Multi-omics Analysis Reveals Important Role for Microbial-derived Metabolites from <i>Botryllus schlosseri</i> in Metal Interactions

Abstract Marine microbial communities govern many of the biological and chemical processes in the ocean, including element cycles, ecosystem health, and disease. Marine organisms are surrounded by microbes and complex molecular interactions occur between bacterial symbionts, eukaryotic hosts, and their pathogens or prey. Trace metals in the ocean can be either beneficial or detrimental to marine life depending on their concentrations and bioavailability. Multiple marine tunicate species are known to bioaccumulate trace metals in their mantel, and research suggests tunicate microbiota plays an important role in this process. Botryllus schlosseri , a marine colonial tunicate, has become a model organism for cellular and developmental studies, yet its ecological interactions are still not well understood. Using an integrated multidisciplinary approach, we established a comprehensive baseline and explored correlations between members of the B. schlosseri microbiome, metabolome, and metallome to elucidate the ecological effects of trace metals in host-microbe-pathogen interactions. We identified significant correlations between metals, including manganese, nickel, cerium, zinc, and cobalt, with various metabolites and bacterial taxa. These findings offer insights into B. schlosseri biological and chemical interactions with their symbionts and their environment, contributing to bridging the knowledge gap of host-microbiome-environment interactions and establishing a foundation for continuing research on the ecological effects of trace metals in these biological systems. Graphical Abstract Highlights Botryllus schlosseri tissue was highly enriched in metals compared to seawater B. schlosseri microbiome ß-diversity significantly different from seawater Pan-metabolome indicated microbial metabolites in core and flexible metabolome Multi-omics revealed interactions between metals, metabolites, and microbes