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

doi:10.1016/j.isci.2023.106810

Disruption of the early-life microbiota alters Peyer's patch development and germinal center formation in gastrointestinal-associated lymphoid tissue

iScience. 2023 May 4;26(6):106810. doi: 10.1016/j.isci.2023.106810. eCollection 2023 Jun 16.

Authors

Timothy C Borbet¹, Miranda B Pawline¹, Jackie Li¹, Melody L Ho¹, Yue Sandra Yin^{1

2}, Xiaozhou Zhang³, Ekaterina Novikova¹, Katelyn Jackson^{1

4}, Briana J Mullins¹, Victoria E Ruiz¹, Marcus J Hines¹, Xue-Song Zhang^{1

2}, Anne Müller³, Sergei B Koralov¹, Martin J Blaser^{1

2}

Affiliations

¹ Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
² Center for Advanced Biotechnology and Medicine, Rutgers University, New Brunswick, NJ 08854, USA.
³ Institute of Molecular Cancer Research, University of Zurich, Zurich 8057, Switzerland.
⁴ Department of Biological Sciences, Mississippi State University, Mississippi State, MS 39762, USA.

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.

Keywords: Developmental biology; Microbiology.