Alcohol-associated intestinal dysbiosis impairs pulmonary host defense against Klebsiella pneumoniae.

PLoS Pathogens. 2017;13(6):e1006426 DOI 10.1371/journal.ppat.1006426


Journal Homepage

Journal Title: PLoS Pathogens

ISSN: 1553-7366 (Print); 1553-7374 (Online)

Publisher: Public Library of Science (PLoS)

LCC Subject Category: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy | Science: Biology (General)

Country of publisher: United States

Language of fulltext: English

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Derrick R Samuelson

Judd E Shellito

Vincent J Maffei

Eric D Tague

Shawn R Campagna

Eugene E Blanchard

Meng Luo

Christopher M Taylor

Martin J J Ronis

Patricia E Molina

David A Welsh


Peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 24 weeks


Abstract | Full Text

Chronic alcohol consumption perturbs the normal intestinal microbial communities (dysbiosis). To investigate the relationship between alcohol-mediated dysbiosis and pulmonary host defense we developed a fecal adoptive transfer model, which allows us to investigate the impact of alcohol-induced gut dysbiosis on host immune response to an infectious challenge at a distal organ, independent of prevailing alcohol use. Male C57BL/6 mice were treated with a cocktail of antibiotics (ampicillin, gentamicin, neomycin, vancomycin, and metronidazole) via daily gavage for two weeks. A separate group of animals was fed a chronic alcohol (or isocaloric dextrose pair-fed controls) liquid diet for 10 days. Microbiota-depleted mice were recolonized with intestinal microbiota from alcohol-fed or pair-fed (control) animals. Following recolonization groups of mice were sacrificed prior to and 48 hrs. post respiratory infection with Klebsiella pneumoniae. Klebsiella lung burden, lung immunology and inflammation, as well as intestinal immunology, inflammation, and barrier damage were examined. Results showed that alcohol-associated susceptibility to K. pneumoniae is, in part, mediated by gut dysbiosis, as alcohol-naïve animals recolonized with a microbiota isolated from alcohol-fed mice had an increased respiratory burden of K. pneumoniae compared to mice recolonized with a control microbiota. The increased susceptibility in alcohol-dysbiosis recolonized animals was associated with an increase in pulmonary inflammatory cytokines, and a decrease in the number of CD4+ and CD8+ T-cells in the lung following Klebsiella infection but an increase in T-cell counts in the intestinal tract following Klebsiella infection, suggesting intestinal T-cell sequestration as a factor in impaired lung host defense. Mice recolonized with an alcohol-dysbiotic microbiota also had increased intestinal damage as measured by increased levels of serum intestinal fatty acid binding protein. Collectively, these results suggest that alterations in the intestinal immune response as a consequence of alcohol-induced dysbiosis contribute to increased host susceptibility to Klebsiella pneumonia.