Vaccine-induced fevers are associated with flagellar activity of the gut microbiome

Kelsey Huus

Max Planck Institute for Biology Tübingen, Department of Microbiome Sciences, Max Planck Ring 5, 72076 Tübingen [DE], kelsey.huus@tuebingen.mpg.de

Author(s): Kelsey Huus, Ruth Ley

The intestinal microbiota modulates host immune responses, with consequences for infectious diseases and for vaccine efficacy. However, data on microbiome-immune interactions in healthy humans remains limited, particularly in the context of innate immunity. To study interactions between the healthy human microbiota and a sterile immune response, we established the µHEAT (Microbial-Human Ecology And Temperature) study, which longitudinally profiled the fecal microbiota, oral body temperature and serum antibody responses of 179 healthy adults (18-40 years old) before and after vaccination for SARS-CoV-2. We hypothesized the human gut microbiome would modulate innate fever responses to vaccination. We found that vaccine-induced fevers were individualized and correlated with prior fever episodes, suggesting that certain people are more ‘fever-prone’. Such participants had higher baseline markers of systemic inflammation and higher intestinal inflammation following the vaccine. Moreover, the baseline gut microbiome of individuals with fever displayed a stable and striking upregulation of flagellin gene expression, and an enrichment in flagellated Lachnospiraceae species. Although causality remains to be established, we speculate that flagellin - a known ligand of innate immune receptors - may act as a natural adjuvant to stimulate fever. Together, these data improve our understanding of human immune-microbiome interactions, with implications for vaccine development.

 

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