The Immune Response: Birth Mode and Microbiome

Both inside and out, our bodies harbour a huge array of micro-organisms. While bacteria are the biggest players, we also host single-celled organisms known as archaea, as well as fungi, viruses and other microbes – including viruses that attack bacteria. Together these are dubbed the human microbiota. Your body’s microbiome is all the genes your microbiota contains, however colloquially the two terms are often used interchangeably.”

Microbe colonization starts early during human development. “The fetus does not reside in a sterile intrauterine environment and is exposed to commensal bacteria from the maternal gut/blood stream which crosses the placenta and enters the amniotic fluid. This intestinal exposure to colonizing bacteria continues at birth and during the first year of life and has a profound influence on lifelong health. Why is this important? Intestinal crosstalk with colonizing bacteria in the developing intestine affects the infant’s adaptation to extrauterine life (immune homeostasis) and provides protection against disease expression (allergy, autoimmune disease, obesity, etc.) later in life. Colonizing intestinal bacteria are critical to the normal development of host defense.”

Photo by Omar Lopez on Unsplash

Although some scientists doubt that microbial colonization starts during intrauterine life, it is commonly accepted that an extensive exposure to microbial communities of fecal, vaginal, skin and environmental origins occurs at birth, and that this event has a major impact on the colonization of the neonatal gut.

Research findings show that during a natural vaginal birth, specific bacteria from the mother’s gut are passed on to the baby and stimulate the baby’s immune responses. However, this transmission is impacted in children born by caesarean section. The study (Birth mode is associated with earliest strain-conferred gut microbiome functions and immunostimulatory potential) has been published in the scientific journal Nature Communications on November 30, 2018.

Paul Wilmes, senior author of the study, said in a press release: “We find specific bacterial substances that stimulate the immune system in vaginally born babies. In contrast, the immune stimulation in caesarean children is much lower either because the bacterial triggers are present at much lower levels or other bacterial substances hamper these initial immune reactions to happen.”

For the study, the researchers analyzed the structure and function of gut microbial communities in newborn babies and their mothers using metagenomic analysis—and comparing neonates delivered vaginally with those delivered through cesarean section. The study results show differences between the microbiomes of the vaginally delivered neonates and the microbiomes of the neonates delivered through cesarean section. The researchers found that in vaginally delivered babies several functional pathways are over-represented as compared to the neonates delivered through cesarean section. The lipopolysaccharide (LPS) biosynthesis is one of the over-represented functional pathways, and this over-representation appears to be the result of specific bacterial strains that are transmitted from mothers to neonates during vaginal delivery.

The researchers stimulated primary human immune cells with LPS isolated from early stool neonatal samples, and found higher levels of tumour necrosis factor (TNF-α) and interleukin 18 (IL-18) production in cells stimulated with stool samples from vaginally delivered neonates as compared to cells stimulated with stool samples from neonates delivered through cesarean section. Accordingly, the researchers observed higher levels of TNF-α and IL-18 in neonatal blood plasma from vaginally delivered babies.

The researchers conclude that cesarean section delivery disrupts mother-to-neonate transmission of specific microbial strains, thus affecting immune stimulation during a critical window for the priming of the neonatal immune system.

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