ThePglyrp1-Regulated Microbiome Enhances Experimental Allergic Asthma

Abstract Changes in intestinal or respiratory microbiomes in infants correlate with increased incidence of asthma, but the causative role of microbiome in the susceptibility to asthma and the host genes that regulate these changes in microbiome are mostly unknown. In this study, we show that decreased responsiveness to allergic asthma in Pglyrp1−/− mice (lacking bactericidal peptidoglycan recognition protein 1) could be transferred to germ-free wild-type mice by colonization of mothers and newborns with microbiota from Pglyrp1−/− mice. These colonized mice had decreased airway resistance and fewer inflammatory cells, less severe histopathology, and lower levels of IgE and proallergic cytokines and chemokines in the lungs. This microbiome-dependent decreased responsiveness to asthma was most pronounced in colonized germ-free BALB/c mice (genetically predisposed to asthma), only partially evident in outbred germ-free Swiss Webster mice, and marginal in conventional BALB/c mice following depletion of microbiome with antibiotics. Mice with a low asthmatic response colonized with microbiota from Pglyrp1−/− mice had increased abundance of Bacteroidetes and decreased abundance of Firmicutes, Tenericutes, Deferribacteres, and Spirochaetes in the feces and increased abundance of Pasteurella in the oropharynx. These changes in bacterial abundance in the feces and oropharynx correlated with lower asthmatic responses in the lungs. Thus, our results show that Pglyrp1 enhances allergic asthmatic responses primarily through its effect on the host intestinal microbiome and identify several bacteria that may increase or decrease sensitivity to asthma. This effect of microbiome is strong in asthma-prone BALB/c mice and weak in asthma-resistant outbred mice and requires germ-free conditions before colonization with microbiota from Pglyrp1−/− mice.