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ABSTRACT Marine sponge holobionts are prolific sources of natural products. One of the most geographically widespread classes of sponge-derived natural products is the bromotyrosine alkaloids. A distinguishing feature of bromotyrosine alkaloids is that they are present in phylogenetically disparate sponges. In this study, using sponge specimens collected from Guam, the Solomon Islands, the Florida Keys, and Puerto Rico, we queried whether the presence of bromotyrosine alkaloids potentiates metabolomic and microbiome conservation among geographically distant and phylogenetically different marine sponges. A multi-omic characterization of sponge holobionts revealed vastly different metabolomic and microbiome architectures among different bromotyrosine alkaloid-harboring sponges. However, we find statistically significant correlations between the microbiomes and metabolomes, signifying that the microbiome plays an important role in shaping the overall metabolome, even in low-microbial-abundance sponges. Molecules mined from the polar metabolomes of these sponges revealed conservation of biosynthetic logic between bromotyrosine alkaloids and brominated pyrrole-imidazole alkaloids, another class of marine sponge-derived natural products. In light of prior findings postulating the sponge host itself to be the biosynthetic source of bromotyrosine alkaloids, our data now set the stage for investigating the causal relationships that dictate the microbiome-metabolome interconnectedness for marine sponges in which the microbiome may not contribute to natural product biogenesis. IMPORTANCE Our work demonstrates that phylogenetically and geographically distant sponges with very different microbiomes can harbor natural product chemical classes that are united in their core chemical structures and biosynthetic logic. Furthermore, we show that independent of geographical dispersion, natural product chemistry, and microbial abundance, overall sponge metabolomes tightly correlate with their microbiomes. 

Abstract Regular exercise promotes whole-body health and prevents disease, but the underlying molecular mechanisms are incompletely understood^1–3. Here, the Molecular Transducers of Physical Activity Consortium⁴profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome and immunome in whole blood, plasma and 18 solid tissues in male and femaleRattus norvegicusover eight weeks of endurance exercise training. The resulting data compendium encompasses 9,466 assays across 19 tissues, 25 molecular platforms and 4 training time points. Thousands of shared and tissue-specific molecular alterations were identified, with sex differences found in multiple tissues. Temporal multi-omic and multi-tissue analyses revealed expansive biological insights into the adaptive responses to endurance training, including widespread regulation of immune, metabolic, stress response and mitochondrial pathways. Many changes were relevant to human health, including non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular health and tissue injury and recovery. The data and analyses presented in this study will serve as valuable resources for understanding and exploring the multi-tissue molecular effects of endurance training and are provided in a public repository (https://motrpac-data.org/).