Delivery mode impacts gut bacteriophage colonization during infancy.

Cesarean section delivery is associated with altered early-life bacterial colonization and later adverse inflammatory outcomes. Although gut bacteriophages can alter the gut microbiome and host responses, little is known about how delivery mode impacts bacteriophage colonization over time. Therefore, we conducted shotgun metagenomic sequencing on serial stool samples from infants from birth to 24 months of age. 60% of infants were born by vaginal delivery. 94% of the DNA viral sequences identified were bacteriophages. Virome alpha diversity was increased in vaginally delivered infants at 2 months (p=0.004). Beta diversity differed by delivery mode up to 12 months when stratified by peripartum antibiotic use (p<0.05). Predicted bacteriophage hosts differed by delivery mode (Q <0.1) up to 24 months. Moreover, predicted bacteriophage functional genes differed by delivery mode up to 24 months. There was a higher abundance of viral auxiliary metabolic genes associated with host responses in vaginal delivery at early timepoints. Clear differences in bacteriophage composition and function by delivery mode were seen in early life. Given that bacteriophages are known to affect immune responses, our results suggest that future investigation into how delivery mode leads to adverse inflammatory outcomes should also include the potential role of bacteriophages and transkingdom interactions.