ScienceNot yet confirmed elsewhere1 publisher2 min readPublished
People who ran a fever after a COVID shot had more bacterial flagellin in their guts
Researchers who tracked more than 170 people around a COVID shot found that those who ran a fever had more gut inflammation, in a study in Science. The human link is correlational, and the team has only begun testing whether the bacteria behind the fever can be reduced.
The Scientist · Science desk
What happened
- Flagellin forms the tail-like flagella that bacteria use to swim, so the microbes tied to fever appeared more mobile in the gut than others.
- Samples were taken before and after each person's second or third COVID dose, and those who later ran a fever shared similar gut microbiome traits.
- Self-reported vegetarians tended to carry lower flagellin levels, a hint that diet plays some part in how much of the protein a gut holds.
- The senior author, Ruth Ley, directs the microbiome science department at the Max Planck Institute for Biology Tubingen in Germany.
Compiled by The ScientistSomething wrong?How this is made
Why it matters
- constraint The clean causal step sits in mice; in people the result is observational, so the study cannot yet show that cutting flagellin would cut a person's fever.
- capability Because the fever-linked microbes were the swimmers, their motility is a concrete target that future work could try to reduce.
- precedent The work points vaccine-tolerability research toward the gut, with the stated goal of raising uptake by softening side effects.
The human half of this is a correlation, and a correlation cannot say which way cause runs. The follow-up in mice is where the team tested direction. Ley's group gave genetically engineered mice the human bacteria tied to fever, and the animals mounted a response equivalent to a human fever, strongest in mice that could sense flagellin [9].
Mice bred without the flagellin receptor were less affected [10]. The receptor was the only thing that differed between the two groups, so the weaker response points to flagellin and not some other part of the bacteria. The reactions scaled together across species. "The worse the fever in the people, the more the temperature dropped in the mice," Ley said [12]. Mice do not run fevers; they drop into hypothermia as their version of the same immune response [13], and that drop tracked the human fever grade [11].
The study does not show whether any of this can be acted on in people. It is still unclear why some guts carry more flagellin than others [14].
"It would make sense that, if you could tamp down the motility of the bacteria, we would predict that you wouldn't react as strongly in terms of the fever," Ley said. "But that's all very much future research" [16].
Calling vaccine fever predictable runs a little ahead of the paper. It reports an association between a gut protein and a side effect.
What to watch
- Whether a stool test can actually predict who spikes a fever, tested prospectively rather than after the fact.
- Whether reducing bacterial motility or flagellin in people lowers fever, the future work Ley flags.
- Whether the diet signal, vegetarians with lower flagellin, holds up under controlled testing.
Clarity's read
What the record supports and how the coverage leans. The claims behind it follow.
Reality
- Evidence50
- Adoption
- Insufficient
- Hype gap+15
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- [2]
Researchers collected stool samples from more than 170 people in connection with a COVID vaccine dose.
- [3]
The stool samples were taken before and after participants' second or third dose of a COVID vaccine.
- [4]
People who experienced fever after the shot tended to share similar microbiome traits.
- [5]
People with worse fever tended to have more of a protein called flagellin in their systems than those with little to no fever.
- [6]
Flagellin makes up the tail-like flagella that bacteria use to move, suggesting the fever-associated microbes had greater motility, or ability to move around.
- [7]
Participants with high-fever symptoms also tended to have greater gut inflammation than their peers.
- [8]
Ruth Ley is the study's senior author and director of the department of microbiome science at the Max Planck Institute for Biology Tubingen in Germany.
- [9]
In a follow-up experiment, genetically engineered mice exposed to the fever-associated human bacteria showed a response equivalent to a fever in humans, particularly those that could sense flagellin.
- [10]
Mice without flagellin receptors were less affected, indicating a direct link between flagellin and an immune system response.
- [11]
The levels of fever in the humans correlated with the levels of the equivalent reaction in the mice.
- [12]
Ley said: "The worse the fever in the people, the more the temperature dropped in the mice."
- [13]
Mice typically experience hypothermia as part of their immune response, which serves a similar function to a fever in humans.
- [14]
It is still unclear why some people have higher levels of flagellin in their guts than others.
- [15]
Self-reported vegetarians tended to have lower flagellin levels, according to the study.
- [16]
Ley said: "It would make sense that, if you could tamp down the motility of the bacteria, we would predict that you wouldn't react as strongly in terms of the fever. But that's all very much future research."
- [17]
Ley hopes the results could eventually help fight this side effect of vaccines and, by extension, encourage higher vaccination rates.
Sources
1 independent publisher whose own reporting we read for this story.
- scientificamerican.comFeverish after a vaccine? The reason could be your gut microbiome
1 article · October 9, 2026
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Topics
- Gut Microbiome and Protein FermentationFollow
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