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The evolution of multicellularity has not only enabled the specialization of eukaryote cell types, but also provided stable confined habitats for microbes to engage in symbiotic associations with metazoans. Animal–microbe interactions presented new challenges, such as self/nonself recognition, but also new opportunities that have shaped the evolution and diversification of holobionts. Sponges (Porifera), as one of the most basal animals, provide a fundamental resource to decipher key mechanisms of animal–microbe interactions with implications for our understanding of the interactions between more complex invertebrates/vertebrates and microbes. Significant progress has been made in our comprehension of the metabolic interactions and (meta-) genomic repertoires of sponge symbioses and the reader is kindly referred to several excellent