defined sets.

Impact of antibiotics on off-target infant gut microbiota and resistance genes in cohort studies.

Background: Young children are frequently exposed to antibiotics, with the potential for collateral consequences to the gut microbiome. The impact of antibiotic exposures to off-target microbes (i.e.

INFORMATION CONTENT OF HIGH-ORDER ASSOCIATIONS OF THE HUMAN GUT MICROBIOTA NETWORK.

The human gastrointestinal tract is an environment that hosts an ecosystem of microorganisms essential to human health. Vital biological processes emerge from fundamental inter- and intra-species molecular interactions that influence the assembly and composition of the gut microbiota ecology. Here we quantify the complexity of the ecological relationships within the human infant gut microbiota ecosystem as a function of the information contained in the nonlinear associations of a sequence of increasingly-specified maximum entropy representations of the system.

Using Satellite Images and Deep Learning to Identify Associations Between County-Level Mortality and Residential Neighborhood Features Proximal to Schools: A Cross-Sectional Study.

What is the relationship between mortality and satellite images as elucidated through the use of Convolutional Neural Networks? Following a century of increase, life expectancy in the United States has stagnated and begun to decline in recent decades. Using satellite images and street view images, prior work has demonstrated associations of the built environment with income, education, access to care, and health factors such as obesity. However, assessment of learned image feature relationships with variation in crude mortality rate across the United States has been lacking.

Chemical exposures assessed via silicone wristbands and endogenous plasma metabolomics during pregnancy.

Background: Metabolomics is a promising method to investigate physiological effects of chemical exposures during pregnancy, with the potential to clarify toxicological mechanisms, suggest sensitive endpoints, and identify novel biomarkers of exposures.

Objective: Investigate the influence of chemical exposures on the maternal plasma metabolome during pregnancy.

Methods: Data were obtained from participants (n = 177) in the New Hampshire Birth Cohort Study, a prospective pregnancy cohort.

Association of Cesarean Delivery and Formula Supplementation with the Stool Metabolome of 6-Week-Old Infants.

Cesarean delivery and formula feeding have both been implicated as important factors associated with perturbations to the infant gut microbiome. To investigate the functional metabolic response of the infant gut microbial milieu to these factors, we profiled the stool metabolomes of 121 infants from a US pregnancy cohort study at approximately 6 weeks of life and evaluated associations with delivery mode and feeding method. Multivariate analysis of six-week stool metabolomic profiles indicated discrimination by both delivery mode and diet.