Study Explores How Gut Bacteria May Intensify Vaccine-Related Inflammation - Video

A person's gut microbiome may influence whether they develop a fever after vaccination, according to a new study. The findings suggest that targeting gut bacteria and potentially modifying diet could one day help reduce vaccine-related inflammation without compromising the immune protection vaccines provide.

Vaccines are essential for preventing infectious diseases, but people experience different immune responses and side effects. Fever and flu-like symptoms are common reactions, particularly following mRNA and lipid nanoparticle-based vaccines. These symptoms may discourage people from receiving future doses, contributing to vaccine hesitancy. However, the biological factors responsible for differences in vaccine-related fever remain poorly understood.

To investigate this, researchers led by Kelsey Huus examined the gut microbiomes, body temperatures and blood-based immune markers of 171 healthy adults before and after they received an mRNA vaccine against SARS-CoV-2, the virus responsible for COVID-19.

The findings suggested that certain gut bacteria, particularly members of the Lachnospiraceae family, produce flagellin, a protein that can activate inflammatory immune pathways. Participants with greater intestinal inflammation or higher levels of flagellin expression before vaccination were more likely to develop a fever following vaccination.

The researchers also identified associations between dietary patterns and microbiome activity. Furthermore, dietary manipulation altered microbiome composition and associated vaccine responses, suggesting that diet may influence vaccine-related inflammation.

Importantly, the researchers found that flagellin, inflammation and dietary factors did not appear to affect antibody responses, suggesting that increased inflammatory reactions did not necessarily translate into changes in vaccine-induced immunity.

The findings highlight the potential role of the gut microbiome in individual vaccine responses. However, further research is needed to establish whether dietary interventions can reliably reduce vaccine-related fever while preserving protection against infections.

REFERENCE: Huus, K. E., et al. (2026). The human gut microbiome primes fever after vaccination. Science. DOI: 10.1126/science.aea7733