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Global chemical effects of the microbiome include new bile-acid conjugations.
Quinn, Robert A; Melnik, Alexey V; Vrbanac, Alison; Fu, Ting; Patras, Kathryn A; Christy, Mitchell P; Bodai, Zsolt; Belda-Ferre, Pedro; Tripathi, Anupriya; Chung, Lawton K; Downes, Michael; Welch, Ryan D; Quinn, Melissa; Humphrey, Greg; Panitchpakdi, Morgan; Weldon, Kelly C; Aksenov, Alexander; da Silva, Ricardo; Avila-Pacheco, Julian; Clish, Clary; Bae, Sena; Mallick, Himel; Franzosa, Eric A; Lloyd-Price, Jason; Bussell, Robert; Thron, Taren; Nelson, Andrew T; Wang, Mingxun; Leszczynski, Eric; Vargas, Fernando; Gauglitz, Julia M; Meehan, Michael J; Gentry, Emily; Arthur, Timothy D; Komor, Alexis C; Poulsen, Orit; Boland, Brigid S; Chang, John T; Sandborn, William J; Lim, Meerana; Garg, Neha; Lumeng, Julie C; Xavier, Ramnik J; Kazmierczak, Barbara I; Jain, Ruchi; Egan, Marie; Rhee, Kyung E; Ferguson, David; Raffatellu, Manuela; Vlamakis, Hera.
Affiliation
  • Quinn RA; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA.
  • Melnik AV; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA.
  • Vrbanac A; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA.
  • Fu T; Department of Pediatrics, University of California San Diego, San Diego, CA, USA.
  • Patras KA; Gene Expression Laboratory, Salk Institute for Biological Studies, San Diego, CA, USA.
  • Christy MP; Department of Pediatrics, University of California San Diego, San Diego, CA, USA.
  • Bodai Z; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA.
  • Belda-Ferre P; Department of Chemistry and Biochemistry, University of California San Diego, San Diego, CA, USA.
  • Tripathi A; Department of Pediatrics, University of California San Diego, San Diego, CA, USA.
  • Chung LK; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA.
  • Downes M; Department of Pediatrics, University of California San Diego, San Diego, CA, USA.
  • Welch RD; Department of Pediatrics, University of California San Diego, San Diego, CA, USA.
  • Quinn M; Gene Expression Laboratory, Salk Institute for Biological Studies, San Diego, CA, USA.
  • Humphrey G; Gene Expression Laboratory, Salk Institute for Biological Studies, San Diego, CA, USA.
  • Panitchpakdi M; Department of Kinesiology, Michigan State University, East Lansing, MI, USA.
  • Weldon KC; Department of Pediatrics, University of California San Diego, San Diego, CA, USA.
  • Aksenov A; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA.
  • da Silva R; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA.
  • Avila-Pacheco J; UCSD Center for Microbiome Innovation, University of California San Diego, San Diego, CA, USA.
  • Clish C; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA.
  • Bae S; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA.
  • Mallick H; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Franzosa EA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Lloyd-Price J; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
  • Bussell R; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
  • Thron T; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Nelson AT; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
  • Wang M; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Leszczynski E; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
  • Vargas F; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Gauglitz JM; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
  • Meehan MJ; Department of Radiology, University of California San Diego, San Diego, CA, USA.
  • Gentry E; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
  • Arthur TD; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA.
  • Komor AC; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA.
  • Poulsen O; Department of Kinesiology, Michigan State University, East Lansing, MI, USA.
  • Boland BS; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA.
  • Chang JT; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA.
  • Sandborn WJ; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA.
  • Lim M; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA.
  • Garg N; Department of Pediatrics, University of California San Diego, San Diego, CA, USA.
  • Lumeng JC; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Xavier RJ; Department of Chemistry and Biochemistry, University of California San Diego, San Diego, CA, USA.
  • Kazmierczak BI; Department of Pediatrics, University of California San Diego, San Diego, CA, USA.
  • Jain R; Division of Gastroenterology, Department of Medicine, University of California San Diego, San Diego, CA, USA.
  • Egan M; Division of Gastroenterology, Department of Medicine, University of California San Diego, San Diego, CA, USA.
  • Rhee KE; Division of Gastroenterology, Department of Medicine, University of California San Diego, San Diego, CA, USA.
  • Ferguson D; Department of Pediatrics, University of California San Diego, San Diego, CA, USA.
  • Raffatellu M; School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA.
  • Vlamakis H; Emory-Children's Cystic Fibrosis Center, Atlanta, GA, USA.
Nature ; 579(7797): 123-129, 2020 03.
Article in En | MEDLINE | ID: mdl-32103176
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Bile Acids and Salts / Metabolomics / Microbiota Limits: Animals / Humans Language: En Journal: Nature Year: 2020 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Bile Acids and Salts / Metabolomics / Microbiota Limits: Animals / Humans Language: En Journal: Nature Year: 2020 Type: Article Affiliation country: United States