Babies born by C-section aren’t exposed to maternal vaginal microbes during birth, and previous studies have linked C-section birth with a higher risk of developmental problems. Now, researchers have found that microbes transferred during vaginal birth may produce compounds that can cross the skin barrier and reach the brain, supporting brain development.

The findings, published in Cell Host & Microbe, suggest that restoring missing maternal microbes after C-section birth could be a new strategy to support early neurodevelopment.

C-section birth has been associated with developmental deficits, but the reasons remain unclear. Although most explanations have focused on the gut microbiota, little is known about the role a newborn’s skin bacteria.

Researchers led by Hao Liu at Southern Medical University in Guangzhou, China, tested whether vaginal microbiota transfer, in which maternal vaginal fluids are applied to a newborn’s skin after C-section birth, could restore helpful microbes and support early development.

Skin bacteria

Applying maternal vaginal fluids to infants born by C-section changed the babies’ skin microbiota so that it more closely resembled that of vaginally delivered infants. Two bacterial species, Lactobacillus crispatus and Bacteroides fragilis, became especially enriched. 

In mice, applying maternal vaginal fluids to the skin of pups born by C-section improved early motor development, while oral treatment did not. The researchers discovered a previously unknown fatty molecule called N-bc2S1P on newborn skin. This molecule appears to be made by two types of bacteria, and higher levels were associated with better developmental outcomes in both babies and mice. 

In newborn mice, N-bc2S1P applied to the skin entered the bloodstream and then the brain, where it accumulated in the hippocampus—a region involved in learning and memory.

Engineered microbe

In the brain, N-bc2S1P increased the activity of genes involved in a signalling pathway that helps guide brain cell growth and maturation. These changes improved early motor behavior, but the effects faded after the molecule disappeared from the brain.

So, the researchers genetically engineered a common skin bacterium, Staphylococcus epidermidis, to continuously make N-bc2S1P on the skin of mice. Animals with the engineered bacterium showed improvements in movement, learning and memory, as well as anxiety-related behavior compared with untreated mice born by C-section.

“Together, these findings define a mother-to-infant lipid metabolic circuit and highlight probiotic metabolic engineering as a tractable, potential strategy to mitigate neurodevelopmental risks associated with [C-secton],” the authros say.