miRNAome-metabolome wide association study reveals effects of miRNA regulation in eosinophilia and airflow obstruction in childhood asthma.

Background: There are important inter-relationships between miRNAs and metabolites: alterations in miRNA expression can be induced by various metabolic stimuli, and miRNAs play a regulatory role in numerous cellular processes, impacting metabolism. While both specific miRNAs and metabolites have been identified for their role in childhood asthma, there has been no global assessment of the combined effect of miRNAs and the metabolome in childhood asthma.

Methods: We performed miRNAome-metabolome-wide association studies ('miR-metabo-WAS') in two childhood cohorts of asthma to evaluate the contemporaneous and persistent miRNA-metabolite associations: 1) Genetic Epidemiology of Asthma in Costa Rica Study (GACRS) (N = 1121); 2) the Childhood Asthma Management Program (CAMP) (N = 312 and N = 454).

Leveraging DNA methylation to create Epigenetic Biomarker Proxies that inform clinical care: A new framework for Precision Medicine.

The lack of accurate, cost-effective, and clinically relevant biomarkers remains a major barrier to incorporating omic data into clinical practice. Previous studies have shown that DNA methylation algorithms have utility as surrogate measures for selected proteins and metabolites. We expand upon this work by creating DNAm surrogates, termed epigenetic biomarker proxies (EBPs), across clinical laboratories, the metabolome, and the proteome.

Multidimensional Epigenetic Clocks Demonstrate Accelerated Aging Across Physiological Systems in Schizophrenia: A Meta-Analysis.

Importance: Schizophrenia is associated with increased age-related morbidity, mortality, and frailty, which are not entirely explained by behavioral factors. Prior studies using epigenetic clocks have suggested that schizophrenia is associated with accelerated aging, however these studies have primarily used unidimensional clocks that summarize aging as a single "biological age" score.

Objective: This meta-analysis uses multidimensional epigenetic clocks that split aging into multiple scores to analyze biological aging in schizophrenia.

Immunomodulatory metabolites in IgE-mediated food allergy and oral immunotherapy outcomes based on metabolomic profiling.

Background: The immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE-mediated food allergy are unknown.

Objective: To identify novel pathways associated with tolerance in food allergy, we used metabolomic profiling to find pathways important for food allergy in multiethnic cohorts and responses to OIT.

Methods: Untargeted plasma metabolomics data were generated from the VDAART healthy infant cohort (N = 384), a Costa Rican cohort of children with asthma (N = 1040), and a peanut OIT trial (N = 20) evaluating sustained unresponsiveness (SU, protection that lasts after therapy) versus transient desensitization (TD, protection that ends immediately afterward).

High-dimensional Ageome Representations of Biological Aging across Functional Modules.

The aging process involves numerous molecular changes that lead to functional decline and increased disease and mortality risk. While epigenetic aging clocks have shown accuracy in predicting biological age, they typically provide single estimates for the samples and lack mechanistic insights. In this study, we challenge the paradigm that aging can be sufficiently described with a single biological age estimate.

Metabolic phenotypes and vitamin D response in the critically ill: A metabolomic cohort study.

Background & Aims: Although vitamin D deficiency is common in critically ill patients, randomized controlled trials fail to demonstrate benefits of supplementation. We aimed to identify distinct vitamin D responsive metabolic phenotypes prior to trial intervention of high-dose vitamin D by applying machine learning clustering method to metabolomics data from the Correction of Vitamin D Deficiency in Critically Ill Patients (VITdAL-ICU) trial.

Methods: In the randomized, placebo-controlled VITdAL-ICU trial, critically ill adults received placebo or high-dose vitamin D.

Prenatal Fish Oil Supplementation, Maternal COX1 Genotype, and Childhood Atopic Dermatitis: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Eicosanoids have a pathophysiological role in atopic dermatitis (AD), but it is unknown whether this is affected by prenatal ω-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA; ie, fish oil) supplementation and genetic variations in the cyclooxygenase-1 (COX1) pathway.

Objective: To explore the association of n-3 LCPUFA supplementation during pregnancy with risk of childhood AD overall and by maternal COX1 genotype.

Design, Setting, And Participants: This prespecified secondary analysis of a randomized clinical trial included mother-child pairs from the Danish Copenhagen Prospective Studies on Asthma in Childhood 2010 birth cohort, with prospective follow-up until children were aged 10 years.

