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

Antibiotics have long-lasting consequences on the gut microbiota with the potential to impact host physiology and health. Antibiotic exposure has been associated with increased IBD risk- notable since antibiotics are massively used worldwide. Antibiotic use is extensive during pregnancy, however, little is known about the transgenerational impact of an antibiotic-perturbed microbiota. Because of the potential importance of intergenerational microbiota transmission, we hypothesized that a maternally inherited antibiotic-perturbed microbiota affects the risk of experimental colitis in offspring. Here we demonstrate that 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 mice and wild type mice, we showed that both inoculum and genotype shape the microbiota populations in the offspring. Because 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 had markedly increased risk of 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.