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

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 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 and Pieter C. Dorrestein ()
Additional contact information
Robert A. Quinn: University of California San Diego
Alexey V. Melnik: University of California San Diego
Alison Vrbanac: University of California San Diego
Ting Fu: Salk Institute for Biological Studies
Kathryn A. Patras: University of California San Diego
Mitchell P. Christy: University of California San Diego
Zsolt Bodai: University of California San Diego
Pedro Belda-Ferre: University of California San Diego
Anupriya Tripathi: University of California San Diego
Lawton K. Chung: University of California San Diego
Michael Downes: Salk Institute for Biological Studies
Ryan D. Welch: Salk Institute for Biological Studies
Melissa Quinn: Michigan State University
Greg Humphrey: University of California San Diego
Morgan Panitchpakdi: University of California San Diego
Kelly C. Weldon: University of California San Diego
Alexander Aksenov: University of California San Diego
Ricardo Silva: University of California San Diego
Julian Avila-Pacheco: Broad Institute of MIT and Harvard
Clary Clish: Broad Institute of MIT and Harvard
Sena Bae: Harvard T. H. Chan School of Public Health
Himel Mallick: Broad Institute of MIT and Harvard
Eric A. Franzosa: Broad Institute of MIT and Harvard
Jason Lloyd-Price: Broad Institute of MIT and Harvard
Robert Bussell: University of California San Diego
Taren Thron: California Institute of Technology
Andrew T. Nelson: University of California San Diego
Mingxun Wang: University of California San Diego
Eric Leszczynski: Michigan State University
Fernando Vargas: University of California San Diego
Julia M. Gauglitz: University of California San Diego
Michael J. Meehan: University of California San Diego
Emily Gentry: University of California San Diego
Timothy D. Arthur: University of California San Diego
Alexis C. Komor: 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
Ramnik J. Xavier: Broad Institute of MIT and Harvard
Barbara I. Kazmierczak: Yale School of Medicine
Ruchi Jain: Yale School of Medicine
Marie Egan: Yale School of Medicine
Kyung E. Rhee: University of California San Diego
David Ferguson: Michigan State University
Manuela Raffatellu: University of California San Diego
Hera Vlamakis: Broad Institute of MIT and Harvard
Gabriel G. Haddad: University of California San Diego
Dionicio Siegel: University of California San Diego
Curtis Huttenhower: Broad Institute of MIT and Harvard
Sarkis K. Mazmanian: California Institute of Technology
Ronald M. Evans: Salk Institute for Biological Studies
Victor Nizet: University of California San Diego
Rob Knight: University of California San Diego
Pieter C. Dorrestein: University of California San Diego

Nature, 2020, vol. 579, issue 7797, 123-129

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41586-020-2047-9

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