RT Journal Article SR Electronic T1 Chemical Impacts of the Microbiome Across Scales Reveal Novel Conjugated Bile Acids JF bioRxiv FD Cold Spring Harbor Laboratory SP 654756 DO 10.1101/654756 A1 Robert A. Quinn A1 Alison Vrbanac A1 Alexey V. Melnik A1 Kathryn A. Patras A1 Mitchell Christy A1 Andrew T. Nelson A1 Alexander Aksenov A1 Anupriya Tripathi A1 Greg Humphrey A1 Ricardo da Silva A1 Robert Bussell A1 Taren Thron A1 Mingxun Wang A1 Fernando Vargas A1 Julia M. Gauglitz A1 Michael J. Meehan A1 Orit Poulsen A1 Brigid S. Boland A1 John T. Chang A1 William J. Sandborn A1 Meerana Lim A1 Neha Garg A1 Julie Lumeng A1 Barbara I. Kazmierczak A1 Ruchi Jain A1 Marie Egan A1 Kyung E. Rhee A1 Gabriel G. Haddad A1 Dionicio Siegel A1 Sarkis Mazmanian A1 Victor Nizet A1 Rob Knight A1 Pieter C. Dorrestein YR 2019 UL http://biorxiv.org/content/early/2019/06/03/654756.abstract AB 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 consortia1. The microbial residents within these organ systems are increasingly well characterized, yielding a good understanding of human microbiome composition, but we have yet to elucidate the full chemical impact the microbiome exerts on an animal and the breadth of the chemical diversity it contributes2. A number of molecular families are known to be shaped by the microbiome including short-chain fatty acids, indoles, aromatic amino acid metabolites, complex polysaccharides, and host lipids; such as sphingolipids and bile acids3–11. 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 units12, a plethora of molecular diversity remains to be discovered. Here, we use unique mass spectrometry informatics approaches and data mapping onto a murine 3D-model13–15 to provide an untargeted assessment of the chemical diversity between germ-free (GF) and colonized mice (specific-pathogen free, SPF), and report the finding of novel bile acids produced by the microbiome in both mice and humans that have evaded characterization despite 170 years of research on bile acid chemistry16.