PROJECT SUMMARY
Gut microbiota play critical roles in determining health, and the structure and function of these microbiota are
dependent on contemporary and historical host-microbe interactions. This application proposes research to
understand processes relating to the normal homeostasis between hosts and gut microbes. Gut microbiota
establishment and development is dependent on many factors, including innate and adaptive immunity, inter-
microbe interactions, and diet. Microbiota composition and stability are crucial to health, and disruption has
serve disease and pathogen infection consequences. A balance must be struck between rapid innate immune
responses to limit pathogen invasion, while moderating responses against beneficial coevolved mutualists.
Questions remain about how host immunity can, (1) maintain long-term associations with host-adapted core
microbes, but (2) contribute to microbiota perturbation during development, leading to dysbiosis and health-
related functional changes. The bumblebee gut microbiota model in this proposal provides an excellent
opportunity to gain a broad understanding of microbiota structure and function determined by host-microbe
interactions via innate immunity. The system is: (i) relatively simple, (ii) well described, (iii) unlike other insect
models, e.g. Drosophila, reflective of some key human-gut microbiota interactions, and (iv) accessible to
experimental manipulation, with available genomic and transcriptomic tools for hosts and microbes. The
overarching proposal goal is to test a hypothesis of immune-mediation of the gut microbiota, and elucidate how
host innate immunity can both disrupt microbiota structure, with functional consequences, and, together with
reciprocal coevolved interactions with microbes, determine long-term dynamics of specific host-microbe
associations. The first aim studies how host immune status (determined by experimental inoculation mimicking
pathogenic infection) affects gut microbiota structure and beneficial functioning, to be determined by MiSeq
sequencing and an infection protocol to assay the gut microbiota's protective function. This aim also assesses
the persistence of immune-mediated perturbation and the ability of social interactions to resurrect dysbiotic
microbiomes. The second main aim focuses on long-term specific associations between hosts and core
microbes, and the role of innate immunity in facilitating these interactions. Two non-exclusive hypotheses will
be tested: (a) host immune recognition and responses allow the persistence of beneficial core microbes, and
(b) long-term associations are facilitated by microbe resistance to host immune effectors. Comparisons will be
made between core native host bacteria and those from divergent host lineages in the induction of immune
responses on experimental establishment and the ability to resist host immune components. Research on
host-microbiota interactions is highly integrative, conceptually and technically. Thus, the proposed research
fulfills a primary AREA program goal by exposing undergraduate students to technique-rich research based on
a hypothesis driven framework, which will enhance understanding of a topic of clear biomedical importance.
