Antibiotic Treatment during Gestation Enhances Susceptibility to Mycobacterium tuberculosis in Offspring

Whether antibiotic treatment during gestation impacts T cell immunity to vaccination in offspring is unexplored. Dams treated with polymyxin B (PMB) during gestation (Mg) displayed altered microbial communities prior to delivery compared to control dams (Mc). Differences in microbiota were also evident in pups born to polymyxin B-treated dams (Pg) compared to control pups (Pc). When pups were immunized with Bacille Calmette-Guerin (BCG), we observed no difference in TB10.4-specific T cells between Pc and Pg 4 weeks postimmunization. Significantly fewer splenic CD4 T cells from BCG-vaccinated Pg produced interleukin-2 (IL-2) upon stimulation, suggesting a possible functional deficiency. There was no difference in purified protein derivative (PPD)-specific IgG between Pc and Pg at this time point. However, when infected with Mycobacterium tuberculosis, Pg displayed significantly higher bacterial burden in the lung than Pc. Our results show that maternal PMB treatment during gestation may not impact splenic antigen-specific T cell responses following BCG vaccination but alters susceptibility to M. tuberculosis in offspring. The composition of the pioneer microbiota that colonize the infant gut are determined by the mother. Polymyxin B-induced changes in the maternal microbiota during pregnancy impact the offspring gut microbiota but not vaccine-specific CD4 T cell response. However, when infected with Mycobacterium tuberculosis, offspring born to mothers with an altered gut microbiota are susceptible to infection compared to those born to mothers not exposed to antibiotics.