Administration of a bacterial lysate to the airway compartment is sufficient to inhibit allergen-induced lung eosinophilia in germ-free mice.

The nexus between eosinophils and microbes is attracting increasing attention. We previously showed that airway administration of sterile microbial products contained in dust collected from traditional dairy farms virtually abrogated bronchoalveolar lavage (BAL) eosinophilia and other cardinal asthma phenotypes in allergen-sensitized specific pathogen-free (SPF) mice. Interestingly, comparable inhibition of allergen-induced BAL eosinophilia and promotion of airway barrier integrity were found upon administration of a sterile, pharmacological-grade bacterial lysate, OM-85, to the airway compartment of allergen-sensitized SPF mice.

Maternal prenatal immunity, neonatal trained immunity, and early airway microbiota shape childhood asthma development.

Background: The path to childhood asthma is thought to initiate in utero and be further promoted by postnatal exposures. However, the underlying mechanisms remain underexplored. We hypothesized that prenatal maternal immune dysfunction associated with increased childhood asthma risk (revealed by low IFN-γ:IL-13 secretion during the third trimester of pregnancy) alters neonatal immune training through epigenetic mechanisms and promotes early-life airway colonization by asthmagenic microbiota.

The OM-85 bacterial lysate inhibits SARS-CoV-2 infection of epithelial cells by downregulating SARS-CoV-2 receptor expression.

Background: Treatments for coronavirus disease 2019, which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are urgently needed but remain limited. SARS-CoV-2 infects cells through interactions of its spike (S) protein with angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) on host cells. Multiple cells and organs are targeted, particularly airway epithelial cells.

Airway administration of OM-85, a bacterial lysate, blocks experimental asthma by targeting dendritic cells and the epithelium/IL-33/ILC2 axis.

Background: Microbial interventions against allergic asthma have robust epidemiologic underpinnings and the potential to recalibrate disease-inducing immune responses. Oral administration of OM-85, a standardized lysate of human airways bacteria, is widely used empirically to prevent respiratory infections and a clinical trial is testing its ability to prevent asthma in high-risk children. We previously showed that intranasal administration of microbial products from farm environments abrogates experimental allergic asthma.

Maternal Cytokine Profiles during Pregnancy Predict Asthma in Children of Mothers without Asthma.

Little is known about whether maternal immune status during pregnancy influences asthma development in the child. We measured cytokine production in supernatants from mitogen-stimulated peripheral blood immune cells collected during and after pregnancy from the mothers of children enrolled in the Tucson Infant Immune Study, a nonselected birth cohort. Physician-diagnosed active asthma in children through age 9 and a history of asthma in their mothers were assessed through questionnaires.

Of pleiotropy and trajectories: Does the TGF-β pathway link childhood asthma and chronic obstructive pulmonary disease?

The study of developmental trajectories is where epigenetics truly shines. The "epi" in epigenetics captures the fact that although epigenetic processes also preside over the maintenance and termination of gene expression, the unfolding and remodeling of chromatin architecture are especially critical to prepare genes for regulated transcription. These properties imply being on a path, a trajectory to events that will occur later thanks to epigenetic programming.

The neonatal methylome as a gatekeeper in the trajectory to childhood asthma.

Asthma is a heterogeneous group of conditions that typically begin in early life and result in recurrent, reversible bronchial obstruction. The role played by epigenetic mechanisms in the pathogenesis of childhood asthma is understood only in part. Here we discuss asthma epigenetics within a developmental perspective based on our recent demonstration that the epigenetic trajectory to childhood asthma begins at birth.

Epigenome-wide analysis links SMAD3 methylation at birth to asthma in children of asthmatic mothers.

Background: The timing and mechanisms of asthma inception remain imprecisely defined. Although epigenetic mechanisms likely contribute to asthma pathogenesis, little is known about their role in asthma inception.

Objective: We sought to assess whether the trajectory to asthma begins already at birth and whether epigenetic mechanisms, specifically DNA methylation, contribute to asthma inception.

Epigenetic Mechanisms in Asthma.

Asthma and allergic diseases are among the most prevalent chronic noncommunicable diseases of childhood, but the underlying pathogenetic mechanisms are poorly understood. Because epigenetic mechanisms link gene regulation to environmental cues and developmental trajectories, their contribution to asthma and allergy pathogenesis is under active investigation. DNA methylation signatures associated with concurrent disease and with the development of asthma during childhood asthma have been identified, but their significance is not easily interpretable.

Epigenetics in allergic diseases.

Purpose Of Review: Allergic diseases are among the most prevalent chronic diseases of childhood, affecting more than 7 million children in the United States. Epidemiological evidence supports the idea that the inception of allergic diseases is typically before the preschool years, even when chronic symptoms do not emerge until adulthood. The role of epigenetic mechanisms (particularly DNA methylation) in allergic disease is under active investigation because these mechanisms are known to be at the interface of gene regulation, environmental stimuli, and developmental processes, all of which are essential for the pathogenesis for asthma and allergy.

Early predictors of asthma and allergy in children: the role of epigenetics.

Purpose Of Review: Asthma and allergic diseases are among the most prevalent chronic noncommunicable diseases of childhood. Although epidemiologic studies suggest that asthma begins in the preschool years, the lack of firm diagnostic criteria to distinguish children who will wheeze only transiently during early-life lower respiratory illnesses from children who will wheeze persistently and develop asthma prevents pinpointing the time at which disease truly begins. Epigenetic mechanisms link gene regulation to environmental cues and developmental trajectories.

Epigenetics of human asthma and allergy: promises to keep.

Objective: The interest in asthma epigenetics is high because epigenetic mechanisms likely contribute to the environmental origins of the disease and its phenotypic variability. This review presents the main findings of asthma epigenetics and the challenges that still delay progress.

Data Sources: We examined the current literature on asthma epigenetics (31 reviews and 25 original data publications).