- Researchers found differences in the gut microbiome before vaccination that were associated with whether people subsequently developed a stronger fever response.
- Transferring gut microbes from participants into germ-free mice produced similar differences in inflammation, strengthening the case for a biological effect.
- The human diet findings were observational, and there is no evidence yet that changing diet, taking probiotics or altering the microbiome will prevent vaccine side effects.
The trillions of microorganisms living in the gut may help explain why one person develops a fever after a vaccination while another feels almost nothing.
Researchers have found that people who developed stronger fever responses after COVID-19 vaccination already had measurable differences in their gut microbiome before receiving the vaccine.
The study, published in Science, involved 171 healthy adults receiving SARS-CoV-2 mRNA vaccines.
Participants provided stool samples for microbiome analysis and blood samples for immune measurements, while recording their temperatures before and after vaccination.
The researchers found that people who subsequently experienced stronger fever responses had greater activity in bacterial genes involved in producing flagella – whip-like structures that certain bacteria use to move.
Flagella contain proteins called flagellins.
The immune system can recognise flagellin as a potential danger signal, triggering inflammation.
Importantly, the microbiome differences were present before the vaccine was given, alongside evidence of a more inflammatory baseline state.
Researchers then tested the idea in mice
Observational findings in humans cannot on their own establish that the gut bacteria caused the stronger inflammatory response.
The researchers therefore carried out additional experiments.
Gut microbiomes from human participants were transferred into mice raised without their own intestinal microbes.
Mice receiving microbes from people who had experienced stronger fever responses subsequently developed more inflammation after vaccination than mice receiving microbiomes from participants with milder responses.
The effect was partly dependent on the animals’ ability to detect bacterial flagellin.
Researchers also tested the microbes in human intestinal organoids.
Together, the experiments provide stronger mechanistic evidence that gut bacteria can influence the inflammatory state of the immune system.
That does not mean exactly the same mechanism has been proven to cause fever in every vaccinated person.
Could diet change the response?
This is where the findings need particularly careful interpretation.
People reporting more plant-based diets tended to have weaker fever responses.
In laboratory experiments, certain food additives increased bacterial flagellin production, while a Western-style high-fat diet increased inflammatory vaccine responses in mice.
But the researchers explicitly did not demonstrate that changing diet alters vaccine reactions in people.
The human dietary findings were observational.
People who eat different diets also differ in many other ways, and the study did not randomly assign participants to different diets.
The high-fat-diet experiment was conducted in mice, while the food-additive findings came from laboratory experiments.
It would therefore be inaccurate to claim that eating a plant-based diet will prevent fever after a vaccine.
There is also no evidence from this study that probiotics, supplements or commercial microbiome tests can reduce vaccine side effects.
Diabetes.co.uk has more information on what the gut microbiome is and how it interacts with metabolism and immunity.
Recent research has also linked patterns in the early-life microbiome with future type 1 diabetes risk, although that study similarly did not show that deliberately changing gut bacteria prevents diabetes.
What does this mean for people with diabetes?
The study involved healthy young adults receiving COVID-19 mRNA vaccines in 2021 and 2022.
It did not specifically investigate people with diabetes and should not be used to predict whether someone with type 1 or type 2 diabetes will develop vaccine side effects.
It also did not examine seasonal flu vaccination.
That distinction matters in the UK, where people with diabetes are among the clinical risk groups eligible for an annual NHS flu vaccination during the 2026/27 season.
The results provide no reason to avoid vaccination.
Nor does developing a fever necessarily mean the vaccine is working better or worse.
A fever reflects inflammatory activity, but this study was primarily examining why inflammatory reactions differ between people rather than proving a relationship between fever and vaccine effectiveness.
People with diabetes may notice temporary changes in glucose when they develop a fever or feel unwell after a vaccination, just as they can during other illnesses.
Monitoring glucose more closely and following normal sick-day guidance is therefore sensible where needed.
What happens next?
The researchers suggest the gut microbiome could eventually become a target for reducing unwanted inflammatory reactions.
But that remains a research question.
Clinical trials would first need to deliberately alter the microbiome in people and show that doing so changes vaccine reactions without compromising protection against infection.
Until those trials happen, the practical message is limited.
The study provides an intriguing explanation for why immune reactions differ between individuals, but it does not provide a diet, probiotic or microbiome treatment that people should use before being vaccinated.
Primary study: Science – The human gut microbiome primes fever after vaccination
