Discovery of infants’ airway microbiomes may help predict lung disease

In contrast to the general belief that the airways of an infant are sterile until after birth, University of Alabama at Birmingham researchers and colleagues have found that the infant airway is already colonised with bacteria or bacterial DNA when a baby is born — and this is true for infants born as early as 24 weeks gestation.

How microbes get into the airways and the purpose of this pre-birth colonisation are still unclear, but the pattern of colonisation appears to have an important link to later severe neonatal lung disease.

An early microbial imbalance, or dysbiosis, is predictive for the development of bronchopulmonary dysplasia, or BPD, a chronic lung disease of prematurity. The extremely low birth-weight, or ELBW, infants in this study had an average birth weight of 1 pound, 8 ounces. Researchers found that the ELBW infants who went on to develop life-threatening BPD showed abnormal microbial colonisation patterns at birth, as compared to pre-term infants who did not get BPD.

“Right at birth, your respiratory microbiome can possibly predict your risk for BPD,” said Charitharth Vivek Lal, M.D., assistant professor in the UAB Pediatrics Division of Neonatology and the lead investigator of this study.
Extremely premature infants are at risk for BPD, which is the most common lung pathology of these tiny infants and a significant cause of morbidity, mortality and health care expenditures. Adults and children who had BPD as infants have lungs that failed to develop properly and are more prone to worse lung function, asthma, lung infections and pulmonary hypertension.

The researchers also looked at the airway microbiomes of 18 ELBW infants with established BPD and found that their microbiomes had a decreased diversity of types of microbes, and the pattern was very different from those of ELBW infants shortly after birth or full-term infants at birth.

As to specific groups of microbes, the phylum Proteobacteria, which includes bacteria like E. coli, appeared to be involved in BPD pathology, and the genus Lactobaccillus, part of the phylum Firmicutes, appeared to be involved in disease protection.

Lal and colleagues found decreased Lactobacillus abundance in the airway microbiomes of 10 infants born to mothers who had chorioamnionitis — an infection of the membranes of the placenta and an independent risk factor for BPD — as well as decreased Lactobacillus abundance at birth in the airways of the BPD-predisposed, ELBW infants, as compared to BPD-resistant infants. Research elsewhere has suggested a beneficial role for Lactobacillus against airway diseases and for lung development.

“I predict that researchers will study the use of respiratory probiotics, and the role of the gut-lung microbiome axis in the future,” Lal said.

For five ELBW infants who later developed BPD, the researchers collected periodic airway microbiome samples from birth through 9 weeks and saw extremely similar patterns of change in the microbiomes over time.

As for the source of the microbes, Lal and colleagues wrote, “As it is commonly believed that colonization of neonates originates in the birth canal, we were surprised to find that the airway microbiome of vaginally delivered and caesarean section-delivered neonates were similar, which suggests that the microbial DNA in the airways is probably transplacentally derived, consistent with reports that the placenta has a rich microbiome.”

The researchers speculate that this transmission of bacteria or bacterial DNA to the in-utero infant could be via blood or amniotic fluid.

University of Alabama at Birmingham www.uab.edu/news/innovation/item/7505-discovery-of-infants-airway-microbiomes-may-help-predict-lung-disease