The microbiome is a diverse ecosystem that includes all host-associated microorganisms and their genomes. These microorganisms belong to various kingdoms including some potential pathogens such as bacteria, viruses and fungi. To obtain a comprehensive view of the lung microbiome, including not only bacterial but also viral and fungal data, is of great value to improve our understanding of critical lung illnesses such as VAP or ARDS. The evolution of the lung microbiome over time and the description of its dysbiosis will be key elements to improve diagnosis and preventive measures in ventilated patients.
1. Lung Microbiome in Critically Ill Patients
1.1. Lung Bacterial Microbiota
1.1.1. Lung Bacterial Microbiota and Invasive Mechanical Ventilation
Studies to date have been mostly descriptive. A first work demonstrated in 2007 the considerable diversity of microbial populations in bronchial aspirates collected from ventilated patients colonized with
P. aeruginosa [
5]. Since high-throughput sequencing was not gold standard, this very first study used 16S-rRNA clone libraries (PCR amplification, cloning into a vector and sequencing). In 2012, based on a similar methodology for bacterial identification, Bousbia et al. also observed a high bacterial diversity in bronchoalveolar lavage (BAL) from ICU patients mostly ventilated for community-acquired pneumonia [
6]. A large repertoire of 146 bacterial species belonging to seven phyla was identified, of which 73 bacterial species had never been described in infected lungs. Subsequently, most studies used high-throughput sequencing of 16S-rDNA hypervariable sequences to explore the lung microbiota. Smith et al. studied the microbiota of 15 uninfected ventilated patients admitted to a surgical unit whose BAL was negative in conventional culture [
7]. The same phyla were identified in BAL using sequencing of the V4 hypervariable region of 16S-rRNA genes with an Ion Torrent
® sequencer. Most patients had profiles with a high degree of alpha diversity, and inter-individual variation was mostly apparent at the genus level (species diversity within a sample from a given individual). These data were snapshots at a given time point, and the question of how the respiratory microbiota changes under mechanical ventilation overtime, likely the most relevant element, has been addressed in more recent works.
1.1.2. Lung Bacterial Microbiota and Acute Respiratory Distress Syndrome
Beyond the specific effect of mechanical ventilation on the lung microbiota, acute respiratory distress syndrome (ARDS) or severe systemic inflammatory response syndrome (SIRS) may have an impact on its composition, directly or by enrichment from the gut microbiome [
4]. Only a few studies have explored these aspects in critically ill patients. However, the relationship between the gut and the lung microbiome has been well described in asthma or cystic fibrosis and is referred to as the “gut−lung” axis [
3,
10].
Table 1 summarizes the results of the different comparative studies. Further studies, with comparable methodologies, are needed to better characterize the role of the different actors in the vicious circle between dysbiosis, inflammation and lung injury, and to determine the role of enrichment of the lung microbiota with bacteria from the gut microbiota.
Table 1. Main comparative studies exploring the lung microbiota in ventilated patients with acute respiratory distress syndrome.
Study |
Enrolled Patients |
Methods (Sampling and Sequencing) |
Main Results |
Panzer et al., 2018 [13] |
30 ventilated patients (severe blunt traumatism) - 13 ARDS 1 patients - 17 non-ARDS patients |
ETA 2 on admission and 24 h after V4 16s-rRNA MiSeq Illumina sequencer |
- Association between ARDS development and lung community composition at 48 h (r2 = 0.08, p = 0.04) - ARDS patients: microbiota enriched with Enterobacteriaceae, Prevotella and Fusobacterium |
Kyo et al., 2019 [14] |
47 ventilated patients: - 40 ARDS - 7 non-ARDS |
BAL 3 within 24 h after intubation V5-6 16s-rRNA Ion One Touch sequencer |
- Decreased alpha diversity in ARDS patient compared to controls (p = 0.031) - Copy number of 16S rRNA gene of Betaproteobacteria decreased in non-surviving (n = 16) vs. surviving patient (n = 24). (106 vs. 104; p < 0.05) |
Dickson et al., 2020 [11] |
91 ventilated patients - 17 ARDS - 84 non-ARDS |
BAL within 24 h of ICU admission V4 16s-rRNA MiSeq Illumina sequencer |
- Increased relative abundance of Enterobacteriaceae in ARDS patient (12.5% vs. 0.8%) (p = 0.002). - Association between presence of gut associated bacteria in the lung microbiota and the ventilator-free days at day 28 (p = 0.003) |
Schmitt et al., 2020 [15] |
30 ventilated patients (surgical) - 15 patients with sepsis-induced ARDS - 15 controls |
BAL at ARDS onset (D0 4, D5 5, D10) V4 16s-rRNA MiSeq Illumina sequencer |
- Lower alpha diversity in BAL of ARDS patients vs. controls (Shannon index 3 (2;3.6) vs. 1 (0.5;1.5); p = 0.007) - Decrease in anaerobic bacteria Prevotella spp (p = 0.0033) and Veillonella spp (p = 0.0002) in ARDS patient - Decreased alpha diversity associated with increased length of mechanical ventilation (ρ = −0.48, p = 0.009) |
This entry is adapted from the peer-reviewed paper 10.3390/life12010007