Chemical Impacts of the Microbiome Across Scales Reveal Novel Conjugated Bile Acids

Robert A. Quinn(University of California San Diego), Alison Vrbanac(University of California San Diego), Alexey V. Melnik(University of California San Diego), Kathryn A. Patras(University of California San Diego), Mitchell P. Christy(University of California San Diego), Andrew T. Nelson(University of California San Diego), Alexander A. Aksenov(University of California San Diego), Anupriya Tripathi(University of California San Diego), Greg Humphrey(University of California San Diego), Ricardo Silva(University of California San Diego), Robert H. Bussell(University of California San Diego), Taren Thron(California Institute of Technology), Mingxun Wang(University of California San Diego), Fernando Vargas(University of California San Diego), Julia M. Gauglitz(University of California San Diego), Michael J. Meehan(University of California San Diego), Orit Poulsen(University of California San Diego), Brigid S. Boland(University of California San Diego), John T. Chang(University of California San Diego), William J. Sandborn(University of California San Diego), Meerana Lim(University of California San Diego), Neha Garg(Georgia Institute of Technology), Julie C. Lumeng(University of Michigan), Barbara I. Kazmierczak(Yale University), Ruchi Jain(Yale University), Marie E. Egan(Yale University), Kyung E. Rhee(University of California San Diego), Gabriel G. Haddad(University of California San Diego), Dionicio Siegel(University of California San Diego), Sarkis K. Mazmanian(California Institute of Technology), Victor Nizet(University of California San Diego), Rob Knight(University of California San Diego), Pieter C. Dorrestein(University of California San Diego)
bioRxiv (Cold Spring Harbor Laboratory)
June 3, 2019
10.1101/654756
Cited by 6Open Access
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Abstract

Abstract 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 1 . 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 contributes 2 . 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 acids 3–11 . 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 units 12 , a plethora of molecular diversity remains to be discovered. Here, we use unique mass spectrometry informatics approaches and data mapping onto a murine 3D-model 13–15 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 chemistry 16 .

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