The findings shed light on the important role of the gut microbiome in our overall immune health and offer insights into why some individuals may not respond as effectively to the COVID-19 vaccine.

Not all individuals who receive the same vaccine are equally protected, and the reasons for this variation are still unclear. By investigating the underlying causes, it may be possible to predict an individual’s vaccine response and devise novel techniques to enhance the immune response.

According to a recent study by researchers at the Okinawa Institute of Science and Technology (OIST), gut bacteria that digest a specific sugar called fucose may be responsible for weakening our immune response to the COVID-19 mRNA vaccine.

The study suggests that higher levels of fucose digestion by gut bacteria before receiving the vaccine could lead to lower numbers of activated T-cells.

These blood immune cells are crucial in fighting infections by multiplying in response to a specific virus or bacteria.

The findings highlight the potential impact of gut bacteria on our immune system’s ability to respond to the COVID-19 vaccine.

In a report published today in Communications Biology, the researchers reveal the critical influence that the vast number of bacteria present in our gut, collectively referred to as our ‘gut microbiome’, has on our immune system. This research adds a crucial component to the puzzle of why the effectiveness of vaccination can vary from one individual to another.

“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,” remarks Professor Hiroki Ishikawa, who leads the OIST Immune Signal Unit. “If we can get to the bottom of what causes this variation, we could predict how an individual might respond to a vaccine, and perhaps find new strategies to promote the immune response.”

Although the COVID-19 Pfizer mRNA vaccine was the focus of this study, the researchers think their findings may also apply to other mRNA vaccines that are currently being developed to fight against other infectious illnesses and even cancer.

Professor Ishikawa and his team conducted a study in Okinawa, collecting stool and blood samples from 96 healthy participants. The study spanned from before the first dose of the vaccine to a month after the second dose. The team carried out a comprehensive analysis, examining all immune cell genes in the blood and gut bacteria to determine if there was a correlation between T-cell and antibody levels in individuals.

In their study, the researchers discovered no notable association between antibody levels and the factors under investigation. However, they did observe that individuals with a lower T-cell response had a gut microbiome that exhibited a high degree of fucose digestion activity.

The group discovered that two genes, FOS and ATF3, showed greater expression in those who had a weaker T-cell response before immunization.

The genes are responsible for coding proteins that belong to the AP-1 transcription factors, which are crucial for the survival and activity of T-cells. Although the precise function of these proteins is yet to be determined, previous studies have shown their control over T-cell function.

Interestingly, those with higher expression of FOS and ATF3 before vaccination had microbiomes with elevated activity of fucose digestion, indicating a connection between gut health and immune system function via the FOS and ATF3 pathway.

“The mechanism is not yet proven,” adds First author Masato Hirota, “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.

“It’s clear that the gut bacteria have an important impact on the overall health of the immune system.”

To further understand the relationship between the microbiome, blood immune cells, and the overall immunological response, the team now intends to experimentally change the gut bacteria in mice and explore the precise mechanism of FOS and ATF3.

Source: 10.1038/s42003-023-04755-9

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