Epigenetic regulation in murine offspring as a novel mechanism for transmaternal asthma protection induced by microbes.

Background: Bronchial asthma is a chronic inflammatory disease resulting from complex gene-environment interactions. Natural microbial exposure has been identified as an important environmental condition that provides asthma protection in a prenatal window of opportunity. Epigenetic regulation is an important mechanism by which environmental factors might interact with genes involved in allergy and asthma development. Objective: This study was designed to test whether epigenetic mechanisms might contribute to asthma protection conferred by early microbial exposure. Methods: Pregnant maternal mice were exposed to the farm-derived gram-negative bacterium Acinetobacter lwoffii F78. Epigenetic modifications in the offspring were analyzed in T(H)1- and T(H)2-relevant genes of CD4(+) T cells. Results: Prenatal administration of A lwoffii F78 prevented the development of an asthmatic phenotype in the progeny, and this effect was IFN-gamma dependent. Furthermore, the IFNG promoter of CD4(+) T cells in the offspring revealed a significant protection against loss of histone 4 (H4) acetylation, which was closely associated with IFN-gamma expression. Pharmacologic inhibition of H4 acetylation in the offspring abolished the asthma-protective phenotype. Regarding T(H)2-relevant genes only at the IL4 promoter, a decrease could be detected for H4 acetylation but not at the IL5 promoter or the intergenic T(H)2 regulatory region conserved noncoding sequence 1 (CNS1). Conclusion: These data support the hygiene concept and indicate that microbes operate by means of epigenetic mechanisms. This provides a new mechanism in the understanding of gene-environment interactions in the context of allergy protection. (J Allergy Clin Immunol 2011;128:618-25.

Supplementary Material for: High Indoor Microbial Levels Are Associated with Reduced Th1 Cytokine Secretion Capacity in Infancy

<b><i>Background:</i></b> Exposure to microbes and their components may affect the maturation of the immune system.<b> </b>We examined the association of house dust microbial content with cytokine-producing capacity at birth and at the age of 1 year. <b><i>Methods:</i></b> Production of TNF-α, IFN-γ, IL-5, IL-8 and IL-10 at birth (n = 228) and at the age of 1 year (n = 200) following 24- and 48-hour whole-blood stimulation with staphylococcal enterotoxin B (SEB), lipopolysaccharide and the combination of phorbol ester and ionomycin was measured. Concentrations of ergosterol (marker for fungal biomass), muramic acid (marker for Gram-positive bacteria) and 3-hydroxy fatty acids with a carbon chain length from 10 to 14 (marker for Gram-negative bacteria) in living room floor dust were analyzed using gas chromatography-tandem mass spectrometry. Five single microbial species or groups were determined using a quantitative polymerase chain reaction method. <b><i>Results:</i></b> A high total level of the studied Gram-positive bacteria in general or <i>Mycobacterium </i>spp. in house dust was associated with decreased SEB-stimulated IFN-γ production, especially at the age of 1 year. The total level of indoor fungi analyzed <i>(Penicillium</i> spp<i>., Aspergillus </i>spp<i>. </i>and<i> Paecilomyces variotii</i> group, <i>Trichoderma viride/atroviride/koningii,</i><i>Wallemia sebi)</i> was also inversely associated with IFN-γ production at the age of 1 year, but this association did not remain significant after adjustment for potential confounders. A few associations were found between microbial exposures and other measured cytokines. <b><i>Conclusions:</i></b> High indoor microbial exposures may affect immune development in early life by reducing T helper type 1 cytokine secretion capacity. The observed hyporesponsiveness may reflect the adaptation of the immune system to environmental antigens. In future, more attention should be paid especially to the immunomodulatory role of exposures to Gram-positive bacteria

Author Correction: Farm-like indoor microbiota in non-farm homes protects children from asthma development (Nature Medicine, (2019), 25, 7, (1089-1095), 10.1038/s41591-019-0469-4).

In the version of this article originally published, several competing interests for Erika von Mutius were missing. This sentence was added to the competing interests section: &ldquo;E.v.M. is an inventor on the patents EP1637147, EP1964570, LU101064 and EP1411977; E.v.M. is an inventor on and has received royalties from the patent EP2361632.&rdquo; The error has been corrected in the HTML and PDF versions of this article

Consumption of unprocessed cow&#39;s milk protects infants from common respiratory infections.

Background: Breast-feeding is protective against respiratory infections in early life. Given the co-evolutionary adaptations of humans and cattle, bovine milk might exert similar anti-infective effects in human infants. Objective: To study effects of consumption of raw and processed cow&#39;s milk on common infections in infants. Methods: The PASTURE birth cohort followed 983 infants from rural areas in Austria, Finland, France, Germany, and Switzerland, for the first year of life, covering 37,306 person-weeks. Consumption of different types of cow&#39;s milk and occurrence of rhinitis, respiratory tract infections, otitis, and fever were assessed by weekly health diaries. C-reactive protein levels were assessed using blood samples taken at 12 months. Results: When contrasted with ultra-heat treated milk, raw milk consumption was inversely associated with occurrence of rhinitis (adjusted odds ratio from longitudinal models [95% CI]: 0.71 [0.54-0.94]), respiratory tract infections (0.77 [0.59-0.99]), otitis (0.14 [0.05-0.42]), and fever (0.69 [0.47-1.01]). Boiled farm milk showed similar but weaker associations. Industrially processed pasteurized milk was inversely associated with fever. Raw farm milk consumption was inversely associated with C-reactive protein levels at 12 months (geometric means ratio [95% CI]: 0.66 [0.45-0.98]). Conclusions: Early life consumption of raw cow&#39;s milk reduced the risk of manifest respiratory infections and fever by about 30%. If the health hazards of raw milk could be overcome, the public health impact of minimally processed but pathogen-free milk might be enormous, given the high prevalence of respiratory infections in the first year of life and the associated direct and indirect costs