With emerging diseases on the rise, there is an urgent need to identify and understand novel mechanisms of prophylactic protection in vertebrate hosts. Inducing resistance against emerging pathogens through prophylaxis is an ideal management strategy that may impact pathogens and their host-associated microbiome. The host microbiome is recognized as a critical component of immunity, but the effects of prophylactic inoculation on the microbiome are unknown. In this study, we investigate the effects of prophylaxis on host microbiome composition, focusing on the selection of anti-pathogenic microbes contributing to host acquired immunity in a model host–fungal disease system, amphibian chytridiomycosis. We inoculated larval Pseudacris regilla against the fungal pathogen Batrachochytrium dendrobatidis ( Bd ) with a Bd metabolite-based prophylactic. Increased prophylactic concentration and exposure duration were associated with significant increases in proportions of putatively Bd -inhibitory host-associated bacterial taxa, indicating a protective prophylactic-induced shift towards microbiome members that are antagonistic to Bd. Our findings are in accordance with the adaptive microbiome hypothesis, where exposure to a pathogen alters the microbiome to better cope with subsequent pathogen encounters. Our study advances research on the temporal dynamics of microbiome memory and the role of prophylaxis-induced shifts in microbiomes contributing to prophylaxis effectiveness. This article is part of the theme issue ‘Amphibian immunity: stress, disease and ecoimmunology’.

Background Host microbiomes may differ under the same environmental conditions and these differences may influence susceptibility to infection. Amphibians are ideal for comparing microbiomes in the context of disease defense because hundreds of species face infection with the skin-invading microbe Batrachochytrium dendrobatidis (Bd), and species richness of host communities, including their skin bacteria (bacteriome), may be exceptionally high. We conducted a landscape-scale Bd survey of six co-occurring amphibian species in Brazil’s Atlantic Forest. To test the bacteriome as a driver of differential Bd prevalence, we compared bacteriome composition and co-occurrence network structure among the six focal host species. Results Intensive sampling yielded divergent Bd prevalence in two ecologically similar terrestrial-breeding species, a group with historically low Bd resistance. Specifically, we detected the highest Bd prevalence in Ischnocnema henselii but no Bd detections in Haddadus binotatus. Haddadus binotatus carried the highest bacteriome alpha and common core diversity, and a modular network partitioned by negative co-occurrences, characteristics associated with community stability and competitive interactions that could inhibit Bd colonization. Conclusions Our findings suggest that community structure of the bacteriome might drive Bd resistance in H. binotatus, which could guide microbiome manipulation as a conservation strategy to protect diverse radiations of direct-developing species from Bd-induced population collapses.