Pathophysiological role of respiratory dysbiosis in hospital-acquired pneumonia

Roquilly, Antoine; Torres, Antoni; Villadangos, José A; Netea, Mihai G.; Dickson, Robert P.; Becher, Burkhard; Asehnoune, Karim

doi:10.1016/s2213-2600(19)30140-7

Cited by 73 publications

(63 citation statements)

References 94 publications

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“…Contrary to emerging controversial postulates [18], the gut microbiota, independently from the lung microbiota, might be crucial to developing an appropriate lung immune response as suggested by our results restricted to oral vancomycin-colistin and P. aeruginosa strain PAO1 in mice. In this speci c murine model, treating antibiotic-induced dysbiosis through FMT or treating the associated lung immune depression through Flt3-Ligand restore P. aeruginosa (PAO1 strain) lung infection outcomes in mice, and may be potential directions for translational research.…”

Section: Resultscontrasting

confidence: 60%

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

Dessein

Bauduin

Grandjean

et al. 2020

Preprint

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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 intranasal P. aeruginosa strain PAO1. Gut and lung microbiota were studied by next-generation sequencing, and lung infection outcomes were studied at 24h. 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 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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Section: Resultscontrasting

confidence: 60%

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

Dessein

Bauduin

Grandjean

et al. 2020

Preprint

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“…The pathophysiology of nosocomial pneumonia relies on the paradigm of pharyngeal bacterial aspirations, which considers the healthy distal airways to be sterile site that is contaminated by micro-aspiration of digestive contents during the hospital stay. Furthermore, patients admitted to hospital demonstrate a severe impairment of respiratory physiology [24], which is influenced by the patient's medical conditions (e.g. main disease and comorbidities) and therapeutic interventions (e.g.…”

Section: Pathophysiologymentioning

confidence: 99%

Is ventilated hospital-acquired pneumonia a worse entity than ventilator-associated pneumonia?

et al. 2020

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IntroductionNosocomial pneumonia develops after ≥48 h of hospitalisation and is classified as ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP); the latter may require mechanical ventilation (V-HAP) or not (NV-HAP).Main findingsVAP and HAP affect a significant proportion of hospitalised patients and are characterised by poor clinical outcomes. Among them, V-HAP has the greatest 28-day mortality rate followed by VAP and NV-HAP (27.8% versus 18% versus 14.5%, respectively). However, no differences in terms of pathophysiology, underlying microbiological pathways and subsequent therapy have been identified. International guidelines suggest specific flow charts to help clinicians in the therapeutic management of such diseases; however, there are no specific recommendations beyond VAP and HAP classification. HAP subtypes are scarcely considered as different entities and the lack of data from the clinical scenario limits any final conclusion. Hopefully, recent understanding of the pathophysiology of such diseases, as well as the discovery of new therapies, will improve the outcome associated with such pulmonary infections.ConclusionNosocomial pneumonia is a multifaced disease with features of pivotal interest in critical care medicine. Due to the worrisome data on mortality of patients with nosocomial pneumonia, further prospective studies focused on this topic are urgently needed.

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Section: Resultsmentioning

confidence: 72%

Antibiotic-related Gut Dysbiosis Induces Lung Immunodepression and Worsens Lung Infection.

Dessein

Bauduin

Grandjean

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundGut 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.MethodsC57BL6 mice were administered 7 days oral vancomycin-colistin, modulated or not by fecal microbial transplant or exogenous hematopoietic cytokine, Fms-related tyrosine kinase 3 ligand (Flt3-Ligand), followed by intranasal P. aeruginosa strain PAO1. Gut and lung microbiota were studied by next-generation sequencing, and lung infection outcomes were studied at 24h. 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.ResultsVancomycin-colistin administration induces widespread cellular immunosuppression in both 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. ConclusionsThese 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.

show abstract

Pathophysiological role of respiratory dysbiosis in hospital-acquired pneumonia

Cited by 73 publications

References 94 publications

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

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

Is ventilated hospital-acquired pneumonia a worse entity than ventilator-associated pneumonia?

Antibiotic-related Gut Dysbiosis Induces Lung Immunodepression and Worsens Lung Infection.

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