Intestinal microbiome dysbiosis increases Mycobacteria pulmonary colonization in mice by regulating the Nos2-associated pathways
MeiQing Han,
Xia Wang,
Lin Su,
Shiqi Pan,
Ningning Liu,
Duan Li,
Liang Liu,
JunWei Cui,
Huajie Zhao,
Fan Yang
Affiliations
MeiQing Han
Department of Tuberculosis, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China; Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical University, Xinxiang, China
Xia Wang
Department of Tuberculosis, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China
Lin Su
Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical University, Xinxiang, China
Shiqi Pan
Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical University, Xinxiang, China
Ningning Liu
Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical University, Xinxiang, China
Duan Li
Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical University, Xinxiang, China
Liang Liu
Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical University, Xinxiang, China
JunWei Cui
Department of Tuberculosis, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China
Huajie Zhao
Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical University, Xinxiang, China
Department of Tuberculosis, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China; Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical University, Xinxiang, China
Increasing researches reveal gut microbiota was associated with the development of tuberculosis (TB). How to prevent or reduce Mycobacterium tuberculosis colonization in the lungs is a key measure to prevent TB. However, the data on gut microbiota preventing Mycobacterium 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 Mycobacterium’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 Mycobacterium colonization in the lungs of mice. The potential mechanisms were gut microbiota dysbiosis altered the lung transcriptome and increased Nos2 expression through the ‘gut–lung axis’. Nos2 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 Defb1 in the cells, and promoting Mycobacteria colonization in the lungs of mice. The present study raises a potential strategy for reducing the risks of Mycobacteria infections and transmission by regulating the gut microbiome balance.
