Certain gut bacteria may intensify inflammatory responses to vaccines

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

Vaccines are a crucial tool for ensuring public health, but people vary widely in their immune responses and side effects. Fever and flu-like symptoms are among the most common adverse reactions to vaccines, particularly mRNA- and lipid nanoparticle-based vaccines. These reactions can discourage future vaccination and contribute to vaccine hesitancy and mistrust. However, not all those who receive a vaccination develop a fever and those who do tend to get a fever across repeated doses, suggesting the importance of individual risk factors for fever. The reasons for this variation are not well understood.

In this study, Kelsey Huus and colleagues speculated that the gut microbiome, which is known to influence immune activity, may play a role in driving these reactions. To test this hypothesis, Huus et al. profiled the fecal microbiomes, body temperature, and blood-based immune markers of 171 healthy adults before and after receiving the mRNA vaccination for SARS-CoV-2. The findings showed that certain gut bacteria, especially Lachnospiraceae, produce flagellin, which can activate inflammatory immune pathways and intensify vaccine-related reactions. Those who had greater pre-vaccination intestinal inflammation or higher levels of flagellin expression in the gut tended to develop vaccine-induced fever. What's more, the authors found that industrialized diets may promote this inflammatory activity.

Vegetarian diets tended to correlate with microbiome features that contributed to less fever, while lower consumption of whole plant foods and diets characterized by greater fat or processed-food intake were associated with the inflammatory, fever-associated microbiome. Dietary manipulation altered both microbiome compositions and their associated vaccine responses. Importantly, Huus et al. show that flagellin, inflammation, and diet do not affect antibody responses to vaccines, suggesting that the microbiome-driven inflammation increased vaccine side effects without necessarily affecting immunity. "Diet, microbial ecology, and the metabolic state are not immutable, and people might one day prepare for vaccination as deliberately as the vaccine itself is formulated," writes Bali Pulendran in a related Perspective.