The human gut microbiome primes fever after vaccination
Fever is a common adverse reaction to vaccination, contributing to vaccine hesitancy and reduced uptake. To understand variation in fever risk, we longitudinally profiled fecal microbiota, oral temperature, and serological markers in 171 healthy adults receiving Severe acute respiratory syndrome coronavirus 2 mRNA vaccines. Fever risk correlated with low-grade intestinal inflammation, increased abundance of flagellated Lachnospiraceae bacteria, and increased flagellin expression prevaccine. Microbiomes from fever-high donors triggered stronger inflammation in human intestinal organoids and drove flagellin-dependent vaccine reactions in gnotobiotic mice. Moreover, microbiome flagellin phenotypes and murine vaccine reactions were modifiable by diet. Consistent with this, human fever risk was associated with self-reported diet and metabolic markers. These findings identify the gut microbiome as a driver of vaccine-induced fever, suggesting that microbiome-targeting strategies could modulate immune tone and improve vaccine side effects.
Authors
- Marc‐André Langlois (ORCID: https://orcid.org/0000-0003-4652-3029)
- Dennis Jakob (ORCID: https://orcid.org/0000-0001-5084-4859)
- Benoît Chassaing (ORCID: https://orcid.org/0000-0002-4285-769X)
- Andrew T. Gewirtz (ORCID: https://orcid.org/0000-0002-6338-7578)
- Meral Esen (ORCID: https://orcid.org/0000-0001-8638-4719)
- Peter G. Kremsner (ORCID: https://orcid.org/0000-0002-3926-4113)
- Wim Alexander Fleischmann (ORCID: https://orcid.org/0000-0002-2480-0614)
- Ruth E. Ley (ORCID: https://orcid.org/0000-0002-9087-1672)
- Lisa Maier (ORCID: https://orcid.org/0000-0002-6473-4762)
- Judith Flügge
- Johanna Marika Gaile
- Roberta Allgayer de Moraes
- Carolin Wilhelm
- Alex S. Siebner (ORCID: https://orcid.org/0009-0008-7412-8943)
- Alina Prokipchuk
- E. ; https://orcid.org/0000-0003-0208-4095 Atay
- K. ; https://orcid.org/0000-0002-7580-1924 Huus
- Y. ; https://orcid.org/0000-0002-2461-1901 Tan
- N. ; https://orcid.org/0000-0002-7424-5276 Youngblut
- S. Dauser
- D. ; https://orcid.org/0000-0002-1559-1531 Vu
- J. Parsonnet
- µHEAT Clinical Study Group
- H. Abo
- M. Azad
- R. Knight
- R. Liu
- A. Ke
- H. Rytter
- S. Kang
- R. Keller
- L. Lotoski
- A. ; https://orcid.org/0000-0002-7358-2537 Tyakht
- Geerten Smeenk (ORCID: https://orcid.org/0009-0008-4662-4018)
- Julian J. Gabor
Institutions
- University of Ottawa (CA)
- Institut Pasteur (FR)
- Georgia State University (US)
- Hong Kong University of Science and Technology (HK)
- Université Paris Cité (FR)
- Centre de Recherche Médicales de Lambaréné (GA)
- German Center for Infection Research (DE)
- La Jolla Bioengineering Institute (US)
- Max Planck Institute for Biology (DE)
- University of Manitoba (CA)
- University of Tübingen (DE)
- Ottawa University (US)
- Stanford University (US)
Publication Details
- Journal
- Science
- Published
- 2026-10-08
- DOI
- https://doi.org/10.1126/science.aea7733
- Citations
- 1
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 1.94