Gut Bacteria Protein Linked to Fever After COVID Vaccines in 171 Adults as Mouse Tests Point to Diet

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Different Workouts Suited Different MarkersA pooled analysis of 53 trials found that different exercise types helped different metabolic markers. Most of the evidence was low certainty. David Ryder | Getty Images Share on Twitter Share on Facebook Share on Pocket Why do some people spend the day after a vaccine on the couch with a fever while others feel nothing? A new study in the journal Science points to an unexpected factor: a protein made by certain gut bacteria.

Researchers led by the Max Planck Institute for Biology Tübingen in Germany found that adults who ran higher temperatures after mRNA COVID-19 vaccines had gut microbes that produced more flagellin, the protein bacteria use to build the whip-like tails that help them move. The study tracked 171 healthy young adults, most of whom were receiving a third mRNA dose.

The finding offers a possible biological explanation for a common, usually short-lived side effect. It does not show that changing diet can prevent fever.

Participants took their own oral temperatures three times a day for about two weeks around vaccination, according to an earlier preprint of the research. Researchers compared each person’s readings with their own normal temperature at the same time of day.

People with larger temperature rises had more active flagellin genes in their gut bacteria before they were vaccinated. Much of that came from a family of bacteria called Lachnospiraceae, according to a News-Medical summary of the study. These high responders also showed more low-grade inflammation in blood and stool samples at baseline.

Fever and flu-like symptoms are among the most common reactions to mRNA vaccines, yet not everyone gets them, and people who react often do so again with later doses. That consistency suggested an individual factor, and the gut microbiome, which helps shape immune activity throughout the body, was a logical place to look.

The immune system recognizes flagellin as a sign of bacteria, and it can switch on inflammatory pathways. The researchers propose that a steady supply of flagellin from the gut keeps the immune system slightly primed, so a vaccine triggers a stronger fever response in some people.

Ruth Ley, director of the institute’s Department of Microbiome Science, said in a Max Planck Society release that “microbial flagellin is one contributor to this baseline immune state.”

To test whether the microbes themselves played a role, the team transferred gut bacteria from participants into germ-free mice. Mice that received microbes from high responders had larger temperature changes and more inflammatory signaling after vaccination, an effect that depended partly on the animals’ ability to sense flagellin.

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

The researchers were careful about what this means for people. “While we could not show that diet determines vaccine responses in humans,” said lead author Kelsey Huus, who did the work at Max Planck, the findings suggest diet is one factor that can shape an inflammatory microbiome. She said studies in people will be needed to learn whether changing diet can alter flagellin production and vaccine fever.

In an accompanying Science Perspective, immunologist Bali Pulendran wrote that diet and microbial ecology are “not immutable,” raising the possibility that people could one day prepare for vaccination deliberately, News-Medical reported.

Flagellin levels, gut inflammation and diet did not appear to affect antibody responses to the vaccines, the researchers reported. In other words, the gut factors linked to fever were not linked to weaker or stronger antibody production.

That matters because fear of side effects can discourage people from returning for later doses, the researchers noted. The work may eventually help clinicians explain why some people consistently react more strongly than others.

The evidence has clear limits. The human findings are associations, not proof of cause, and diet was self-reported. Participants were healthy young adults, so the results may not apply to older people, children, or those with chronic illness. The food-additive findings come only from lab dishes and mice, and the study focused on mRNA COVID-19 vaccines, so it is not known whether the same pattern holds for flu or other shots.

For most people, side effects such as a low-grade fever go away within a few days and reflect the immune system responding to the vaccine. Rest, fluids, and over-the-counter fever reducers, if a clinician says they are appropriate, are common ways to manage discomfort.

People should not change their diet, take probiotics, or skip a recommended vaccine based on this study. No human trial has tested whether altering gut bacteria before a shot reduces side effects.

People should seek medical care for a high fever lasting more than a couple of days, trouble breathing, swelling of the face or throat, chest pain or a racing heartbeat after vaccination. Those symptoms are uncommon but need prompt evaluation. Anyone with a history of strong reactions can talk with a clinician about timing a shot before a day when rest is possible. MedicalDaily will report on human diet studies when results become available.

Adults who developed higher temperatures after mRNA COVID-19 vaccines had gut bacteria that produced more flagellin, a protein that can trigger inflammation.

Flagellin is the protein bacteria use to build flagella, the tail-like structures that help them move. The immune system recognizes it as a sign of bacteria.

That was not shown in people. Food additives and a Western-style diet increased flagellin or inflammation in lab and mouse experiments, but human diet trials have not been done.

Did gut bacteria affect vaccine protection?

The researchers found flagellin, gut inflammation, and diet did not appear to affect antibody responses to the vaccines.

The study followed 171 healthy young adults, most receiving a third mRNA COVID-19 dose, plus experiments in mice.

Should I take probiotics before a vaccine?

There is no evidence that probiotics or diet changes reduce vaccine fever. Talk with a clinician before making changes.

Seek care for a high fever lasting more than a couple of days, trouble breathing, facial swelling, chest pain, or a racing heartbeat.