Abstract
Pulmonary fibrosis is a chronic and often fatal disease. The pathogenesis is characterized by aberrant repair of lung parenchyma, resulting in loss of physiological homeostasis, respiratory failure, and death. The immune response in pulmonary fibrosis is dysregulated. The gut microbiome is a key regulator of immunity. The role of the gut microbiome in regulating the pulmonary immunity in lung fibrosis is poorly understood. Here, we determine the impact of gut microbiota on pulmonary fibrosis in substrains of C57BL/6 mice derived from different vendors (C57BL/6J and C57BL/6NCrl). We used germ-free models, fecal microbiota transplantation, and cohousing to transmit gut microbiota. Metagenomic studies of feces established keystone species between substrains. Pulmonary fibrosis was microbiota dependent in C57BL/6 mice. Gut microbiota were distinct by β diversity and α diversity. Mortality and lung fibrosis were attenuated in C57BL/6NCrl mice. Elevated CD4+IL-10+ T cells and lower IL-6 occurred in C57BL/6NCrl mice. Horizontal transmission of microbiota by cohousing attenuated mortality in C57BL/6J mice and promoted a transcriptionally altered pulmonary immunity. Temporal changes in lung and gut microbiota demonstrated that gut microbiota contributed largely to immunological phenotype. Key regulatory gut microbiota contributed to lung fibrosis, generating rationale for human studies.
Authors
Stephen J. Gurczynski, Jay H. Lipinski, Joshua Strauss, Shafiul Alam, Gary B. Huffnagle, Piyush Ranjan, Lucy H. Kennedy, Bethany B. Moore, David N. O’Dwyer
This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.
Having trouble reading a PDF?
PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.
Having trouble saving a PDF?
Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.
Having trouble printing a PDF?
- Try printing one page at a time or to a newer printer.
- Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
- Make sure you are using the latest version of Adobe's Acrobat Reader.
