Antibiotic-induced gut microbiome perturbation alters the immune responses to the rabies vaccine

Yupeng Feng¹, Sanne E de Jong², Ana Paula B N Oliveira³, Hady Samaha⁴, Fan Yang², Mengyun Hu², Yanli Wang², Nour Beydoun⁴, Xia Xie², Haibo Zhang², Dmitri Kazmin², Zhuoqing Fang², Jun Zou⁵, Andrew T Gewirtz⁵, Scott D Boyd⁶, Thomas Hagan⁷, Nadine Rouphael⁴, Bali Pulendran⁸

Affiliations

¹ Institute of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510440, China; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
² Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
³ Department of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
⁴ Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.
⁵ Center for Inflammation, Immunity, and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
⁶ Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA; Sean N. Parker Center for Allergy and Immunology Research, Stanford University, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
⁷ Department of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
⁸ Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: bpulend@stanford.edu.

PMID: 40252648
PMCID: PMC12084132 (available on 2026-05-14)
DOI: 10.1016/j.chom.2025.03.015

Antibiotic-induced gut microbiome perturbation alters the immune responses to the rabies vaccine

Yupeng Feng et al. Cell Host Microbe. 2025.

. 2025 May 14;33(5):705-718.e5.

doi: 10.1016/j.chom.2025.03.015. Epub 2025 Apr 18.

Authors

Affiliations

¹ Institute of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510440, China; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
² Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
³ Department of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
⁴ Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA.
⁵ Center for Inflammation, Immunity, and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
⁶ Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA; Sean N. Parker Center for Allergy and Immunology Research, Stanford University, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
⁷ Department of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
⁸ Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: bpulend@stanford.edu.

PMID: 40252648
PMCID: PMC12084132 (available on 2026-05-14)
DOI: 10.1016/j.chom.2025.03.015

Abstract

The gut microbiome plays a crucial role in modulating human immunity. Previously, we reported that antibiotic-induced microbiome perturbation affects influenza vaccine responses, depending on pre-existing immunity levels. Here, we employed a systems biology approach to analyze the impact of antibiotic administration on both primary and secondary immune responses to the rabies vaccine in humans. Antibiotic administration reduced the gut bacterial load, with a long-lasting reduction in commensal diversity. This alteration was associated with reduced rabies-specific humoral responses. Multi-omics profiling revealed that antibiotic administration induced (1) an enhanced pro-inflammatory signature early after vaccination, (2) a shift in the balance of vaccine-specific T-helper 1 (Th1) to T-follicular-helper response toward Th1 phenotype, and (3) profound alterations in metabolites, particularly in secondary bile acids in the blood. By integrating multi-omics datasets, we generated a multiscale, multi-response network that revealed key regulatory nodes, including the microbiota, secondary bile acids, and humoral immunity to vaccination.

Keywords: T cells; antibody; innate immunity; metabolism; microbiome; rabies vaccine; systems biology; systems immunology; systems vaccinology.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

References

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Antibiotic-induced gut microbiome perturbation alters the immune responses to the rabies vaccine

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Antibiotic-induced gut microbiome perturbation alters the immune responses to the rabies vaccine

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