Cell Reports (Aug 2023)
Paired microbiome and metabolome analyses associate bile acid changes with colorectal cancer progression
- Ting Fu,
- Tao Huan,
- Gibraan Rahman,
- Hui Zhi,
- Zhenjiang Xu,
- Tae Gyu Oh,
- Jian Guo,
- Sally Coulter,
- Anupriya Tripathi,
- Cameron Martino,
- Justin L. McCarville,
- Qiyun Zhu,
- Fritz Cayabyab,
- Brian Low,
- Mingxiao He,
- Shipei Xing,
- Fernando Vargas,
- Ruth T. Yu,
- Annette Atkins,
- Christopher Liddle,
- Janelle Ayres,
- Manuela Raffatellu,
- Pieter C. Dorrestein,
- Michael Downes,
- Rob Knight,
- Ronald M. Evans
Affiliations
- Ting Fu
- Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
- Tao Huan
- Department of Chemistry, UBC Faculty of Science, Vancouver Campus, Vancouver, BC V6T 1Z4, Canada
- Gibraan Rahman
- Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093, USA
- Hui Zhi
- Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA
- Zhenjiang Xu
- UCSD Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA
- Tae Gyu Oh
- Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
- Jian Guo
- Department of Chemistry, UBC Faculty of Science, Vancouver Campus, Vancouver, BC V6T 1Z4, Canada
- Sally Coulter
- Storr Liver Centre, Westmead Institute for Medical Research and Sydney Medical School, University of Sydney, Westmead, NSW 2145, Australia
- Anupriya Tripathi
- UCSD Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA
- Cameron Martino
- 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
- Justin L. McCarville
- 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
- Qiyun Zhu
- UCSD Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA
- Fritz Cayabyab
- Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
- Brian Low
- Department of Chemistry, UBC Faculty of Science, Vancouver Campus, Vancouver, BC V6T 1Z4, Canada
- Mingxiao He
- Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
- Shipei Xing
- Department of Chemistry, UBC Faculty of Science, Vancouver Campus, Vancouver, BC V6T 1Z4, Canada
- Fernando Vargas
- UCSD Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA
- Ruth T. Yu
- Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
- Annette Atkins
- Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
- Christopher Liddle
- Storr Liver Centre, Westmead Institute for Medical Research and Sydney Medical School, University of Sydney, Westmead, NSW 2145, Australia
- Janelle Ayres
- 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
- Manuela Raffatellu
- 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
- Pieter C. Dorrestein
- 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
- Michael Downes
- Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
- Rob Knight
- 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; Corresponding author
- Ronald M. Evans
- Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Corresponding author
- Journal volume & issue
-
Vol. 42,
no. 8
p. 112997
Abstract
Summary: 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.
