Joint development of three systems related to the respiratory health of the baby

A new multidisciplinary study conducted by researchers at the University of Rochester Medical Center found that the joint development of three systems, the intestinal microbiome, the respiratory system and the immune system, is linked to a baby’s respiratory health. results if the development of one of these systems is impaired.

The study “Aberrant trajectories of T-cell development and neonatal microbiota predict respiratory compromise in early childhood” was published in iScience (Cell Press) and is a co-author of Christine Scheibel, Ph.D., 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 examines 148 premature and 119 full-term babies from birth to one year to study the development of the microbiome, immune and respiratory systems and how this joint development affects the child’s health. These systems usually develop simultaneously and in sync with the baby in the first year of life.

The study found that disruption of any of the three systems led to higher respiratory morbidity in infants. In addition, the baby’s postmenstrual age (or weeks of conception) is a more accurate benchmark for predicting disruption of any of the systems than the time after birth.

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

The consequences of using postmenstrual age as a benchmark could potentially change the way clinicians view the risks and benefits of immune or microbial-modifying therapies, such as antibiotics or probiotics. This study found that prenatal antibiotics or infection disrupted the development trajectory. If babies are exposed to antibiotics – especially premature babies – this increases the risk of respiratory disease in the first year of life.

In addition, caregivers should study the use of pro and prebiotics, according to Scheible. These interventions may not work when introduced into an inappropriate development schedule, and clinicians should consider using postmenstrual age as a measure of readiness to see the benefits of microbiome and immune system therapies.

“When you take a baby who is born prematurely and remove all the mother’s defenses, such as the placenta, it is extremely important to know what happens to underdeveloped systems such as the microbiome and the immune system. Interventions such as intubation, midline, oxygen and antibiotics are being applied and influenced, and the effects of disruptions on these systems may be more widespread in the first two critical weeks for the baby, “said Shable.

To date, the study found that when the fetus is exposed to antibiotics or infection immediately before birth, the normal trajectory of the T cell population is disrupted, and this disorder predicts subsequent colonization of respiratory microbes and respiratory disease. In addition, the authors of the study found that when the microbiome, immune or respiratory system is disrupted, the three systems are no longer on a parallel path of development and take several years to catch up with the affected system.

We were able to model and measure the development of immunity and the microbiome and compare it with the patient’s clinical history, and the asynchrony of these systems directly leads to poorer respiratory outcomes. “

Andrew McDavid, PhD, Department of Biostatistics and Computational Biology, University of Rochester Medical Center

More research will be needed to confirm these findings and to determine the mechanisms linking microbial-immune co-development. If confirmed, these results could have major implications for determining the risk / benefits of perinatal antibiotic administration, the optimal time for immune and microbiotic interventions, and the prediction of potential respiratory morbidity in preterm and term infants.

“We still can’t find a magic bullet to determine who will develop the disease. The usefulness is to suggest other models or interventions that can be tested to try to see how the immune system or microbiome can be modified in which appropriate window based on age, “said McDavid.

Source:

University of Rochester Medical Center

Reference journal:

McDavid, A., et al. (2022) Aberrant T cell development trajectories and neonatal microbiota predict respiratory compromise in early childhood. iScience. doi.org/10.1016/j.isci.2022.104007.

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