Maternal and neonatal viromes indicate the risk of offspring's gastrointestinal tract exposure to pathogenic viruses of vaginal origin during delivery.

A cumulative effect of enterovirus and gluten intake on the risk of celiac disease autoimmunity in infants highlights the significance of viral exposure in early life on the health of children. However, pathogenic viruses may be transmitted to the offspring in an earlier period, raising the possibility that women whose vaginas are inhabited by such viruses may have had their babies infected as early as the time of delivery. A high-resolution intergenerational virome atlas was obtained by metagenomic sequencing and virome analysis on 486 samples from six body sites of 99 mother-neonate pairs. We found that neonates had less diverse oral and enteric viruses than mothers. Vaginally delivered newborns seconds after birth had a more similar oral virome and more viruses of vaginal origin than cesarean-section (C-section) newborns (56.9% vs. 5.8%). Such viruses include both Lactobacillus phage and potentially pathogenic viruses, such as herpesvirus, vaccinia virus, and hepacivirus, illustrating a relatively high variety of the pioneer viral taxa at the time of delivery and a delivery-dependent mother-to-neonate transmission along the vaginal-oral-intestinal route. Neonates are exposed to vaginal viruses as they pass through the reproductive tract, and viruses of vaginal origin may threaten their health. These findings challenge the conventional notion that vaginal delivery is definitely better than cesarean delivery from the perspective of microbial transmission. Screening for vaginal virome before delivery is a worthwhile step to advocate in normal labor to eliminate the risk of intergenerational transmission of pathogenic viruses to offspring.