Disruption of the early-life microbiota alters Peyer’s patch development and germinal center formation in gastrointestinal-associated lymphoid tissue
Timothy C. Borbet, Miranda B. Pawline, Jackie Li, Melody Ho, Yue Yin, Xiaozhou Zhang, Е. S. Novikova, Katelyn Jackson, Briana J. Mullins, Victoria E. Ruiz, Marcus J. Hines, Xue‐Song Zhang, Anne Müller, Sergei B. Koralov, Martin J. Blaser
Abstract
During postnatal development, both the maturing microbiome and the host immune system are susceptible to environmental perturbations such as antibiotic use. The impact of timing in which antibiotic exposure occurs was investigated by treating mice from days 5–9 with amoxicillin or azithromycin, two of the most commonly prescribed medications in children. Both early-life antibiotic regimens disrupted Peyer's patch development and immune cell abundance, with a sustained decrease in germinal center formation and diminished intestinal immunoglobulin A (IgA) production. These effects were less pronounced in adult mice. Through comparative analysis of microbial taxa, Bifidobacterium longum abundance was found to be associated with germinal center frequency. When re-introduced to antibiotic-exposed mice, B . longum partially rescued the immunological deficits. These findings suggest that early-life antibiotic use affects the development of intestinal IgA-producing B cell functions and that probiotic strains could be used to restore normal development after antibiotic exposure.