Mucosal vaccines, which aim to induce strong immunity at mucous membranes such as the mouth, respiratory tract and intestines where infections begin, are drawing attention as next-generation vaccines. But mucosae are insensitive to external substances, making it difficult to elicit sufficient immunity even when a vaccine is administered. A domestic research team has offered a clue to solving this challenge by using gut microbial metabolites.
The team led by Professor Lim Shin-hyeok of the Pohang University of Science and Technology POSTECH Department of Life Sciences and Graduate School of Convergence announced on the 27th that it has, for the first time in the world, identified that the metabolite "butyrate" produced by gut microbes activates key cells of mucosal immunity to promote antibody production and even enhance mucosal vaccine responses. The findings were published on the 21st (local time) in the international journal Microbiome.
The target the team focused on was T follicular helper T cells (Tfh), which play an important role in intestinal mucosal immunity. Tfh cells help B cells produce antibodies and are known as key regulators that determine the direction and strength of immune responses. The team judged that for mucosal vaccines to work properly at mucosal sites, it is crucial to understand how Tfh cells originating from mucosal tissues operate.
In experiments, Tfh cells originating from Peyer's patch, an immune organ in the small intestine, induced production of the mucosal antibody IgA much more strongly than spleen-derived Tfh cells responsible for systemic immunity. Notably, in a mouse model in which specific gut microbes were removed, both Tfh cells and IgA antibodies decreased; when the microbes were supplied again, the immune response recovered, confirming the link between gut microbes and mucosal immunity.
At the center was the metabolite "butyrate," a short-chain fatty acid produced by beneficial bacteria. The team analyzed that butyrate acts as a signal to activate Tfh and B cells, boosting the IgA antibody response. In fact, in a model administered tributyrin, a butyrate precursor, IgA production increased and defense against Salmonella infection also improved.
Lim said, "We have shown that gut microbes go beyond aiding digestion to directly regulating the functions of key immune cells and vaccine responses," adding, "This could lead to the development of next-generation mucosal vaccines and immunotherapy technologies that harness microbial metabolites."
References
Microbiome (2026), DOI: https://doi.org/10.1186/s40168-025-02284-7