Previous research has established that children born by cesarean section have an increased risk of developing asthma compared to children born by vaginal delivery. It has also been shown that babies born by cesarean section have an altered gut microbiota composition. Now, a new paper presents data suggesting that these factors are linked.

The researchers found an increased risk of asthma in children born by cesarean section if their gut microbiota profile at one year of age remained similar to that at birth. No association with asthma risk was found with gut microbiota perturbations that occurred at birth but resolved by one year of age. This suggests that healthy maturation of the gut microbiota may decrease the risk of developing asthma for children born by cesarean section.

The study is published in Science Translational Medicine in the article titled, “Delivery mode associates with the risk of childhood asthma partly through long-term microbial changes in the developing gut.”

The prevalence of cesarean section has increased globally in recent decades. Children born by cesarean section have an increased risk of developing asthma and other immune-mediated diseases compared to children born by vaginal delivery. A link between cesarean section and later disease has been suggested to be mediated through microbial effects.

For the first time, researchers from Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), the University of Copenhagen, Danish Technical University, and Rutgers University describe how delivery by cesarean section leads to a skewed gut microbiome and associates with asthma development in the first six years of life.

Using the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) mother-child cohort, the researchers analyzed the effects of delivery mode on the gut microbiome at multiple time points in the first year of life and to explore whether perturbations of the microbiome can explain the delivery mode-associated risk of developing asthma during childhood.

Following 700 children from birth, the researchers examined the effects of cesarean section delivery on gut microbial composition by 16S rRNA gene amplicon sequencing during the first year of life. They then explored whether gut microbial perturbations due to delivery mode were associated with a risk of developing asthma in the first six years of life.

The authors wrote: “Delivery by cesarean section was accompanied by marked changes in gut microbiota composition at one week and one month of age, but by one year of age only minor differences persisted compared to vaginal delivery.”

Increased asthma risk was found in children born by cesarean section only if their gut microbiota at age one year still carried a cesarean section signature. No associations with asthma existed from the very early though more pronounced microbial perturbations.

“Even though a child is born by cesarean section and has an immense early microbial perturbation, this may not lead to a higher risk of asthma, if the microbiome matures sufficiently before age one year,” said Jakob Stokholm MD, PhD, senior researcher and leader of the microbiome group at COPSAC and first author on the study.

He continued: “Our study proposes the perspective of restoring a cesarean section perturbed microbiome and thereby perhaps prevent asthma development in a child, who is otherwise in high risk. This study provides a mechanism for the known link between C-section birth and heightened risk of asthma: it is a one-two punch—abnormal early microbiota and then failure to mature.”

“This study has implications for understanding the microbiota’s role in asthma development after delivery by cesarean section,” noted Søren J. Sørensen, PhD, professor at the University of Copenhagen, adding that it could “potentially lead to novel prevention strategies and targeted, efficient microbiota manipulation in children who had early perturbations of the microbiome.”

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