Table 3.

Studies concerning lung microbiota of mechanically ventilated patient and ventilator-associated pneumonia

Authors	Study design	Number of enrolled patients	Subgroups	Samples	Size effect and statistical significance	Negative result
Smith et al. 2016	Prospective study	MV patients in a surgical ICU ventilated more than 36 h	5 MV patient with suspected VAP 10 patients without VAP	BAL after 36 h of mechanical ventilation or in case of VAP suspicion	55 total genera identified in the common microbiome samples 20 genera with abundance > 1%	No comparison between groups
Bousbia et al. 2012		185 pneumonia patients 25 control patient	32 CAP 106 VAP 22 NV-ICU pneumonia 25 aspiration pneumonia	ETA on admission and at 24 h	93/106 VAP patients had a positive BAL by molecular assays 48 had an association of two type of microorganisms between bacteria virus and fungi 146 different bacteria belonging to seven different phyla composed the bacterial lung microbiota of patients Fungal microbiota from pneumonia patients showed the presence of 22 different new fungal species belonging to 2 phyla not previously identified Bacilli and Gammaproteobacteria were dominant in patients, whereas anaerobic bacteria related to Bacteroidia and Clostridia were dominant in controls n bacterial microbiota (p < 0.01)	No specific pattern depending on the type of pneumonia
Kelly et al. 2016	Prospective study	15 MV patients from medical intensive care unit versus healthy unventilated patients 4 patients with CAP/HAP	4 patients with CAP/HAP 4 patients with aspiration at enrollment 4 patients with VAP	ETA and OS within 24 h of orotracheal intubation and every 72 h after	Lower alpha diversity in intubated patients than healthy controls (p = 2.3 × 10−13) Alpha diversity decreased with time in URT of VAP patient (Shannon index = 4 on day 0 versus Shannon index = 3,1 beyond day 0: p = 0.0015) Alpha diversity decreased with time in LRT of VAP patient (Shannon index = 3 on day 0 versus Shannon index = 1,9 beyond day 0: p = 0.13) Higher beta diversity in MV patients’ group than in control group Lower alpha diversity in LRT of VAP patient compared to MV patient with prolonged courses of intubation without infection (p = 0.08)
Zakharkina et al. Thorax 2017	Post hoc analysis of patients initially included in an international multicentre prospective observational cohort study		11 patients with VAP 18 patients without VAP 6 HAP/CAP	BAL for VAP suspicion ETA at ICU admission and twice a week after admission	Association between duration of MV and decreased in Shannon diversity; fixed effect regression coefficient (β): − 0.03 CI 95% [− 0.05; − 0.005] Statistical difference in Weighted Unifrac distance between VAP patient and control patient without colonized airways 0.4 (0.25; 0.5) vs. 0.65 (0.5;0.85), p = 0.02 Increase of β diversity for VAP patients is statistically higher analyzed by PCo analysis (p = 0.03) Acinetobacter, Pseudomonas, Staphyloccocus, and Burkholderia are genera correlated with changes in β diversity	No statistical difference in Weighted Unifrac distance between VAP patient and colonized patient
Emonet et al. 2019	Case control study nested in a prospective single center cohort study	MV adult patient intubated less than 24 h in polyvalent ICU	16 late onset confirmed VAP patient 38 matched control	- ETA and OPS at five time points during MV D0 (of intubation), D3 (3 days after intubation, DVAP-3 (3 days before VAP) DVAP (day of VAP diagnosis), DVAP + 3 (3 days after VAP)	Progressive increase in Proteobacteria (25% on D0 vs. 55% on DVAP + 3) and decreased in Firmicutes (40% vs. 30%) in OS and ETA of VAP patient The absolute abundance of the class Bacilli was significantly higher in ETA from controls at D0. At D0 class Bacilli had a relative abundance > 12% in 82.8% of controls but only in 18.8% of VAP patients. (p < 0.0001) Quantity of human DNA in ETA are significantly higher for VAP patients than in controls. A cutoff of 124.7 ng/μL allowed to differentiate VAP vs controls with a sensitivity of 94.1% and a specificity of 83.3%	General trend of changes in β-diversity during MV are not different between VAP patients and control No significant changes of ETA or OS microbiota between VAP patient and control patient at any time point No lower respiratory tract microbiota markers of VAP clearly identified

MV patients mechanically ventilated patients, BAL bronchoalveolar lavage, ETA endotracheal aspirate, OS oropharyngeal swab, URT upper respiratory tract, LRT lower respiratory tract, VAP ventilator associated pneumonia, CAP community acquired pneumonia, HAP hospital acquired pneumonia, D day