Although the antibiotics caused subtle changes to the infant microbiome, these changes are much less significant than the impact of how the babies were fed. The findings were recently reported in the journal Cell Host & Microbe.
C-section recipients are usually given prophylactic antibiotics just before the procedure to prevent later infections at the surgical site. But there have been concerns about whether these antibiotics have a negative impact on newborns and their microbiomes if the drugs travel through the umbilical cord and reach the baby before the cord is cut.
“We decided to conduct this study because it addresses a significant clinical question with possibly profound implications for infant health,” says first and corresponding author Trishla Sinha. “It is crucial to balance high-quality evidence of immediate benefits to the mother against equally robust evidence of any potential short- and long-term risks to the infant. Mothers often ask whether the antibiotics they take influence their child, and this study can provide assurance that they have only small effects on the infant gut microbiome.”
A handful of previous studies have looked at this question, but in smaller sample sizes. The first part of the current study prospectively enrolled 28 mother-infant pairs. Twelve of the mothers received antibiotics before skin incision. The other 16 received them after the umbilical cord was clamped. In total, 172 infant microbiome samples were collected at 8 different timepoints from birth up to one year of age. The second part of the analysis also included data from two other similar trials for a total of 79 infants.
“Our combined analysis makes this the largest study in the field,” Sinha says. “Additionally, our longitudinal data and deep metagenomic sequencing were unprecedented.”
For the samples they collected, the researchers looked at infant gut microbiome species composition and strain variability, as well as the composition of bacterial antibiotic resistance genes. They also looked at the composition of bile and short-chain fatty acids. In addition to the information about antibiotic usage, the investigators had information about whether the infants were formula-fed or breastfed.
Their results showed that, in general, feeding mode had a significant impact on gut microbial diversity, species, and strain-level bacterial composition, as well as bile acid composition. Infants who were formula-fed had a significantly different overall microbiome profile, with feeding mode explaining 12% of the variation in overall infant gut microbiome composition during the first 6 weeks of life. These differences were also reflected in the bile acid profiles in the stools of these infants. Recent research has highlighted the crucial role of the gut microbiome and bile acids in the development of immune disorders later in life, which suggests that these early-life changes could have important long-term consequences. However, further long-term studies are needed to confirm these findings. In contrast to feeding mode, antibiotics only had subtle impacts on antibiotic resistance genes and strain variability.
“We were surprised that the antibiotics did not drastically alter the microbiome, because other research has reported a large impact of antibiotics on infant gut microbiome composition,” Sinha says. “This is probably due to the fact that it is a one-time exposure to intravenous antibiotics during birth, in contrast to prolonged exposure to antibiotics throughout infancy.”
In their next study, the researchers plan to examine a group of 1,500 mother-infant pairs from the Dutch cohort Lifelines NEXT, looking at various health, environmental, and dietary factors during pregnancy and birth, as well as factors after birth that may influence the infant gut microbiome composition. The researchers plan to follow the infants throughout childhood and into adulthood to assess the long-term impact of the infant gut microbiome on future health outcomes.
“It’s also important to realize that alterations in the gut microbiome do not immediately translate to future health outcomes for the child,” Sinha says. “These still need to be extensively studied in longitudinal studies with longer follow-up times.”
This study is an example of a successful collaboration between the clinical team from the Obstetrics department and the research group from the Genetics department. It highlights the importance of MD/PhD training in generating clinical studies grounded in a strong scientific foundation
