Intestinal microbiome dysbiosis increases pulmonary colonization in mice by regulating the associated pathways.

Increasing researches reveal gut microbiota was associated with the development of tuberculosis (TB). How to prevent or reduce colonization in the lungs is a key measure to prevent TB. However, the data on gut microbiota preventing colonization in the lungs were scarce. Here, we established the clindamycin-inducing intestinal microbiome dysbiosis and fecal microbial transplantation models in mice to identify gut microbiota's effect on 's colonization in the mouse lungs and explore its potential mechanisms. The results showed that clindamycin treatment altered the diversity and composition of the intestinal bacterial and fungal microbiome, weakened the trans-kingdom network interactions between bacteria and fungi, and induced gut microbiome dysbiosis in the mice. Gut microbiota dysbiosis increases intestinal permeability and enhances the susceptibility of colonization in the lungs of mice. The potential mechanisms were gut microbiota dysbiosis altered the lung transcriptome and increased expression through the 'gut-lung axis'. high expression disrupts the intracellular antimicrobial and anti-inflammatory environment by increasing the concentration of nitric oxide, decreasing the levels of reactive oxygen species and in the cells, and promoting colonization in the lungs of mice. The present study raises a potential strategy for reducing the risks of infections and transmission by regulating the gut microbiome balance.