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Critical Care
Published in: Critical Care 1/2020

01-12-2020 | Antibiotic | Research

Antibiotic-related gut dysbiosis induces lung immunodepression and worsens lung infection in mice

Authors: Rodrigue Dessein, Marvin Bauduin, Teddy Grandjean, Rémi Le Guern, Martin Figeac, Delphine Beury, Karine Faure, Christelle Faveeuw, Benoit Guery, Philippe Gosset, Eric Kipnis

Published in: Critical Care | Issue 1/2020

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Abstract

Background

Gut dysbiosis due to the adverse effects of antibiotics affects outcomes of lung infection. Previous murine models relied on significant depletion of both gut and lung microbiota, rendering the analysis of immune gut-lung cross-talk difficult.
Here, we study the effects of antibiotic-induced gut dysbiosis without lung dysbiosis on lung immunity and the consequences on acute P. aeruginosa lung infection.

Methods

C57BL6 mice received 7 days oral vancomycin-colistin, followed by normal regimen or fecal microbial transplant or Fms-related tyrosine kinase 3 ligand (Flt3-Ligand) over 2 days, and then intra-nasal P. aeruginosa strain PAO1. Gut and lung microbiota were studied by next-generation sequencing, and lung infection outcomes were studied at 24 h. Effects of vancomycin-colistin on underlying immunity and bone marrow progenitors were studied in uninfected mice by flow cytometry in the lung, spleen, and bone marrow.

Results

Vancomycin-colistin administration induces widespread cellular immunosuppression in both the lung and spleen, decreases circulating hematopoietic cytokine Flt3-Ligand, and depresses dendritic cell bone marrow progenitors leading to worsening of P. aeruginosa lung infection outcomes (bacterial loads, lung injury, and survival). Reversal of these effects by fecal microbial transplant shows that these alterations are related to gut dysbiosis. Recombinant Flt3-Ligand reverses the effects of antibiotics on subsequent lung infection.

Conclusions

These results show that gut dysbiosis strongly impairs monocyte/dendritic progenitors and lung immunity, worsening outcomes of P. aeruginosa lung infection. Treatment with a fecal microbial transplant or immune stimulation by Flt3-Ligand both restore lung cellular responses to and outcomes of P. aeruginosa following antibiotic-induced gut dysbiosis.
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Metadata
Title
Antibiotic-related gut dysbiosis induces lung immunodepression and worsens lung infection in mice
Authors
Rodrigue Dessein
Marvin Bauduin
Teddy Grandjean
Rémi Le Guern
Martin Figeac
Delphine Beury
Karine Faure
Christelle Faveeuw
Benoit Guery
Philippe Gosset
Eric Kipnis
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2020
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-020-03320-8

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