Potential cost and combinatorial effects of commensal gut microbes on survival of individual honey bees

The western honey bee, Apis mellifera , is attracting attention as an experimental model to investigate general interactions between hosts and gut microbiota because of their noteworthy simple and stable bacterial community. Here, we systematically explore the effect of five core bacteria, Snodgrassella alvi, Bifidobacterium asteroides , Bombilactobacillus Firm-4, Lactobacillus Firm-5, and Gilliamella apicola , on the longevity of individual honey bees. Generating gnotobiotic bees harboring all 32 different combinations of the core bacteria, we found that bacterial colonization generally reduces the host lifespan. This indicates that despite commensal gut microbes coevolved with the host, their presence is in principle costly for survival of individual bees. Regression analysis including higher-order interactions reveals that bacterial interactions have significant impacts on the host lifespan and show a qualitative trend: 2- and 4-way interactions exhibit positive, while 3- and 5-way interactions are negative. Numerical simulations based on a general Lotka-Volterra model demonstrate that the observed trend is reproduced when competitive interactions dominate in the bacterial community. This study combining empirical and theoretical approaches suggests the general costs of harboring gut microbiota and the stabilization of the bacterial community by higher-order interactions, which will advance our understanding of how commensal gut microbes and their interactions specifically influence host physiology. Importance Gut microbes are recognized for their profound effects on the host physiology. They provide numerous benefits to their hosts, whereas gut dysbiosis leads to various disease or mental impairment. Although understanding of such association with hosts is of pivotal importance, many animals have complex gut microbiome comprised of hundreds of bacterial species, most of which cannot be cultured in the laboratory. This is a big challenge to disentangle intimate interactions of commensal microbes with their hosts. Here, we exploit characteristics of honey bee gut microbiota, which consists of only five core bacteria, to generate gnotobiotic bees harboring defined bacterial communities with all 32 ( i.e ., 2 5 ) possible combinations. This large-scale analysis uncovers not only individual impacts of the core species but also combinatorial effects generated by their interaction on the host lifespan. Finally, using simple mathematical models, we explain that the combinatorial effects are largely derived from competitions between gut microbes.