Intergenerational transfer of antibiotic-perturbed microbiota enhances colitis in susceptible mice

Abstract

Antibiotic exposure in children has been associated with the risk of Inflammatory Bowel Disease (IBD). Since antibiotic use in children or in their pregnant mother can affect how the intestinal microbiome develops, we asked whether the transfer of an antibiotic-perturbed microbiota from mothers to their children could affect their risk of developing IBD. Here we demonstrate that germ-free adult pregnant mice inoculated with a gut microbial community shaped by antibiotic exposure transmitted their perturbed microbiota to their offspring with high fidelity. Without any direct or continued exposure to antibiotics, this dysbiotic microbiota in the offspring remained distinct from controls for at least 21 weeks. By using both IL-10-deficient and wild type mothers, we showed that both inoculum and genotype shape the microbiota populations in the offspring. Since IL10−/− mice are genetically susceptible to colitis, we could assess the risk due to maternal transmission of an antibiotic-perturbed microbiota. We found that the IL10−/− offspring that had received the perturbed gut microbiota developed markedly increased colitis. Taken together, our findings indicate that antibiotic exposure shaping the maternal gut microbiota has effects that extend to their offspring with both ecological and long-term disease consequences.