tetano
Editor, Senior Moderator
Science
. 2026 Oct 8;394(6820):eaea7733.
doi: 10.1126/science.aea7733. Epub 2026 Oct 8.
Kelsey E Huus 1 2 ; µHEAT Study Group‡; Hirohito Abo 3 , Yi Han Tan 1 2 , Ezgi Atay 1 2 , Héloïse Rytter 4 , Ronald Keller 1 2 , Silke Dauser 1 2 , Dai Long Vu 5 , Meghan B Azad 6 , Rob Knight 7 8 , Alfred Ke 6 , Larisa Lotoski 6 , Marc-André Langlois 9 , Rong Liu 3 , Alexander V Tyakht 1 2 , Nicholas Youngblut 1 2 , Sang-Moo Kang 3 , Julie Parsonnet 10 , Lisa Maier 2 11 , Benoit Chassaing 4 , Peter G Kremsner 2 12 13 14 , Andrew T Gewirtz 3 , Meral Esen 2 3 13 , Ruth E Ley 1 2 , Julian J Gabor 2 11 , Johanna M Gaile 2 11 , Wim A Fleischmann 2 11 , Alex S Siebner 2 11 , Geerten Smeenk 2 11 , Judith Flügge 2 11 , Roberta Allgayer De Moraes 2 11 , Dennis Jakob 5 , Alina Prokipchuk 1 2 , Carolin Wilhelm 1 2
Affiliations Expand
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.
. 2026 Oct 8;394(6820):eaea7733.
doi: 10.1126/science.aea7733. Epub 2026 Oct 8.
The human gut microbiome primes fever after vaccination
Kelsey E Huus 1 2 ; µHEAT Study Group‡; Hirohito Abo 3 , Yi Han Tan 1 2 , Ezgi Atay 1 2 , Héloïse Rytter 4 , Ronald Keller 1 2 , Silke Dauser 1 2 , Dai Long Vu 5 , Meghan B Azad 6 , Rob Knight 7 8 , Alfred Ke 6 , Larisa Lotoski 6 , Marc-André Langlois 9 , Rong Liu 3 , Alexander V Tyakht 1 2 , Nicholas Youngblut 1 2 , Sang-Moo Kang 3 , Julie Parsonnet 10 , Lisa Maier 2 11 , Benoit Chassaing 4 , Peter G Kremsner 2 12 13 14 , Andrew T Gewirtz 3 , Meral Esen 2 3 13 , Ruth E Ley 1 2 , Julian J Gabor 2 11 , Johanna M Gaile 2 11 , Wim A Fleischmann 2 11 , Alex S Siebner 2 11 , Geerten Smeenk 2 11 , Judith Flügge 2 11 , Roberta Allgayer De Moraes 2 11 , Dennis Jakob 5 , Alina Prokipchuk 1 2 , Carolin Wilhelm 1 2
Affiliations Expand
- PMID: 42848888
- DOI: 10.1126/science.aea7733
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.