Crucial nuances in understanding (mis)associations between the neonatal microbiome and Cesarean delivery

As rates of Cesarean delivery and common non-communicable disorders (NCDs), such as obesity, metabolic disease, and atopy/asthma, have concomitantly increased in recent decades, investigators have attempted to discern a causal link. One line of research has led to a hypothesis that Cesarean birth disrupts the presumed normal process of colonization of the neonatal microbiome with vaginal microbes, yielding NCDs later in life. However, a direct link between a disrupted microbiota transfer at time of delivery and acute and/or chronic illness in infants born via Cesarean has not been causally established. Microbiota seeding from maternal vaginal or stool sources has been preliminarily evaluated as an intervention designed to compensate for the lack of (or limited) exposure to such sources among Cesarean-delivered neonates. However, to date, clinical trials have yet to show a clear health benefit with neonatal 'vaginal seeding' practices. Until the long-term effects of these microbiome alterations can be fully determined, it is paramount to conduct parallel meaningful and mechanistic-minded interrogations of the impact of clinically modifiable maternal, nutritional, or environmental exposure on the functional microbiome over the duration of pregnancy and lactation to determine their role in the mitigation of childhood and adult NCDs.