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. 2016 Aug 4:6:31023.
doi: 10.1038/srep31023.

The Airway Microbiome at Birth

Charitharth Vivek Lal  1   2   3 , Colm Travers  1 , Zubair H Aghai  4 , Peter Eipers  5 , Tamas Jilling  1   2 , Brian Halloran  1   2 , Waldemar A Carlo  1 , Jordan Keeley  1 , Gabriel Rezonzew  1 , Ranjit Kumar  6 , Casey Morrow  5 , Vineet Bhandari  7 , Namasivayam Ambalavanan  1   2   6
Affiliations

The Airway Microbiome at Birth

Charitharth Vivek Lal et al. Sci Rep. .

Abstract

Alterations of pulmonary microbiome have been recognized in multiple respiratory disorders. It is critically important to ascertain if an airway microbiome exists at birth and if so, whether it is associated with subsequent lung disease. We found an established diverse and similar airway microbiome at birth in both preterm and term infants, which was more diverse and different from that of older preterm infants with established chronic lung disease (bronchopulmonary dysplasia). Consistent temporal dysbiotic changes in the airway microbiome were seen from birth to the development of bronchopulmonary dysplasia in extremely preterm infants. Genus Lactobacillus was decreased at birth in infants with chorioamnionitis and in preterm infants who subsequently went on to develop lung disease. Our results, taken together with previous literature indicating a placental and amniotic fluid microbiome, suggest fetal acquisition of an airway microbiome. We speculate that the early airway microbiome may prime the developing pulmonary immune system, and dysbiosis in its development may set the stage for subsequent lung disease.

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Figures

Figure 1
Figure 1. Comparison of lung microbiota of newborn infants and patients with BPD.
(A) Bar graph depicting the relative abundance of most commonly encountered bacterial phyla between FT, ELBW and BPD infants. (B) Compared to newborn postmenstrual age matched FT infants and ELBW infants, infants with BPD have increased Proteobacteria and decreased Firmicutes and Fusobacteria. (C) Principal coordinates analysis ‘PCoA’ plot (beta diversity) demonstrating unweighted UniFrac distance between samples with sample points colored for ELBW, FT or BPD infants. Samples that are clustered closely together are considered to share a larger proportion of the phylogenetic tree in comparison to samples that are more separated. ELBW and FT infants have similar beta diversity, which is very different from the beta diversity of BPD infants. (D) Shannon diversity index depicting less microbial alpha diversity in infants with BPD compared to FT and ELBW infants.
Figure 2
Figure 2. Genus level lung microbial abundance of ELBW infants, FT infants and patients with BPD.
Heatmap depicting the relative abundance of the most common bacterial families at the genus level. Statistically significant difference in microbial abundance is seen between lung microbiome of ELBW and BPD infants (*) and between FT and BPD infants (#).
Figure 3
Figure 3. Temporal changes in airway microbiome of ELBW infants who develop BPD.
Pie charts showing the changes in airway microbiome with time in 5 ELBW patients (A–E) from birth onwards. In all patients, a relative increase in abundance of Proteobacteria and a relative decrease in abundances of Firmicutes, Actinobacteria, Tenericutes, Bacteroidetes and other microbes, are seen with time.
Figure 4
Figure 4. Early airway microbiome of ELBW infants and its association with development of BPD – Discovery Cohort.
(A) Heat map showing the relative abundance of genera across day 1 samples from ELBW infants who go on to develop BPD (BPD - Predisposed) versus those who do not (BPD Resistant). Abundance of genus Lactobacillus (###) is reduced in BPD - Predisposed group (p = 0.05). (B) Phylum level distribution of lung microbiome shows no major differences between groups. (C) Shannon diversity index alpha diversity is not statistically different between groups (p = 0.18). (D) Bar graph depicting lower abundance of genus lactobacillus in infants born to mothers with chorioamnionitis.
Figure 5
Figure 5. Early airway microbiome of ELBW infants and its association with development of BPD – Validation Cohort.
(A) Heat map showing the relative abundance of genera across day 1 samples from ELBW infants who go on to develop BPD (BPD Predisposed) versus those who do not (BPD Resistant). Abundance of genus Lactobacillus (***) is reduced in BPD Predisposed group (p = 0.04). (B) Phylum level distribution of lung microbiome shows no major differences between groups. (C) Shannon diversity index shows no difference in alpha diversity between groups (p > 0.1).
Figure 6
Figure 6. Early airway Lactobacillus abundance in discovery and validation cohorts.
Bar graphs depicting the relative abundance of Lactobacillus in ELBW infants at birth. In both the discovery cohort and the validation cohort the relative abundance of Lactobacillus is significantly higher in the BPD Resistant infants compared to BPD Predisposed infants (p < 0.05).
Figure 7
Figure 7. Limulus amebocyte lysate chromogenic endotoxin levels in tracheal aspirates of infant.
(A) Endotoxin concentrations are increased in tracheal aspirate samples collected from infants with BPD compared to infants at birth (p < 0.05). (B) No difference was seen in endotoxin amounts in airways of BPD Resistant and BPD Predisposed ELBW infants at birth (p = 0.1).
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