The human gut microbiome primes fever after vaccination
(1) Huus KE (2) Abo H (3) Tan YH (4) Atay E (5) Rytter H (6) Keller R (7) Dauser S (8) Vu DL (9) Azad MB (10) Knight R (11) Ke A (12) Lotoski L (13) Langlois MA (14) Liu R (15) Tyakht AV (16) Youngblut N (17) Kang SM (18) Parsonnet J (19) Maier L (20) Chassaing B (21) Kremsner PG (22) Gewirtz AT (23) Esen M (24) Ley RE
Huus et al. studied the impact of the SARS-CoV-2 mRNA vaccine on the gut microbiome–immune axis in 171 healthy volunteers. Participants with temperatures ≥ 0.8ºC above personal baseline upon vaccination demonstrated chronic low-grade intestinal inflammation, high expression of flagellin, and abundance of flagellated bacteria. In mice, the microbiome from these participants drove innate immune detection of flagellin by TLR5 and NLRC4, and vaccine-induced adverse reactions. Western diet and common food additives boosted the abundance of flagellated bacteria and microbial flagellin production in vitro and in vivo.
Contributed by Ute Burkhardt
(1) Huus KE (2) Abo H (3) Tan YH (4) Atay E (5) Rytter H (6) Keller R (7) Dauser S (8) Vu DL (9) Azad MB (10) Knight R (11) Ke A (12) Lotoski L (13) Langlois MA (14) Liu R (15) Tyakht AV (16) Youngblut N (17) Kang SM (18) Parsonnet J (19) Maier L (20) Chassaing B (21) Kremsner PG (22) Gewirtz AT (23) Esen M (24) Ley RE
Huus et al. studied the impact of the SARS-CoV-2 mRNA vaccine on the gut microbiome–immune axis in 171 healthy volunteers. Participants with temperatures ≥ 0.8ºC above personal baseline upon vaccination demonstrated chronic low-grade intestinal inflammation, high expression of flagellin, and abundance of flagellated bacteria. In mice, the microbiome from these participants drove innate immune detection of flagellin by TLR5 and NLRC4, and vaccine-induced adverse reactions. Western diet and common food additives boosted the abundance of flagellated bacteria and microbial flagellin production in vitro and in vivo.
Contributed by Ute Burkhardt
ABSTRACT: 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.
Author Info:
(1) Department of Microbiome Science, Max Planck Institute for Biology, Tbingen, Germany. Controlling Microbes to Fight Infections (CMFI) Cluster of Excellence, Tbingen, Germany.
(2) Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. (3) Department of Microbiome Science, Max Planck Institute for Biology, Tbingen, Germany. Controlling Microbes to Fight Infections (CMFI) Cluster of Excellence, Tbingen, Germany. (4) Department of Microbiome Science, Max Planck Institute for Biology, Tbingen, Germany. Controlling Microbes to Fight Infections (CMFI) Cluster of Excellence, Tbingen, Germany. (5) Microbiome-Host Interactions, Institut Pasteur, Universit Paris Cit, Paris, France. (6) Department of Microbiome Science, Max Planck Institute for Biology, Tbingen, Germany. Controlling Microbes to Fight Infections (CMFI) Cluster of Excellence, Tbingen, Germany. (7) Department of Microbiome Science, Max Planck Institute for Biology, Tbingen, Germany. Controlling Microbes to Fight Infections (CMFI) Cluster of Excellence, Tbingen, Germany. (8) Mass Spectrometry Facility, Max Planck Institute for Biology Tbingen, Tbingen, Germany. (9) Department of Pediatrics and Child Health, University of Manitoba, Manitoba, Canada. (10) Department of Pediatrics; Center for Microbiome Innovation; Department of Computer Science and Engineering; Shu Chien-Gene Lay Department of Bioengineering; Halõcõo_lu Data Science Institute, University of California San Diego, La Jolla, CA, USA. Hong Kong University of Science and Technology Jockey Club Institute for Advanced Study, Hong Kong University of Science and Technology, Hong Kong SAR, China. (11) Department of Pediatrics and Child Health, University of Manitoba, Manitoba, Canada. (12) Department of Pediatrics and Child Health, University of Manitoba, Manitoba, Canada. (13) Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, OT, Canada. (14) Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. (15) Department of Microbiome Science, Max Planck Institute for Biology, Tbingen, Germany. Controlling Microbes to Fight Infections (CMFI) Cluster of Excellence, Tbingen, Germany. (16) Department of Microbiome Science, Max Planck Institute for Biology, Tbingen, Germany. Controlling Microbes to Fight Infections (CMFI) Cluster of Excellence, Tbingen, Germany. (17) Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. (18) Departments of Medicine and of Epidemiology and Population Health, Stanford University, Stanford, CA, USA. (19) Controlling Microbes to Fight Infections (CMFI) Cluster of Excellence, Tbingen, Germany. Institute for Tropical Medicine, University of Tbingen, Tbingen, Germany. (20) Microbiome-Host Interactions, Institut Pasteur, Universit Paris Cit, Paris, France. (21) Controlling Microbes to Fight Infections (CMFI) Cluster of Excellence, Tbingen, Germany. Interfaculty Institute of Microbiology and Infection Medicine, University of Tbingen, Tbingen, Germany. Centre de Recherches Medicales de Lambarn, Lambarn, Gabon. German Center for Infection Research (DZIF), partner site Tbingen, Tbingen, Germany. (22) Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. (23) Controlling Microbes to Fight Infections (CMFI) Cluster of Excellence, Tbingen, Germany. Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. Centre de Recherches Medicales de Lambarn, Lambarn, Gabon. (24) Department of Microbiome Science, Max Planck Institute for Biology, Tbingen, Germany. Controlling Microbes to Fight Infections (CMFI) Cluster of Excellence, Tbingen, Germany.
Citation: Science 2026 Oct 8 394:eaea7733 Epub10/08/2026
