Antibiotic exposure in children has been associated with the risk of inflammatory bowel disease (IBD). Antibiotic use in children or in their pregnant mother can affect how the intestinal microbiome develops, so 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 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 developed markedly increased colitis. Taken together, our findings indicate that antibiotic exposure shaping the maternal gut microbiota has effects that extend to the offspring, with both ecological and long-term disease consequences.
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The authors thank M. Bower and the National Gnotobiotic Rodent Resource Center, University of North Carolina, Chapel Hill, for supplying mice, the NYUMC Genome Technology Center for help with sequencing (partially supported by a Cancer Center Support grant, P30CA016087, at the Laura and Isaac Perlmutter Cancer Center) and the NYUMC Histology Core for assistance preparing samples for histology. These studies were supported by NIH grants DK090989, OD010995 and DK034987 and the Crohn’s and Colitis Foundation of America, by the Ziff Family, Knapp Family and C&D funds, the Judith & Stewart Colton Center for Autoimmunity, and the Diane Belfer Program for Human Microbial Ecology.
The authors declare no competing financial interests.
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Schulfer, A.F., Battaglia, T., Alvarez, Y. et al. Intergenerational transfer of antibiotic-perturbed microbiota enhances colitis in susceptible mice. Nat Microbiol 3, 234–242 (2018). https://doi.org/10.1038/s41564-017-0075-5
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