Perinatal Antibiotic Prophylaxis - Friend or Foe?

Nearly half of all pregnant women receive prophylactic antibiotics prior to delivery for the prevention of neonatal early onset sepsis and maternal surgical site infection. Studies have shown that oral antibiotics administered to infants alter the microbiota resulting in increased obesity, allergy, asthma, and neurobehavioral problems. Little research has focused, however, on the impact of the prophylactic antibiotics given to mothers prior to delivery, which are typically parenteral and of limited duration. Here we use a murine model to investigate the effects of antepartum antibiotic administration on the microbiota of C57Bl/6 pregnant dams and their offspring. After receiving 1-3 doses of antibiotics in the last days of gestation, dams had markedly reduced fecal alpha diversity with a notable reduction of species in the Bacteroidetes phylum, while species in the Firmicutes phylum increased. Offspring of exposed mice had reduced bacterial diversity and altered colonization in tested gastrointestinal compartments into maturity. Metagenomic analysis revealed that genes encoding protein functional units remained altered in female adult offspring of exposed dams. Female offspring had increased obesity, decreased glucose tolerance, and insulin insensitivity if their dams had antibiotics prior to delivery. Both males and females had increased liver steatosis and low-grade focal liver inflammation. There was no change in intestinal gene expression in response to altered bacterial colonization, but significant up-regulation in intestinal heat shock proteins in response to the western diet. Exposure to prophylactic antibiotics prior to delivery decreases the diversity of offspring microbiota reducing microbial genetic resiliency to stressors such as those imposed by the western diet thus allowing colonization with microbes that predispose offspring to glucose intolerance and obesity.