The commensal microbiota is a rich community of hundreds of bacterial species colonising the mammalian host, most of which reside in the gastrointestinal tract and interface closely with the local immune cell rich mucosa. Co-evolution of microbes and their host over millions of years has driven the development of extensive reciprocal host microbe interactions. There is accumulating evidence that gut‑resident microbes have a profound influence on host immune responsiveness to infection and vaccination, not only locally, but also at distal sites. How microbes exert these systemic immunomodulatory effects and the subsequent impact on protective immunity has yet to be extensively defined.

Using the subcutaneous trivalent influenza vaccination (TIV) in mice as a model to study the systemic reach of gut-resident microbes and associated metabolites, we have observed that short-term administration of broad spectrum antibiotics drastically reduces antigen‑specific antibody production. We then examined the impact of antibiotic treatment on the frequency, activation status and migration of multiple immune cell subsets in the skin‑draining lymph node of mice following TIV to determine how deprivation of microbial‑associated signals leads to the observed impaired antibody response. In particular, we assessed the frequency and phenotype of germinal centre B cells, T follicular helper cells and a number of antigen‑presenting cell subsets.

This work illustrates how commensal microbiota composition of the host may govern vaccine efficacy. Defining the mechanisms by which commensal microbes in the gut influence distal immune cells could provide a functional roadmap of gut-resident microbial communities and inform nutritional and therapeutic approaches to improve the efficacy of existing vaccines.