Why the same vaccine leaves some people feverish: clues in the gut

Two people get the same COVID-19 shot. One feels fine; the other spends the night with a fever. Fever is a common side effect, and it can make people wary of the next dose. A study in Science suggests part of the difference may lie in the bacteria living in our guts.

The researchers started with people. They collected stool from more than 170 people before and after a second or third dose, then compared those who ran worse fevers with those who had little or none. The high-fever group had more flagellin in their gut. Flagellin is the protein in the whip-like tails bacteria use to swim, so more of it suggests more mobile bacteria. That group also tended to show more gut inflammation.

A difference in stool samples could have many explanations, so the team moved to the lab. They exposed organoids, tiny lab-grown pieces of human intestine, to microbes from high-fever donors. Those microbiomes triggered stronger inflammation, and the response depended on flagellin.

Then came mice. Mice given fever-associated bacteria had a stronger temperature response, but only if they could sense flagellin. That points to flagellin doing something rather than just tagging along. There's a wrinkle: mice respond with a drop in temperature instead of a fever, so the mouse step parallels the human reaction rather than reproducing it.

The chain still has gaps. The human evidence is an association in about 170 people. Nobody yet knows why flagellin levels differ from person to person. Self-reported vegetarians tended to have lower levels, but diet wasn't tested as a way to change them. What the work offers is a testable explanation for a familiar puzzle: the same shot, landing in different guts.