Microbial signatures in amniotic fluid at preterm birth and association with bronchopulmonary dysplasia

Abstract

Background Microbiome dysbiosis can have long-lasting effects on our health and induce the development of various diseases. Bronchopulmonary dysplasia (BPD) is a multifactorial disease with pre- and postnatal origins including intra-amniotic infection as main risk factor. Recently, postnatal pathologic lung microbiota colonization was associated with BPD. The objectives of this prospective observational cohort study were to describe differences in bacterial signatures in the amniotic fluid (AF) of intact pregnancies without clinical signs or risk of preterm delivery and AF samples obtained during preterm deliveries and their variations between different BPD disease severity stages. Methods AF samples were collected under sterile conditions during fetal intervention from intact pregnancies (n = 17) or immediately before preterm delivery < 32 weeks (n = 126). Metabarcoding based approaches were used for the molecular assessment of bacterial 16S rRNA genes to describe bacterial community structure. Results The absolute amount of 16S rRNA genes was significantly increased in AF of preterm deliveries and detailed profiling revealed a reduced alpha diversity and a significant change in beta diversity with a reduced relative abundance of 16S rRNA genes indicative for Lactobacillus and Acetobacter while Fusobacterium, Pseudomonas, Ureaplasma and Staphylococcus 16S rRNA gene prevailed. Although classification of BPD by disease severity revealed equivalent absolute 16S rRNA gene abundance and alpha and beta diversity in no, mild and moderate/severe BPD groups, for some 16S rRNA genes differences were observed in AF samples. Bacterial signatures of infants with moderate/severe BPD showed predominance of 16S rRNA genes belonging to the Escherichia-Shigella cluster while Ureaplasma and Enterococcus species were enriched in AF samples of infants with mild BPD. Conclusions Our study identified distinct and diverse intrauterine 16S rRNA gene patterns in preterm infants immediately before birth, differing from the 16S rRNA gene signature of intact pregnancies. The distinct 16S rRNA gene signatures at birth derive from bacteria with varying pathogenicity to the immature lung and are suited to identify preterm infants at risk. Our results emphasize the prenatal impact to the origins of BPD.

The Role of the Airway and Gut Microbiome in the Development of Chronic Lung Disease of Prematurity

“…Despite a robust rebuttal of these papers, which concluded that the detected microbial DNA was more likely to come from contamination of samples than genuine bacterial colonisation [ 36 ], the possible colonisation of the foetus remains a controversial subject. One recent paper analysing bacterial DNA found in amniotic fluid taken during preterm labour unsurprisingly found a greater bacteria load in these samples compared to amniotic fluid taken from pregnancies with intact membranes when labour was not threatened [ 37 ]. As infection is a risk factor for preterm birth, infants exposed to chorioamnionitis or subject to prelabour rupture of membranes may begin colonisation before birth.…”

“…A higher rate of the Escherichia / Shigella cluster in infants with moderate/severe CLD was noted, while less severely affected infants had more Ureaplasma spp. and Enterococcus present [ 37 ]. Several studies have demonstrated very low yields of bacterial DNA detection from respiratory samples taken in the first few days of life [ 25 ], indicating that any colonisation of the respiratory tract before birth is likely to be of extremely low biomass and that established and stable communities of organisms are unlikely to present in the airways during foetal life.…”