Fig. 1: Prenatal transmission of microbes, microbial DNA and metabolites, highlighting “what” can be transferred and the other parameters of the 4 W framework.

Different microbes colonize the mother at multiple body sites, although the focus is on gut bacteria here. Microbially derived metabolites (what) can translocate from the mother gut (from who) during pregnancy (when) into the intestinal lamina propria and blood circulatory system. Metabolites can also cross via the placenta and affect the developing brain of the fetus (where to). Microbially derived DNA from the parent gut can translocate into circulation, cross via the placenta, and may enter different sites in the fetus, including the gut. Sequencing-based techniques may detect the presence of microbial DNA, even when live microbes are not occurring in the system. Live organisms are not expected to translocate outside the gut or cross the placental barrier into the fetus. Pathogenic microorganisms like L. monocytogenes can translocate from the gut and infect the placenta and fetal brain tissue.