The conservation of coral reefs faces unprecedented threats due to climate change. The interactions between corals and their microbiome are considered fundamental to the resilience of the hosts in a rapidly warming ocean. However, the capacity to exploit these interactions for conservation purposes remains severely limited. This project addresses one of the most pressing challenges of modern Biology — the preservation of coral reefs and octocoral forests in a warming ocean — using microbiome manipulations applied to octocorals (Cnidaria, Anthozoa, Octocorallia), a fundamental but still underexplored animal clade, of critical importance for the functioning of marine benthic ecosystems. It is well established that corals live in symbiosis with complex microbial consortia, composed of microeukaryotes, prokaryotes, and viruses (19), which may act as mutualists in key processes related, for example, to the nutrition, detoxification, or chemical defense of the host (13). Similar to the hexacorals (Hexacorallia, formers of calcium carbonate skeletons), octocorals harbor diversified prokaryotic communities (20), generally distinct in their structure and taxonomic composition from those of the surrounding environment and frequently specific at the level of the host genus or species (1, 21). Intriguingly, although mass mortality events associated with rising temperatures and the proliferation of pathogens have been reported for octocorals in the Mediterranean Sea (22, 23), there is emerging evidence pointing to a transition from hexacoral-dominated reefs to octocoral-dominated reefs in shallow-water tropical reefs (24). This phenomenon raises interest regarding the physiological and ecological characteristics that may favor the survival or the decline of octocorals in the current context of climate change. However, the role of the microbiome associated with octocorals in this dynamic is still unknown. To overcome these limitations, our team will integrate expertise in advanced coral aquaculture, experimental biology, and microbiology (11, 14, 15) with innovative culturomics and metagenomics approaches to investigate the response of octocorals to the combined effects of increased water temperature and pathogenic stress, simultaneously evaluating the structure and the function of the microbiome in octocorals (1, 2, 6, 21, 25). We will resort to a mesocosm infrastructure to study octocorals under controlled conditions of water warming and pathogenic pressure, in order to determine whether supplementation with probiotics can prevent or remedy the deleterious effects of warming and of pathogen proliferation in these marine organisms. Recently, we discovered that the tropical octocoral Sclerophytum presents signs of physiological decline when exposed to simulations of heat waves. This decline is significantly exacerbated and results in high mortality rates in the presence of spores of the fungus Aspergillus sydowii. These results reveal a synergism between abiotic and biotic stress factors that accelerates the decline of octocorals in comparison with the isolated effects of each of these factors (Marques et al., data not yet published). Benefiting from a collection of putatively beneficial bacteria associated with octocorals (25, 26) and from a unique expertise in the application of probiotics to prevent stress symptoms in corals (14, 15), we will test in this project the efficacy of a probiotic cocktail designed to mitigate the mortality induced by A. sydowii in octocorals. We hypothesize that the topical administration of a mixture of chitinolytic bacteria associated with octocorals, antagonists of A. sydowii in vitro, will protect the octocoral Sclerophytum from infection by this pathogen under warming conditions. We anticipate that rapid and drastic alterations will occur in the structure of the octocoral microbiome (including prokaryotes, microeukaryotes, and bacteriophages) when subjected to warming and to pathogen load. This state of dysbiosis may be characterized by the reduction of typical octocoral symbionts (e.g., Symbiodiniaceae, Endozoicomonadaceae) and by the increase of opportunists (e.g., Vibrio, Flavobacteriaceae) in the holobiont under A. sydowii infection potentiated by warming. However, eubiosis should prevail under probiotic treatment, promoting the stabilization of the symbiosis and the homeostasis of the coral holobiont, through the enrichment in “Eukaryotic-like proteins” (ELPs) and CRISPR-Cas antiviral defense systems and endonucleases in the prokaryotic consortium of healthy octocorals (1, 2). This project will contribute significantly to the advancement of knowledge about the functionality of octocoral microbiomes and will introduce new methodologies based on microbiome engineering, relevant to efforts for the restoration of marine ecosystems.