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respiratory disease

Neonatology

Uncovering the Role of the Pulmonary Microbiome in Chronic Respiratory Disease

Say the word microbiome and you probably think about the billions of microbes that inhabit the gut. But Children’s of Alabama neonatologist Charitharth Vivek Lal, M.D., wants you to consider another microbiome — the lung microbiome. Not only does it exist, he and his team have discovered, but it is present as early as birth, even at 24 weeks gestation, negating the long-held believe that the lungs are sterile before birth.

The question he is now trying to answer is what role it plays in the chronic lung disease bronchopulmonary dysplasia (BPD), which affects between 48% to 68% of babies born before 28 weeks of gestation. The condition is a major cause of morbidity and mortality in preterm infants, characterized by lung inflammation, injury and pulmonary hypertension, among other factors.[1]

A study from Lal clearly demonstrated that microbial imbalance, or dysbiosis, predicts the development of BPD in extremely low-birthweight newborns. He and his team evaluated the microbiome of several infants at birth and found diverse and similar airway microbiomes in both, which differed from older preterm infants with BPD.

They found that dysbiotic changes in the airway microbiome at birth correlated with the development of BPD, including lower levels of the “good” bacteria lactobacillus in infants born to mothers with chorioamnionitis, an infection of the membranes of the placenta that is an independent risk factor for BPD. They suggested in their paper that a microbiome signature possibly exists in utero, and that part of its role may be to prime the pulmonary immune system. If dysbiosis occurs, they wrote, “it may set the stage for subsequent lung disease.”

So, said Lal, what about a respiratory probiotic to restore the microbiome?

“If it relieves inflammation, could we use this to replace steroids in various childhood lung diseases?” he asked. Studies in mice using Dr. Lal’s patented ‘respiratory probiotics’ demonstrate benefits. “The next step is to test it in larger animals and then humans,” he said.


[1] Lal CV, Bhandari V, Ambalavanan N.Genomics, Microbiomics, Proteomics and Metabolomics in Bronchopulmonary Dysplasia. Semin Perinatol. 2018 Nov;42(7):425-431.

[2] Lal CV, Kandasamy J, Ramani M, Ambalavanan N. Metabolomic and Metagenomic Signatures of Bronchopulmonary Dysplasia. Am J Physiol Lung Cell Mol Physiol. 2018 Aug 16.

[3] Lal CV, Olave N, Travers C, Halloran H, Rezonzew G, Xu X, Genschmer K, Russell D, Gaggar A, Blalock E, Vineet Bhandari, Ambalavanan N. Exosomal MicroRNA 876-3p Predicts and Protects Against Severe Bronchopulmonary Dysplasia in Extremely Preterm Infants. JCI Insight, 2018; 3(5: e93994). PMID: 29515035

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