Our guts are home to a complex, dense and dynamic consortia of microbes, which can have a profound impact on our health. In this presentation, we will discuss how the mucosal immune system has evolved to minimize the risk from opportunistic bacterial pathogens such as Salmonella and E.coli. This requires us to explore secretory antibody function, intestinal physiology, bacterial glycobiology, within-host evolution and microbial ecology of the gut. A functional understanding of these systems reveals the potential for oral vaccine-based interventions that allow elimination of pathogen carriage (3, 4), with potential to expand into rational microbiota engineering.

1. High-avidity IgA protects the intestine by enchaining growing bacteria. Moor K, et al. 2017. Nature 544:498–502 doi:10.1038/nature22058
2. Inflammation boosts bacteriophage transfer between Salmonella. Diard M, et al. 2017. Science 355:1211-1215, doi:10.1126/science.aaf8451
3. A rationally designed oral vaccine induces immunoglobulin A in the murine gut that directs the evolution of attenuated Salmonella variants.Diard M, et al. Nat Microbiol. 2021 May 27. doi:10.1038/s41564-021-00911-1.
4. Vaccine-enhanced competition permits rational bacterial strain replacement in the gut. Lentsch V. et al. Accepted in Science 2025. bioRxiv doi.org/10.1101/2022.07.20.498444