Pregnancy complications and birth outcomes following low-level exposure to per- and polyfluoroalkyl substances in the vitamin D antenatal asthma reduction trial.

Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic, highly fluorinated aliphatic compounds, commonly utilised in a wide variety of consumer products with diverse applications. Since the genesis of these compounds, a growing body of evidence has demonstrated adverse health effects associated with PFAS exposure. In a racially diverse cohort of 459 pregnant mothers, demographically weighted towards minority representation (black 44.

Bilirubin metabolism in early life and respiratory health during preschool age: A combined analysis of two independent birth cohorts.

Background: Bilirubin has antioxidant properties, and elevated levels within the normal range have been associated with improved lung function and decreased risk of asthma in adults, but studies of young children are scarce. Here, we investigate associations between bilirubin in early life and respiratory health endpoints during preschool age in two independent birth cohorts.

Methods: Bilirubin metabolites were assessed at ages 0.

Urban metabolic and airway immune profiles increase the risk of infections in early childhood.

Background: Infections in childhood remain a leading global cause of child mortality and environmental exposures seem crucial. We investigated whether urbanicity at birth was associated with the risk of infections and explored underlying mechanisms.

Methods: Children (n=633) from the COPSAC mother-child cohort were monitored daily with symptom diaries of infection episodes during the first 3 years and prospectively diagnosed with asthma until age 6 years.

Untargeted metabolomic analysis reveals different metabolites associated with response to mepolizumab and omalizumab in asthma.

Background: There is limited evidence on biomarkers associated with response to the monoclonal antibodies currently approved for asthma treatment. We sought to identify circulatory metabolites associated with response to treatment with mepolizumab or omalizumab.

Methods: We conducted global metabolomic profiling of pre-treatment plasma samples from 100 patients with moderate-to-severe asthma who initiated mepolizumab (n=31) or omalizumab (n=69).

The metabolic role of vitamin D in children's neurodevelopment: a network study.

Neurodevelopmental disorders are rapidly increasing in prevalence and have been linked to various environmental risk factors. Mounting evidence suggests a potential role of vitamin D in child neurodevelopment, though the causal mechanisms remain largely unknown. Here, we investigate how vitamin D deficiency affects children's communication development, particularly in relation to Autism Spectrum Disorder (ASD).

Metabolomics of IgE-Mediated Food Allergy and Oral Immunotherapy Outcomes based on Metabolomic Profiling.

Background: The immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE-mediated food allergy are unknown.

Objective: To identify novel pathways associated with tolerance in food allergy, we used metabolomic profiling to find pathways important for food allergy in multi-ethnic cohorts and responses to OIT.

Methods: Untargeted plasma metabolomics data were generated from the VDAART healthy infant cohort (N=384), a Costa Rican cohort of children with asthma (N=1040), and a peanut OIT trial (N=20) evaluating sustained unresponsiveness (SU, protection that lasts after therapy) versus transient desensitization (TD, protection that ends immediately afterwards).

Network Analysis Reveals Protein Modules Associated with Childhood Respiratory Diseases.

Background: The first year of life is a period of rapid immune development that can impact health trajectories and the risk of developing respiratory-related diseases, such as asthma, recurrent infections, and eczema. However, the biology underlying subsequent disease development remains unknown.

Methods: Using weighted gene correlation network analysis (WGCNA), we derived modules of highly correlated immune-related proteins in plasma samples from children at age 1 year (N=294) from the Vitamin D Antenatal Asthma Reduction Trial (VDAART).

Consistent Multi-Omic Relationships Uncover Molecular Basis of Pediatric Asthma IgE Regulation.

Serum total immunoglobulin E levels (total IgE) capture the state of the immune system in relation to allergic sensitization. High levels are associated with airway obstruction and poor clinical outcomes in pediatric asthma. Inconsistent patient response to anti-IgE therapies motivates discovery of molecular mechanisms underlying serum IgE level differences in children with asthma.

Urinary eicosanoid levels in early life and risk of atopic disease in childhood.

Background: Eicosanoids are lipid mediators including thromboxanes (TXs), prostaglandins (PGs), and leukotrienes with a pathophysiological role in established atopic disease. However, their role in the inception of disease is unclear. This study aimed to investigate the association between urinary eicosanoids in early life and development of atopic disease.