Article Text

PDF

Original article
The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia
  1. Tim J Schuijt1,2,3,
  2. Jacqueline M Lankelma1,
  3. Brendon P Scicluna1,
  4. Felipe de Sousa e Melo1,
  5. Joris J T H Roelofs4,
  6. J Daan de Boer1,
  7. Arjan J Hoogendijk1,
  8. Regina de Beer1,
  9. Alex de Vos1,
  10. Clara Belzer5,
  11. Willem M de Vos5,6,
  12. Tom van der Poll1,2,
  13. W Joost Wiersinga1,2
  1. 1Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  2. 2Department of Medicine, Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  3. 3Department of Clinical Chemistry, Hematology and Immunology, Diakonessenhuis Utrecht, The Netherlands
  4. 4Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  5. 5Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
  6. 6Department of Bacteriology & Immunology, Helsinki University, Helsinki, Finland
  1. Correspondence to Dr W Joost Wiersinga, Department of Medicine, Division of Infectious Diseases, Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room G2-130, Amsterdam 1105 AZ, The Netherlands; w.j.wiersinga{at}amc.uva.nl.

Abstract

Objective Pneumonia accounts for more deaths than any other infectious disease worldwide. The intestinal microbiota supports local mucosal immunity and is increasingly recognised as an important modulator of the systemic immune system. The precise role of the gut microbiota in bacterial pneumonia, however, is unknown. Here, we investigate the function of the gut microbiota in the host defence against Streptococcus pneumoniae infections.

Design We depleted the gut microbiota in C57BL/6 mice and subsequently infected them intranasally with S. pneumoniae. We then performed survival and faecal microbiota transplantation (FMT) experiments and measured parameters of inflammation and alveolar macrophage whole-genome responses.

Results We found that the gut microbiota protects the host during pneumococcal pneumonia, as reflected by increased bacterial dissemination, inflammation, organ damage and mortality in microbiota-depleted mice compared with controls. FMT in gut microbiota-depleted mice led to a normalisation of pulmonary bacterial counts and tumour necrosis factor-α and interleukin-10 levels 6 h after pneumococcal infection. Whole-genome mapping of alveolar macrophages showed upregulation of metabolic pathways in the absence of a healthy gut microbiota. This upregulation correlated with an altered cellular responsiveness, reflected by a reduced responsiveness to lipopolysaccharide and lipoteichoic acid. Compared with controls, alveolar macrophages derived from gut microbiota-depleted mice showed a diminished capacity to phagocytose S. pneumoniae.

Conclusions This study identifies the intestinal microbiota as a protective mediator during pneumococcal pneumonia. The gut microbiota enhances primary alveolar macrophage function. Novel therapeutic strategies could exploit the gut–lung axis in bacterial infections.

  • BACTERIAL INFECTION
  • BACTERIAL PATHOGENESIS
  • IMMUNOLOGY
  • SEPSIS
  • INTESTINAL MICROBIOLOGY

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

View Full Text

Statistics from Altmetric.com

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles

  • Commentary
    Sylvia Knapp