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ORIGINAL RESEARCH article

Front. Microbiol.

Sec. Microorganisms in Vertebrate Digestive Systems

Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1655383

This article is part of the Research TopicRodent Model Organisms: Therapeutic Treatments and Drugs Interaction with the Gut Microbiome, Volume IIView all 6 articles

Immunomodulatory effects of probiotic Lactobacillus brevis ZG2488 on SARS-CoV-2 vaccine responses in mice

Provisionally accepted
Mengshan ChenMengshan Chen1Zhijie CaoZhijie Cao2Yulu ChenYulu Chen2Zhihong RenZhihong Ren2Simin LuSimin Lu3Danna PuDanna Pu1Sihui ZhangSihui Zhang4Gui ZhangGui Zhang5Jing YangJing Yang2Ji PuJi Pu2Jianguo XuJianguo Xu6*
  • 1Nankai University, Tianjin, China
  • 2Chinese Center for Disease Control and Prevention, Beijing, China
  • 3Chinese Academy of Medical Sciences and Peking Union Medical College Institute of Pathogen Biology, Beijing, China
  • 4Peking University School of Public Health, Beijing, China
  • 5Shandong Provincial Hospital, Jinan, China
  • 6Research Center for Reverse Microbial Etiology, Workstation of Academician, Shanxi Medical University, Taiyuan, China

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This study investigates the immunoenhancing effects of the probiotic Lactobacillus brevis ZG2488 on an adenovirus-vectored SARS-CoV-2 vaccine (AdC68-Delta-S) in mice. Results demonstrate that ZG2488 intervention significantly enhances local mucosal humoral immunity in the respiratory tract (increased SARS-CoV-2-specific IgG in bronchoalveolar lavage fluid, BALF) and systemic Th1 cellular immunity (increased IFN-γ secretion by splenocytes). Transcriptomic analysis revealed upregulation of the JAK-STAT signaling pathway, antigen processing and presentation pathways, and pro-inflammatory pathways (IL-17/TNF/NLR/PI3K-Akt), alongside downregulation of hyperinflammation-associated pathways. CIBERSORT analysis showed that ZG2488 reshaped the splenic immune cell composition, increasing memory CD4+ T cells, Th1 cells, and dendritic cells (DCs), while decreasing macrophages, follicular helper T (Tfh) cells, monocytes, and γδ T cells. This study demonstrates that ZG2488 enhances the SARS-CoV-2 vaccine immune response through synergistic multi-mechanistic actions.

Keywords: Lactobacillus brevis1, SARS-CoV-2 vaccine2, probiotics3, Transcriptomic analysis4, Immune cell reshaping5

Received: 30 Jun 2025; Accepted: 10 Sep 2025.

Copyright: © 2025 Chen, Cao, Chen, Ren, Lu, Pu, Zhang, Zhang, Yang, Pu and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Jianguo Xu, xujianguo@icdc.cn

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material