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

doi:10.1016/j.celrep.2023.112997

Paired microbiome and metabolome analyses associate bile acid changes with colorectal cancer progression

Cell Rep. 2023 Aug 29;42(8):112997. doi: 10.1016/j.celrep.2023.112997. Epub 2023 Aug 22.

Authors

Ting Fu¹, Tao Huan², Gibraan Rahman³, Hui Zhi⁴, Zhenjiang Xu⁵, Tae Gyu Oh¹, Jian Guo², Sally Coulter⁶, Anupriya Tripathi⁵, Cameron Martino⁷, Justin L McCarville⁸, Qiyun Zhu⁵, Fritz Cayabyab¹, Brian Low², Mingxiao He¹, Shipei Xing², Fernando Vargas⁵, Ruth T Yu¹, Annette Atkins¹, Christopher Liddle⁶, Janelle Ayres⁸, Manuela Raffatellu⁹, Pieter C Dorrestein¹⁰, Michael Downes¹, Rob Knight¹¹, Ronald M Evans¹²

Affiliations

¹ Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
² Department of Chemistry, UBC Faculty of Science, Vancouver Campus, Vancouver, BC V6T 1Z4, Canada.
³ Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093, USA.
⁴ Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.
⁵ UCSD Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA.
⁶ Storr Liver Centre, Westmead Institute for Medical Research and Sydney Medical School, University of Sydney, Westmead, NSW 2145, Australia.
⁷ 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.
⁸ 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.
⁹ 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.
¹⁰ 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.
¹¹ 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.
¹² Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: evans@salk.edu.

Abstract

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.

Keywords: CP: Cancer; CP: Microbiology; bile acids; colorectal cancer; conjugated bile acids; high-fat diet; metabolome; microbiome.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bile Acids and Salts
Colorectal Neoplasms*
Gastrointestinal Microbiome*
Metabolome
Mice
Microbiota*

Substances

Bile Acids and Salts

Abstract

Publication types

MeSH terms

Substances

Grants and funding