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

Quinn, Robert A. and Thron, Taren and Mazmanian, Sarkis (2019) Chemical Impacts of the Microbiome Across Scales Reveal Novel Conjugated Bile Acids. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20191101-124547555

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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. 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. 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. 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. Here, we use unique mass spectrometry informatics approaches and data mapping onto a murine 3D-model 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.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/654756DOIDiscussion Paper
ORCID:
AuthorORCID
Mazmanian, Sarkis0000-0003-2713-1513
Alternate Title:Global Chemical Impacts of the Microbiome Include Unique Bile Acid Conjugates that Stimulate FXR
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. bioRxiv preprint first posted online Jun. 3, 2019. The authors would like to acknowledge funding from the National Institutes of Health under project 5U01AI124316-03, 1R03CA211211-01, 1R01HL116235 and R01HD084163. Additionally, B.S.B. was supported by UCSD KL2 (1KL2TR001444), J.L. by grant 13EIA14660045 from the American Heart Association. We would like to acknowledge Gail Ackerman for her contributions to curate the metadata. We further thank Alan Hofmann and Lee Hagey for their insightful discussions on structural characterization of bile acids. Data Availability: All metabolomics data is available at GNPS (g 232 nps.ucsd.edu) under the MassIVE id numbers: MSV000079949 (GF and SPF mouse data). Additional sample data: MSV000082480, MSV000082467, MSV000079134, MSV000082406. The sequencing data for the GF and SPF mouse study is available on the Qiita microbiome data analysis platform at Qiita.ucsd.edu under study ID 10801 and through the European Bioinformatics Institute accession number ERP109688. Author Contributions: PCD, RK and RQ designed the project. RQ, AA, AM, FV, JG, NG, AT, MC, ATN, MM, GH, RdS, and RB generated data. RQ, AV, AT and MC analyzed data. RQ, BB, ML, OP, JC, ML, JL, KP, BK, RJ, ME, KR, GH, KR, GC, WS and RB collected samples. PCD, RK, SM, VN and DS guided experimental 34 design and analysis. MW converted the data in GNPS, developed spectral search and molecular explorer. TT, VN and SM raised animals and guided experimental design. RQ and PD wrote the manuscript.
Funders:
Funding AgencyGrant Number
NIH5U01AI124316-03
NIH1R03CA211211-01
NIH1R01HL116235
NIHR01HD084163
University of California, San Diego1KL2TR001444
American Heart Association13EIA14660045
Record Number:CaltechAUTHORS:20191101-124547555
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20191101-124547555
Official Citation:Chemical Impacts of the Microbiome Across Scales Reveal Novel Conjugated Bile Acids. Robert A. Quinn, Alison Vrbanac, Alexey V. Melnik, Kathryn A. Patras, Mitchell Christy, Andrew T. Nelson, Alexander Aksenov, Anupriya Tripathi, Greg Humphrey, Ricardo da Silva, Robert Bussell, Taren Thron, Mingxun Wang, Fernando Vargas, Julia M. Gauglitz, Michael J. Meehan, Orit Poulsen, Brigid S. Boland, John T. Chang, William J. Sandborn, Meerana Lim, Neha Garg, Julie Lumeng, Barbara I. Kazmierczak, Ruchi Jain, Marie Egan, Kyung E. Rhee, Gabriel G. Haddad, Dionicio Siegel, Sarkis Mazmanian, Victor Nizet, Rob Knight, Pieter C. Dorrestein. bioRxiv 654756; doi: https://doi.org/10.1101/654756
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:99619
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:13 Jan 2020 18:58
Last Modified:13 Jan 2020 18:58

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