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Bae, Sena

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Bae, Sena

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    Global Chemical Impact of the Microbiome Includes Novel Bile Acid Conjugations
    (Springer Nature, 2020-02-26) Quinn, Robert; Melnik, Alexey; Vrbanac, Alison; Patras, Kathryn; Christy, Mitchell; Zsolt, Bodai; Belda-Ferre, Pedro; Tripathi, Anupriya; Chung, Lawton; Quinn, Melissa; Humphrey, Greg; Panitchpakdi, Morgan; Weldon, Kelly; Aksenov, Alexander; da Silva, Ricardo; Avila-Pacheco, Julian; Clish, Clary; Bae, Sena; Mallick, Himel; Franzosa, Eric; Lloyd-Price, Jason; Bussell, Robert; Thron, Taren; Nelson, Andrew; Wang, Mingxun; Leszczynski, Eric; Vargas, Fernando; Gauglitz, Julia; Meehan, Michael; Gentry, Emily; Arthur, Timothy; Downes, Michael; Fu, Ting; Welch, Ryan; Komor, Alexis; Poulsen, Orit; Boland, Brigid; Chang, John; Sandborn, William; Lim, Meerana; Garg, Neha; Lumeng, Julie; Xavier, Ramnik; Kazmierczak, Barbara; Jain, Ruchi; Egan, Marie; Rhee, Kyung; Ferguson, David; Evans, Ronald; Raffatellu, Manuela; Vlamakis, Hera; Haddad, Gabriel; Siegel, Dionicio; Huttenhower, Curtis; Mazmanian, Sarkis; Nizet, Victor; Knight, Rob; Dorrestein, Pieter
    A mosaic of cross-phyla chemical interactions occurs between all metazoans and their microbiomes. In humans, the gut harbors the heaviest microbial load, but many organs, particularly those with a mucosal surface, associate with highly adapted and evolved microbial consortia. The microbial residents within these organ systems are increasingly well characterized, yielding a good understanding of human microbiome composition. However, we have yet to elucidate the full chemical impact the microbiome exerts on an animal and the breadth of the chemical diversity it contributes. A number of molecular families are known to be shaped by the microbiome including short-chain fatty acids, indoles, complex polysaccharides, host sphingolipids and bile acids. These metabolites profoundly affect host physiology and are being explored for their roles in both health and disease. Considering the diversity of the human microbiome, numbering over 40,000 operational taxonomic units, a plethora of molecular diversity remains to be discovered. In this study we used novel mass spectrometry informatics and visualization approaches to provide an untargeted assessment of the chemical contributions of the microbiome to an entire mammal by comparing germ-free (GF) and specific-pathogen free (SPF) animals. We found that the microbiome affected the chemistry of all murine organs. These affects were highlighted by novel amino acid conjugations of host bile acids that have evaded characterization despite the extensive research on bile acid chemistry. These new bile acid conjugates were enriched in dysbiotic disease states and directly agonized the farnesoid X receptor (FXR) resulting in changes in host bile acid metabolism.