Extremely preterm infants weighing under 3.3 pounds often need high levels of oxygen support due to underdeveloped lungs a factor that contributes to bronchopulmonary dysplasia (BPD) a leading cause of death in these vulnerable newborns. BPD causes lasting damage to their fragile lungs.

In one of the most comprehensive studies to date on gut microorganisms in very preterm babies researchers from the University of Alabama at Birmingham and the University of Tennessee Health Science Center discovered that the composition of gut fungi during the second week of life can predict the development of BPD well before clinical diagnosis. By analyzing the first non-meconium stool samples they found that the fungal microbiome (mycobiome) in infants who later developed BPD showed distinct differences in diversity structure and connectivity compared to those who did not develop the disease. Notably no significant differences were found in the bacterial microbiome at this early stage.

To investigate causality researchers transplanted the first true stool samples either from preterm infants who later developed BPD or from those who did not into female mice creating a pseudo-humanized gut microbiome. In a mouse model of BPD offspring of the mice that received stool from BPD-predictive infants developed more severe lung injury than those whose mothers received stool from no-BPD infants.

In follow-up experiments treating these female mice with an antifungal agent before giving birth reduced lung injury in their pups suggesting that blocking perinatal fungal colonization could be protective. Conversely enhancing fungal colonization with a common Candida species worsened lung damage in newborn pups.

These findings show that the early intestinal fungal microbiome is linked to later development of BPD in preterm infants and that its effects are both transferable and modifiable in animal models said Dr. Kent Willis assistant professor in the UAB Department of Pediatrics. This points to a causal role and positions gut fungi as a potential therapeutic target for neonatal lung disease.

Our findings show that infants who did not develop BPD had a more consistent and uniform gut fungal composition said Dr. Kent Willis. In contrast those who went on to develop BPD had more varied and irregular mycobiomes. This implies that a specific pattern of mycobiome development may be key to protecting against BPD and that deviations from this pattern though diverse are linked to disease onset.

Newborns first pass meconium which is made up of substances ingested in the womb. The first true stools examined in this study during the second week of life are composed of digested milk. While fungi are known to be important and stable components of the adult microbiome Willis and Dr. Ajay Talati note that their non-pathogenic roles especially in newborns are not well understood particularly compared to bacterial communities.

Source: https://www.uab.edu/news/research-innovation/gut-fungi-in-very-low-birthweight-infants-modulate-oxygen-induced-lung-damage