Paired microbiome and metabolome analyses associate bile acid changes with colorectal cancer progression.
Autor: | Fu T; Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Huan T; Department of Chemistry, UBC Faculty of Science, Vancouver Campus, Vancouver, BC V6T 1Z4, Canada., Rahman G; Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093, USA., Zhi H; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA., Xu Z; UCSD Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA., Oh TG; Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Guo J; Department of Chemistry, UBC Faculty of Science, Vancouver Campus, Vancouver, BC V6T 1Z4, Canada., Coulter S; Storr Liver Centre, Westmead Institute for Medical Research and Sydney Medical School, University of Sydney, Westmead, NSW 2145, Australia., Tripathi A; UCSD Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA., Martino C; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA; UCSD Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA., McCarville JL; Molecular and Systems Physiology Laboratory, Gene Expression Laboratory, NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Zhu Q; UCSD Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA., Cayabyab F; Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Low B; Department of Chemistry, UBC Faculty of Science, Vancouver Campus, Vancouver, BC V6T 1Z4, Canada., He M; Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Xing S; Department of Chemistry, UBC Faculty of Science, Vancouver Campus, Vancouver, BC V6T 1Z4, Canada., Vargas F; UCSD Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA., Yu RT; Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Atkins A; Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Liddle C; Storr Liver Centre, Westmead Institute for Medical Research and Sydney Medical School, University of Sydney, Westmead, NSW 2145, Australia., Ayres J; Molecular and Systems Physiology Laboratory, Gene Expression Laboratory, NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Raffatellu M; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA; UCSD Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA; Chiba University-UC San Diego Center for Mucosal Immunity, Allergy, and Vaccines (CU-UCSD cMAV), La Jolla, CA 92093, USA., Dorrestein PC; UCSD Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA; Department of Engineering, University of California, San Diego, La Jolla, CA 92093, USA; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA., Downes M; Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Knight R; Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093, USA; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA; UCSD Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA; Department of Engineering, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: robknight@eng.ucsd.edu., Evans RM; Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: evans@salk.edu. |
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Jazyk: | angličtina |
Zdroj: | Cell reports [Cell Rep] 2023 Aug 29; Vol. 42 (8), pp. 112997. Date of Electronic Publication: 2023 Aug 22. |
DOI: | 10.1016/j.celrep.2023.112997 |
Abstrakt: | Colorectal cancer (CRC) is driven by genomic alterations in concert with dietary influences, with the gut microbiome implicated as an effector in disease development and progression. While meta-analyses have provided mechanistic insight into patients with CRC, study heterogeneity has limited causal associations. Using multi-omics studies on genetically controlled cohorts of mice, we identify diet as the major driver of microbial and metabolomic differences, with reductions in α diversity and widespread changes in cecal metabolites seen in high-fat diet (HFD)-fed mice. In addition, non-classic amino acid conjugation of the bile acid cholic acid (AA-CA) increased with HFD. We show that AA-CAs impact intestinal stem cell growth and demonstrate that Ileibacterium valens and Ruminococcus gnavus are able to synthesize these AA-CAs. This multi-omics dataset implicates diet-induced shifts in the microbiome and the metabolome in disease progression and has potential utility in future diagnostic and therapeutic developments. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
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