Co-development of three systems related to infant respiratory health

A new multidisciplinary study conducted by researchers at the University of Rochester Medical Center has found that the joint development of three systems, the gut microbiome, the respiratory system and the immune system, is correlated with a baby’s respiratory health, and that a baby can have negative respiratory problems . consequences if the development of any of these systems is disrupted.

The Study, “Deviant Newborn” T-cell and microbiota developmental pathways predict respiratory distress during childhood,” it was published in iScience (cell press) and co-authored Kristin Scheible, MD, associate professor in the Departments of Pediatrics and Microbiology and Immunology, and Andrew McDavid, Ph.D., of the Department of Biostatistics and Computational Biology.

The project looked at 148 preterm and 119 full-term infants from birth to one year of age to examine the development of the microbiome, immune system and respiratory system and how this joint development affects a child’s health. These systems usually develop simultaneously and in sync with the baby during the first year of life.

The study found that disruption of one of the three systems resulted in greater respiratory morbidity in infants. In addition, the baby’s postmenstrual age (or weeks from conception) was a more accurate measure of predicting disruption of either system than the time since birth.

“When a baby is born, that’s usually considered day zero for that child. Instead, we modeled it with the baby’s age from the day of conception,” Scheible said. “The immune and microbial development of a 2-month-old baby doesn’t look the same for a baby born at 32 weeks compared to a baby born at 42.”

The implications of using postmenstrual age as a measure could potentially change how clinicians view the risks and benefits of immune or microbially modifying therapies, such as antibiotics or probiotics. This study found that prenatal antibiotics or infection interfere with the developmental trajectory. When babies are exposed to antibiotics – especially premature babies – it increases their risk of respiratory disease in the first year of life.

In addition, health care providers should investigate the use of probiotics and prebiotics, Scheible said. These interventions may not work when introduced on an inappropriate developmental timeline, and clinicians should consider using postmenstrual age as a measure of willingness to see benefit from therapies targeting the microbiome and immune system.

“When you take a baby that was born prematurely and takes away all of the mother’s protection, such as the placenta, it’s critical to know what happens to underdeveloped systems like the microbiome and the immune system. Interventions like intubation, central lines Oxygen and antibiotics are implemented and affect their development, and the impact of disrupting these systems can be magnified in those first two critical weeks for the baby,” Scheible said.

So far, the study found that when the fetus is exposed to antibiotics or infection just before birth, the normal developmental trajectory of the T-cell population is disrupted, and this disruption predicts subsequent airway microbial colonization and respiratory disease. . In addition, the study authors found that when either the microbiome, immune system, or respiratory system is disrupted, the three systems are no longer on a parallel path of development and it takes several years for the affected system to catch up.

We were able to model and measure the development of the immune system and the microbiome and compare it to the patient’s clinical history, and the asynchrony of these systems directly leads to worse respiratory outcomes.”

Andrew McDavid, Ph.D., Department of Biostatistics and Computational Biology, University of Rochester Medical Center

More research will be needed to validate these findings and to establish the mechanisms linking microbial-immune co-development. If confirmed, these results may have important implications for determining the risks/benefits of perinatal antibiotic administration, the optimal timing for immune and microbiota targeting interventions, and for predicting potential respiratory morbidity for exposed pre- and term infants.

“We don’t yet find a panacea to determine who will develop disease. The point is to suggest other models or interventions that can be tried to try and see how the immune system or microbiome can be changed to whatever appropriate window based on age,” says McDavid.


Reference magazine:

McDavid, A., et al. (2022) Abnormal developmental trajectories of newborn T cells and microbiota predict respiratory distress during childhood. iScience.

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