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

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

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere1006426
JournalPLoS pathogens
Volume13
Issue number6
DOIs
StatePublished - Jan 1 2017

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Dysbiosis
Klebsiella pneumoniae
Alcohols
Lung
Microbiota
Klebsiella Infections
Allergy and Immunology
T-Lymphocytes
Fatty Acid-Binding Proteins
Neomycin
Klebsiella
Adoptive Transfer
Metronidazole
Vancomycin
Ampicillin
Gentamicins
Inbred C57BL Mouse
Respiratory Tract Infections
Alcohol Drinking
Blood Proteins

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Samuelson, D. R., Shellito, J. E., Maffei, V. J., Tague, E. D., Campagna, S. R., Blanchard, E. E., ... Welsh, D. A. (2017). Alcohol-associated intestinal dysbiosis impairs pulmonary host defense against Klebsiella pneumoniae. PLoS pathogens, 13(6), [e1006426]. https://doi.org/10.1371/journal.ppat.1006426

Alcohol-associated intestinal dysbiosis impairs pulmonary host defense against Klebsiella pneumoniae. / Samuelson, Derrick R.; Shellito, Judd E.; Maffei, Vincent J.; Tague, Eric D.; Campagna, Shawn R.; Blanchard, Eugene E.; Luo, Meng; Taylor, Christopher M.; Ronis, Martin J.J.; Molina, Patricia E.; Welsh, David A.

In: PLoS pathogens, Vol. 13, No. 6, e1006426, 01.01.2017.

Research output: Contribution to journalArticle

Samuelson, DR, Shellito, JE, Maffei, VJ, Tague, ED, Campagna, SR, Blanchard, EE, Luo, M, Taylor, CM, Ronis, MJJ, Molina, PE & Welsh, DA 2017, 'Alcohol-associated intestinal dysbiosis impairs pulmonary host defense against Klebsiella pneumoniae', PLoS pathogens, vol. 13, no. 6, e1006426. https://doi.org/10.1371/journal.ppat.1006426
Samuelson, Derrick R. ; Shellito, Judd E. ; Maffei, Vincent J. ; Tague, Eric D. ; Campagna, Shawn R. ; Blanchard, Eugene E. ; Luo, Meng ; Taylor, Christopher M. ; Ronis, Martin J.J. ; Molina, Patricia E. ; Welsh, David A. / Alcohol-associated intestinal dysbiosis impairs pulmonary host defense against Klebsiella pneumoniae. In: PLoS pathogens. 2017 ; Vol. 13, No. 6.
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