HOST AND MICROBE FACTORS INFLUENCING COMPOSITION AND FUNCTIONING OF AN ACCESSIBLE GUT MICROBIOTA MODEL

PROJECT SUMMARYGut microbiota play critical roles in determining health, and the structure and function of these microbiota aredependent on contemporary and historical host-microbe interactions. This application proposes research tounderstand processes relating to the normal homeostasis between hosts and gut microbes. Gut microbiotaestablishment 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 hasserve disease and pathogen infection consequences. A balance must be struck between rapid innate immuneresponses 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 coremicrobes, 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 excellentopportunity to gain a broad understanding of microbiota structure and function determined by host-microbeinteractions via innate immunity. The system is: (i) relatively simple, (ii) well described, (iii) unlike other insectmodels, e.g. Drosophila, reflective of some key human-gut microbiota interactions, and (iv) accessible toexperimental manipulation, with available genomic and transcriptomic tools for hosts and microbes. Theoverarching proposal goal is to test a hypothesis of immune-mediation of the gut microbiota, and elucidate howhost innate immunity can both disrupt microbiota structure, with functional consequences, and, together withreciprocal coevolved interactions with microbes, determine long-term dynamics of specific host-microbeassociations. The first aim studies how host immune status (determined by experimental inoculation mimickingpathogenic infection) affects gut microbiota structure and beneficial functioning, to be determined by MiSeqsequencing and an infection protocol to assay the gut microbiota's protective function. This aim also assessesthe persistence of immune-mediated perturbation and the ability of social interactions to resurrect dysbioticmicrobiomes. The second main aim focuses on long-term specific associations between hosts and coremicrobes, and the role of innate immunity in facilitating these interactions. Two non-exclusive hypotheses willbe 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 bemade between core native host bacteria and those from divergent host lineages in the induction of immuneresponses on experimental establishment and the ability to resist host immune components. Research onhost-microbiota interactions is highly integrative, conceptually and technically. Thus, the proposed researchfulfills a primary AREA program goal by exposing undergraduate students to technique-rich research based ona hypothesis driven framework, which will enhance understanding of a topic of clear biomedical importance.