Intestinal microbiome dysbiosis increasesMycobacteriapulmonary colonization in mice by regulating theNos2-associated pathways

Increasing researches reveal gut microbiota was associated with the development of tuberculosis. How to prevent or reduceMycobacterium tuberculosiscolonization in the lungs is a key measure to prevent tuberculosis. However, the data on gut microbiota preventingMycobacteriumcolonization 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 onMycobacterium’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 ofMycobacteriumcolonization in the lungs of mice. The potential mechanisms were gut microbiota dysbiosis altered the lung transcriptome and increasedNos2expression through the “gut-lung axis”.Nos2high expression disrupts the intracellular antimicrobial and anti-inflammatory environment by increasing the concentration of NO, decreasing the levels of ROS andDefb1in the cells, and resulting in promotingMycobacteriacolonization in the lungs of mice. The present study raises a potential strategy for reducing the risks ofMycobacteriainfections and transmission by regulating the gut microbiome balance.