Gut bacteria that break down a sugar known as fucose could be compromising our immune response to the COVID mRNA vaccine, a study has revealed.

The researchers from the Okinawa Institute of Science and Technology (OIST) in Japan report that increased "fucose" digestion by bacteria in the gut before vaccination was associated with lower numbers of T-cells activated by vaccination.

The findings, published in the journal Communications Biology, illustrate the important impact that the trillions of bacteria in our gut -- collectively called our 'gut microbiome' -- have on our immune health and add a missing piece to the puzzle of why vaccination varies in effectiveness from person to person.

"Not everyone who gets the same vaccine receives an equal level of protection, but we still don't really understand why people respond so differently," said Prof. Hiroki Ishikawa, who leads the OIST Immune Signal Unit.

In the study, Ishikawa and his colleagues took a stool sample and multiple blood samples from 96 healthy participants living in Okinawa, starting before the first dose of the vaccine, and ending a month after the second dose.

They looked at all the genes from immune cells in the blood and bacteria in the gut to see if there was any association with an individual's T-cell and antibody levels.

The researchers did find that individuals that had a lower T-cell response also had a gut microbiome with a high activity of fucose digestion.

The team also found that individuals with a reduced T-cell response had higher expression of two genes, FOS and ATF3, prior to vaccination.

Individuals with higher expression of FOS and ATF3 prior to vaccination also had microbiomes with high activity of fucose digestion, suggesting that the gut's impact on the immune system is through a pathway that involves FOS and ATF3.

"The mechanism is not yet proven, but we propose that fucose digestion leads to increased baseline expression of FOS and ATF3 in blood immune cells, which in turn weakens the response to the COVID-19 vaccine," said Masato Hirota, first study author.

While this research focused on the response to the COVID-19 Pfizer mRNA vaccine, the researchers believe their results could also be relevant for other mRNA vaccines in development that protect against other infectious diseases, and even cancer.