Caesarean birth impacts newborn’s immune system

Changed microbiome after caesarean birth impacts infant’s immune system, research by Luxembourg Centre for Systems Biomedicine finds

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LUXEMBOURG—Together with colleagues from Sweden and Luxembourg, scientists from the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg have observed that, during a natural vaginal birth, specific bacteria from the mother’s gut are passed on to the infant and stimulate the baby’s immune responses. This transmission is impacted in children born by caesarean section.
“This may explain why, epidemiologically speaking, caesarean-born children suffer more frequently from chronic, immune system-linked diseases compared to babies born vaginally,” says the head of the study Prof. Paul Wilmes, head of the Eco-Systems Biology research group at the LCSB. His team has now published the results in the journal Nature Communications
“In line with the broad taxonomic differences between VD [vaginal delivery] and CSD [caesarean section delivery], our findings demonstrate that CSD significantly affects the functional gene complement of the earliest neonatal gut microbiome by impeding the vertical transfer of specific bacterial strains from the maternal gut microbiome to the neonate,” notes the article. “Consequently, the gut of CSD neonates is most likely colonized by strains derived from other sources, such as breast milk, skin or saliva, as suggested in previous studies. Notably, a selection of enteric strains from the mother was found to be exclusively transferred to the VD neonate (e.g., Bacteroidetes).”
Humans are born germ-free, but birth is normally the time when vitally important bacteria start to colonize the body — including the gut, skin and lungs. Researchers have long suspected that this early colonization sets the course for one’s later health. It could be, however, that a caesarean section prevents certain bacteria, which ordinarily interacts with an infant’s immune system, from being passed on from the mother to the newborn.
Wilmes and his colleagues have now found the first evidence of this in a study of newborns - half of whom were delivered by caesarean section. “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,” he reported.
This bacterial colonizer-immune system link — together with other factors — could explain why babies born by caesarean section are statistically more prone to develop allergies, chronic inflammatory diseases and metabolic diseases. “It could be that the immune system of these children is set on a different path early on," suggested Wilmes. “We now want to further investigate this link mechanistically and find ways by which we might replace the lacking maternal bacterial strains in caesarean-born babies, e.g. by administering probiotics.”
“[…]we observed that several functional pathways were significantly under-represented in CSD neonates, while these were in turn enriched in VD neonates and linked to vertically transmitted strains, in particular the LPS biosynthesis pathway. LPS, an outer surface membrane component of Gram-negative bacteria, promotes the secretion of pro-inflammatory cytokines and thereby sits at the interface of the earliest gut microbiome colonization and neonatal immune system priming,” the article says. “Following the apparent enrichments in LPS biosynthesis in VD neonates due to higher amounts of Gram-negative bacteria, the subsequent extraction and quantification of LPS from neonatal stool and stimulation of primary human immune cells therewith demonstrated a reduced immunostimulatory potential of the earliest gut microbiome in CSD neonates. The differences in earliest immune system priming may result in persistent effects on human physiology in later life, which has also been recently suggested based on work in a murine model.”
“Of course, it is already clear that we should not intervene too strongly in the birth process. Babies should only be delivered by caesarean section when it is medically necessary,” Wilmes stressed. “We need to be aware that, in doing so, we are apparently intervening massively in the natural interactions between humans and bacteria.”
The study was supported by the Fondation André et Henriette Losch as well as by grants from the ATTRACT, CORE and AFR programs of the Luxembourg National Research Fund (FNR). Additional funds were provided by the University of Luxembourg. Sample collection, processing and storage were co-funded by the Integrated Biobank of Luxembourg under the Personalized Medicine Consortium Diabetes program.

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