A person’s gut microbes may affect whether they develop a fever following vaccination, according to a study published in Science. The results imply that dietary adjustments could help lower these inflammatory reactions, potentially increasing vaccine acceptance and strengthening community immunity.
The research followed 171 healthy adults receiving the SARS-CoV-2 mRNA vaccine, with most participants getting a booster dose. Investigators discovered that individuals whose body temperature rose by at least 0.8°C after vaccination displayed distinct biological indicators beforehand. These included mild intestinal inflammation and gut microbiomes dominated by specific bacteria types.
Participants who developed fever showed higher concentrations of flagellated bacteria from the Lachnospiraceae family, particularly within the Waltera genus. These bacteria generate flagellin proteins, which activate immune sensors like Toll-like receptor 5 (TLR5), prompting inflammation. The family-level association proved stronger than the effect tied solely to Waltera.
To confirm this relationship, the researchers transplanted fecal samples from humans into germ-free mice. Animals receiving microbiota from individuals with raised temperature spikes exhibited stronger immune reactions, including higher levels of the inflammatory signaling molecule interleukin-6 (IL-6). When key receptors in mice, TLR5 and NLRP4, were disabled, the responses weakened but did not disappear entirely.
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Dietary patterns also played a significant role: vegetarians and vegans were less likely to report fever after vaccination. The study further suggested that processed food diets worsened vaccine-related reactions in laboratory models. Stanford University’s Bali Pulendran, PhD, noted that dietary changes could quickly alter gut microbiomes and inflammatory responses, hinting that future interventions might prepare individuals for vaccination as intentionally as vaccine development itself.
Fever and flu-like symptoms frequently follow mRNA-based vaccines, but this work suggests gut microbes, adjustable through diet, may shape these reactions without reducing immune protection. The findings create opportunities for microbiome-focused strategies to limit adverse effects, though additional research is required to develop practical applications.
Beyond vaccination, the study highlights how gut health may influence immune responses to other medical interventions. Pulendran emphasized that understanding these connections could lead to personalized approaches, where dietary or microbial adjustments complement traditional treatments. While challenges remain, the potential to mitigate side effects through modifiable factors offers a promising direction for future medicine.
