Maternal microbiome regulation prevents early allergic airway diseases in mouse offspring

Abstract

Background: Asthma is a serious global health problem, severely affecting the lives of sufferers and their families. An exceptionally hygienic home and reduced microbial exposure can aggravate the incidence of childhood asthma. Methods: Specific-pathogen-free BALB/c mice were pre-treated with bacterial lysate (BL; 1 mg/kg) as a high microbial load maternal mouse model, and then, the offspring mice were established as an allergic airway disease (AAD) model. The expression levels of TLR2, TLR4, and HDAC9 in the mother's intestine and the offspring's lungs were detected. Relevant indicators of regulatory T cells (Tregs) were identified in the mother and offspring mice. The changes in the expression of Th1-, Th2-, Th9-, and Th17-related cytokines in the offspring mice were evaluated among different pretreated groups. Results: After augmenting the mothers' intestinal microbiota through oral BL gavage, the expression of TLR2 and TLR4 in the colon mucosa and colon lymphoid tissues was enhanced and that of HDAC9 in the colon mucosa was decreased, and the proportion of spleen Tregs was increased. The offspring showed similar changes in the AAD model compared with the offspring of the control-group mothers: TLR2 and TLR4 expression in the lungs and the proportion of spleen Tregs increased, HDAC9 expression in the lungs decreased, and AAD-induced airway pathologic characteristics were reversed; additionally, Th1/Th2 and Th9 imbalances were rectified. Conclusions: This study presents a new framework for the prevention of childhood asthma, elucidating the mechanism of regulating the mother's intestinal microbiome to protect the offspring's early asthma via animal experiments.

Identification of Biomarkers and Pathogenesis in Severe Asthma by Co-expression Network Analysis

“…That means TLR2 may induce remission of asthma [35]. Another study in mouse also suggested appropriate stimulation of the TLR2/4 pathway may help to prevent asthma later in life [36]. Thus, further studies are needed to reveal the effect of TLR2 on asthma and disease severity.…”

From gut to placenta: understanding how the maternal microbiome models life-long conditions

“…Since the primary source of microorganisms that will colonize and shape the microbiota of the newborn comes from the maternal origin, it is worth asking whether there is a connection between dysbiosis of the maternal microbiota and the development of diseases in adulthood, such as metabolic and cardiovascular diseases, neurodevelopment alterations or changes in the immune system. Supplementary Table 1 shows different studies describing this relationship (10).…”

“…In contrast, the control progeny showed elevated IL-4 and IL-5 concentrations and GATA3 expression. An essential element recognized in the mothers of the intervention group was the decrease in histone deacetylase 9 expression, suggesting possible epigenetic mechanisms by which the microbiota reduces the risk of developing allergic diseases (10).…”

“…There is substantial controversy regarding the presence of microorganisms in prenatal intrauterine locations and the consequent environment of sterility in which the fetus develops: the traditional dogma that the human fetal environment is sterile and that the neonate microbiome is acquired during and after birth (4)(5)(6)(7)(8)(9)(10)(11) stands against the evidence supporting that the healthy human placenta harbors a unique low-biomass microbiome composed of nonpathogenic commensal microbiota (12)(13)(14); although recent studies indicate that the detected microbial signals are likely the result of contamination during sample collection or during DNA extraction and sequencing (15)(16)(17). That controversy about the existence or absence of a microbiome in the placenta and fetus of a healthy pregnancy is not the focus of this review.…”

Epigenetic Changes Induced by Maternal Factors during Fetal Life: Implication for Type 1 Diabetes

“…Other researchers have found that in-utero exposures to environmental factors, such as cigarette smoking during pregnancy [70][71][72], maternal diet [73][74][75][76], and microbial exposures [77,78], also have a dramatic influence on the risk of allergic disease in the offspring by altering fetal lung development and immune function [79]. Results from "The Managing Asthma in Pregnancy (MAP) Study" provided the first demonstration that exposure to maternal asthma during pregnancy is associated with alterations in the DNA methylation profile of infants' peripheral blood.…”