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bioRxiv · 10.64898/2025.12.08.692990

Effect of Perinatal Ampicillin or Amoxicillin/Clavulanate Exposure on Maternal and Infant Gut Microbiome, Metabolome, and Infant Responses to the 20-valent Pneumococcal Conjugate Vaccine

Suzuki, E.·Deleray, V.·Zemlin, J.·Kousha, A.·Nonoguchi, H.·Sun, D.·Tsai, C.-M.·Zuffa, S.·Kvitne, K. E.·Dorrestein, P. C.·Tsunoda, S. M.·Nizet, V.·Liu, G. Y.·Askarian, F.
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Abstract

Emerging studies suggest that antibiotics can disrupt the gut microbiome and alter vaccine-induced immune responses, but the specific consequences of early-life exposure on neonatal immune development remains poorly understood. Here, we examined how two antibiotics frequently used in perinatal care, broad-spectrum ampicillin (AMP) and the extended-spectrum combination amoxicillin/clavulanate (AMOX/CLAV), administered during gestation and lactation, influence neonatal gut microbiome composition, fecal metabolome profiles, and responses to the 20-valent pneumococcal conjugate vaccine (PCV20). Maternal treatment with AMOX/CLAV, but not AMP, significantly reduced PCV-specific IgG titers at 4-and 6-weeks post-prime immunization compared to untreated controls. Exclusive exposure to AMOX/CLAV also impaired neutrophil-mediated opsonophagocytic killing, indicating diminished antibody functionality. These effects were transient, with immune parameters normalizing by week 8 post-prime immunization. Metabolomic and microbiome profiling revealed that maternal AMP and AMOX/CLAV differentially perturbed specific metabolite classes including bile acids, N-acyl lipids, and indole-derivatives, as well as key commensal taxa including Bacteroidales and Coriobacteriales within the gut microbiota. Together, these findings reveal a previously underappreciated maternal-offspring route of antibiotic influence that transiently disrupts neonatal vaccine responsiveness through microbiome and metabolome alterations. These results highlight maternal antibiotic exposure as a modifiable factor shaping early-life immunity.

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Suzuki, E., Deleray, V., Zemlin, J., Kousha, A., Nonoguchi, H., Sun, D., Tsai, C.-M., Zuffa, S., Kvitne, K. E., Dorrestein, P. C., Tsunoda, S. M., Nizet, V., Liu, G. Y., Askarian, F.. 2025-12-08. Effect of Perinatal Ampicillin or Amoxicillin/Clavulanate Exposure on Maternal and Infant Gut Microbiome, Metabolome, and Infant Responses to the 20-valent Pneumococcal Conjugate Vaccine. https://doi.org/10.64898/2025.12.08.692990

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