Your Gut Bacteria Could Decide if a Vaccine Gives You Fever

Some people spend the day after a COVID shot on the couch with a fever. Others feel nothing at all. Scientists have spent years wondering why the same vaccine produces such different reactions in different arms. A study published this month in the journal Science points to an unexpected suspect: the gut bacteria living in your digestive tract.

Researchers led by Ruth Ley of the Max Planck Institute for Biology Tübingen found that adults whose gut bacteria produced more of a protein called flagellin were more likely to run a fever after an mRNA COVID-19 vaccine. The work tracked 171 healthy young adults, most of them receiving a third dose, and was reported by Medical Daily as a possible biological explanation for a common, usually short-lived side effect.

What the researchers found

The team built its case on the µHEAT study, short for Microbial-Human Ecology and Temperature. Participants provided stool samples for microbiome sequencing, gave blood so the team could measure immune markers, and took their own oral temperatures three times a day for roughly two weeks around vaccination, comparing each reading with their usual temperature at the same time of day.

The pattern was clear. Participants whose temperature rose by at least 0.8 degrees Celsius after vaccination already showed distinct biology before the shot: more active flagellin genes in their gut bacteria and more low-grade inflammation in blood and stool samples. Flagellin is the protein bacteria use to build the whip-like tails that help them move, and much of it came from a bacterial family called Lachnospiraceae, including a genus known as Waltera, according to a summary of the study reported by News-Medical.

The reason flagellin matters is that the immune system treats it as a danger signal. Dedicated receptors, including a sensor known as Toll-like receptor 5, recognize the protein and switch on inflammatory pathways. The researchers propose that a steady supply of flagellin from gut bacteria keeps the immune system slightly primed, so a vaccine pushes some people's systems past the threshold that registers as fever. Ley said in a Max Planck Society release that "microbial flagellin is one contributor to this baseline immune state."

The mouse experiments backed it up

To check whether the microbes themselves were responsible, the team transferred gut bacteria from participants into germ-free mice. Mice that received microbes from the people with the largest temperature rises developed larger temperature changes and stronger inflammatory signaling after vaccination, including higher levels of interleukin-6, a molecule that helps drive inflammation. When the mice lacked key flagellin-sensing receptors, TLR5 and NLRP4, the effect weakened, though it did not disappear, a sign that flagellin is a single driver among several.

The results fit a long-standing observation about vaccines: people who react to an initial dose tend to react to the next. That consistency suggested something stable about the individual rather than chance, and the community of gut bacteria, which shapes immune activity throughout the body, was a natural place to look.

Diet is a suspect, not a prescription

Food entered the picture in the laboratory. Certain food additives increased flagellin production by gut bacteria grown in dishes, and a high-fat, Western-style diet worsened inflammatory reactions after vaccination in mice. Co-author Benoit Chassaing of Inserm and the Institut Pasteur said the findings suggest components of an industrialized diet may promote the growth of flagellated gut bacteria.

The researchers were careful about what that means for people. Lead author Kelsey Huus noted that the team could not show diet determines vaccine responses in humans, and participants reported their own diets rather than following controlled ones. Human trials would be needed to learn whether changing what a person eats can alter how much flagellin gut bacteria produce and whether a shot brings on fever. In an accompanying Science Perspective, immunologist Bali Pulendran wrote that diet and microbial ecology can change, raising the possibility that people might someday prepare for vaccination deliberately, according to News-Medical.

There is also good news in the fine print: flagellin levels, gut inflammation, and diet did not appear to affect antibody responses to the vaccines. The factors tied to fever were not tied to weaker protection.

What this means for your next shot

For now, the practical takeaway is narrow. There is no evidence that probiotics, diet changes, or any gut-health product will soften vaccine side effects, and the study looked only at mRNA COVID-19 vaccines in healthy young adults, so it is unknown whether the pattern holds for flu shots or for older people and children. Fever and flu-like symptoms remain among the most common vaccine reactions, usually fade within a few days, and reflect the immune system doing its job. The researchers noted that fear of side effects can keep people from returning for later doses, and understanding why reactions differ may eventually help clinicians explain them. Anyone with a high fever lasting more than a couple of days, trouble breathing, facial swelling, or chest pain after vaccination should seek medical care promptly.