Diet in the driving seat: natural diet-immunity-microbiome interactions in wild fish

Abstract

Natural interactions between the diet, microbiome and immunity are largely unstudied. Here we employ wild three-spined
sticklebacks as a model, combining field observations with complementary experimental manipulations of diet designed to mimic
seasonal variation in the wild. We clearly demonstrate that season-specific diets are a powerful causal driver of major systemic
immunophenotypic variation. This effect occurred largely independently of the bulk composition of the bacterial microbiome (which
was also driven by season and diet) and of host condition, demonstrating neither of these, per se, constrain immune allocation in
healthy individuals. Nonetheless, through observations in multiple anatomical compartments, differentially exposed to the direct
effects of food and immunity, we found evidence of immune-driven control of bacterial community composition in mucus layers.
This points to the interactive nature of the host-microbiome relationship, and is the first time, to our knowledge, that this causal
chain (diet → immunity → microbiome) has been demonstrated in wild vertebrates. Microbiome effects on immunity were not
excluded and, importantly, we identified outgrowth of potentially pathogenic bacteria (especially mycolic-acid producing
corynebacteria) as a consequence of the more animal-protein-rich summertime diet. This may provide part of the ultimate
explanation (and possibly a proximal cue) for the dramatic immune re-adjustments that we saw in response to diet change.