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 L. Ho,
Yue Sandra Yin,
Xiaozhou Zhang,
Ekaterina Novikova,
Katelyn Jackson,
Briana J. Mullins,
Victoria E. Ruiz,
Marcus J. Hines,
Xue-Song Zhang,
Anne Müller,
Sergei B. Koralov,
Martin J. Blaser
Affiliations
Timothy C. Borbet
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
Miranda B. Pawline
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
Jackie Li
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
Melody L. Ho
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
Yue Sandra Yin
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Center for Advanced Biotechnology and Medicine, Rutgers University, New Brunswick, NJ 08854, USA
Xiaozhou Zhang
Institute of Molecular Cancer Research, University of Zurich, Zurich 8057, Switzerland
Ekaterina Novikova
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
Katelyn Jackson
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Department of Biological Sciences, Mississippi State University, Mississippi State, MS 39762, USA
Briana J. Mullins
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
Victoria E. Ruiz
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
Marcus J. Hines
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
Xue-Song Zhang
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Center for Advanced Biotechnology and Medicine, Rutgers University, New Brunswick, NJ 08854, USA
Anne Müller
Institute of Molecular Cancer Research, University of Zurich, Zurich 8057, Switzerland
Sergei B. Koralov
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Corresponding author
Martin J. Blaser
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Center for Advanced Biotechnology and Medicine, Rutgers University, New Brunswick, NJ 08854, USA; Corresponding author
Summary: 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.
