Global chemical effects of the microbiome include new bile-acid conjugations View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-02-26

AUTHORS

Robert A. Quinn, Alexey V. Melnik, Alison Vrbanac, Ting Fu, Kathryn A. Patras, Mitchell P. Christy, Zsolt Bodai, Pedro Belda-Ferre, Anupriya Tripathi, Lawton K. Chung, Michael Downes, Ryan D. Welch, Melissa Quinn, Greg Humphrey, Morgan Panitchpakdi, Kelly C. Weldon, Alexander Aksenov, Ricardo da Silva, Julian Avila-Pacheco, Clary Clish, Sena Bae, Himel Mallick, Eric A. Franzosa, Jason Lloyd-Price, Robert Bussell, Taren Thron, Andrew T. Nelson, Mingxun Wang, Eric Leszczynski, Fernando Vargas, Julia M. Gauglitz, Michael J. Meehan, Emily Gentry, Timothy D. Arthur, Alexis C. Komor, Orit Poulsen, Brigid S. Boland, John T. Chang, William J. Sandborn, Meerana Lim, Neha Garg, Julie C. Lumeng, Ramnik J. Xavier, Barbara I. Kazmierczak, Ruchi Jain, Marie Egan, Kyung E. Rhee, David Ferguson, Manuela Raffatellu, Hera Vlamakis, Gabriel G. Haddad, Dionicio Siegel, Curtis Huttenhower, Sarkis K. Mazmanian, Ronald M. Evans, Victor Nizet, Rob Knight, Pieter C. Dorrestein

ABSTRACT

A mosaic of cross-phylum chemical interactions occurs between all metazoans and their microbiomes. A number of molecular families that are known to be produced by the microbiome have a marked effect on the balance between health and disease1–9. Considering the diversity of the human microbiome (which numbers over 40,000 operational taxonomic units10), the effect of the microbiome on the chemistry of an entire animal remains underexplored. Here we use mass spectrometry informatics and data visualization approaches11–13 to provide an assessment of the effects of the microbiome on the chemistry of an entire mammal by comparing metabolomics data from germ-free and specific-pathogen-free mice. We found that the microbiota affects the chemistry of all organs. This included the amino acid conjugations of host bile acids that were used to produce phenylalanocholic acid, tyrosocholic acid and leucocholic acid, which have not previously been characterized despite extensive research on bile-acid chemistry14. These bile-acid conjugates were also found in humans, and were enriched in patients with inflammatory bowel disease or cystic fibrosis. These compounds agonized the farnesoid X receptor in vitro, and mice gavaged with the compounds showed reduced expression of bile-acid synthesis genes in vivo. Further studies are required to confirm whether these compounds have a physiological role in the host, and whether they contribute to gut diseases that are associated with microbiome dysbiosis. More... »

PAGES

123-129

Journal

TITLE

Nature

ISSUE

7797

VOLUME

579

Author Affiliations

  • Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA
  • Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA
  • Department of Pediatrics, University of California San Diego, San Diego, CA, USA
  • Gene Expression Laboratory, Salk Institute for Biological Studies, San Diego, CA, USA
  • Department of Chemistry and Biochemistry, University of California San Diego, San Diego, CA, USA
  • Department of Kinesiology, Michigan State University, East Lansing, MI, USA
  • UCSD Center for Microbiome Innovation, University of California San Diego, San Diego, CA, USA
  • Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA
  • Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA
  • Department of Radiology, University of California San Diego, San Diego, CA, USA
  • Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
  • Division of Gastroenterology, Department of Medicine, University of California San Diego, San Diego, CA, USA
  • Emory-Children’s Cystic Fibrosis Center, Atlanta, GA, USA
  • Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA
  • Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA
  • Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA
  • Howard Hughes Medical Institute, The Salk Institute for Biological Studies, San Diego, CA, USA
  • Department of Engineering, University of California San Diego, San Diego, CA, USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41586-020-2047-9

    DOI

    http://dx.doi.org/10.1038/s41586-020-2047-9

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1125136854

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/32103176


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