Sex-specific alterations in the gut and lung microbiome of allergen-induced mice

Researchers have demonstrated that the microbiome is a driver of illness including respiratory diseases. Much evidence suggests that bacterial metabolites produced in the gut and lung can impact lung inflammation and immune cell activity and that the microbiome plays a role in the pathology of asthma, but most of these reports were not sex-specified. This study aimed to study the alterations in the lung and gut microbiome following allergen exposure in male and female mice. Fecal pellets and lung tissue of male and female C57BL/6J mice exposed intranasally to 25 ug of house dust mite extract (HDM) or 50uL phosphate-buffered saline (PBS) (control) daily for 5 weeks (n=4-6/ treatment group) were collected before starting treatment and at the end of week 5. DNA from fecal pellets and lung tissue was extracted using the ZymoBIOMICS-96 MagBead DNA Kit and analyzed to determine the 16S microbiome: Targeted Metagenomic Sequencing (Zymo Research, Irvine, CA). One taxon, Actinobacteria was common between the gut and lung microbiome. In the gut microbiome, the firmicutes and Bacteroidetes ratio (F: B) was reduced in both male and female HDM-challenged mice but was significantly reduced in the male mice when compared with the pre-exposure values. Alpha diversity analysis showed an increase in median value in the males after 5 weeks of HDM exposure when compared to the pre-exposed group, but this was reversed in females. Our findings showed that only the gut microbiome displayed sex-specific alterations following allergen exposure. However, only the lung microbiome showed treatment-induced alterations. In conclusion, the HDM intranasal challenge alters lung microbiomes and disrupts gut microbiomes in a sex-specific manner.