Science (New York, N.Y.)Oct 8, 2026

The human gut microbiome may prepare the body to develop fever after vaccination

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 9, 2026

Abstract

Fever risk after vaccination is correlated with low-grade intestinal inflammation and changes in gut bacteria in 171 healthy adults.

Low-grade intestinal inflammation is associated with an increased risk of fever following vaccination.
Higher levels of flagellated Lachnospiraceae bacteria may contribute to elevated fever risk.
Increased expression of flagellin before vaccination correlates with a higher incidence of fever.
Fecal microbiota from individuals who experienced high fever elicited stronger inflammatory responses in human intestinal organoids.
Dietary changes can modify microbiome flagellin phenotypes and influence vaccine reactions in mice.
Self-reported dietary habits and metabolic markers are linked to fever risk in humans.

Simplified

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.

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Your gut microbiome may predict whether you'll get a fever after an mRNA vaccine

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The human gut microbiome may prepare the body to develop fever after vaccination

Abstract

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