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

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 LiddleJanelle Ayres, Manuela Raffatellu, Pieter C. Dorrestein, Michael Downes, Rob Knight, Ronald M. Evans

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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.

Original language	English (US)
Article number	112997
Journal	Cell Reports
Volume	42
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2023.112997
State	Published - Aug 29 2023
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.celrep.2023.112997

Cite this

Fu, T., Huan, T., Rahman, G., Zhi, H., Xu, Z., Oh, T. G., Guo, J., Coulter, S., Tripathi, A., Martino, C., McCarville, J. L., Zhu, Q., Cayabyab, F., Low, B., He, M., Xing, S., Vargas, F., Yu, R. T., Atkins, A., ... Evans, R. M. (2023). Paired microbiome and metabolome analyses associate bile acid changes with colorectal cancer progression. Cell Reports, 42(8), Article 112997. https://doi.org/10.1016/j.celrep.2023.112997

Fu, T, Huan, T, Rahman, G, Zhi, H, Xu, Z, Oh, TG, Guo, J, Coulter, S, Tripathi, A, Martino, C, McCarville, JL, Zhu, Q, Cayabyab, F, Low, B, He, M, Xing, S, Vargas, F, Yu, RT, Atkins, A, Liddle, C, Ayres, J, Raffatellu, M, Dorrestein, PC, Downes, M, Knight, R & Evans, RM 2023, 'Paired microbiome and metabolome analyses associate bile acid changes with colorectal cancer progression', Cell Reports, vol. 42, no. 8, 112997. https://doi.org/10.1016/j.celrep.2023.112997

@article{29ff2680f11749969e140e7ab11e0e83,

title = "Paired microbiome and metabolome analyses associate bile acid changes with colorectal cancer progression",

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",

author = "Ting Fu and Tao Huan and Gibraan Rahman and Hui Zhi and Zhenjiang Xu and Oh, {Tae Gyu} and Jian Guo and Sally Coulter and Anupriya Tripathi and Cameron Martino and McCarville, {Justin L.} and Qiyun Zhu and Fritz Cayabyab and Brian Low and Mingxiao He and Shipei Xing and Fernando Vargas and Yu, {Ruth T.} and Annette Atkins and Christopher Liddle and Janelle Ayres and Manuela Raffatellu and Dorrestein, {Pieter C.} and Michael Downes and Rob Knight and Evans, {Ronald M.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

month = aug,

day = "29",

doi = "10.1016/j.celrep.2023.112997",

language = "English (US)",

volume = "42",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "8",

}

TY - JOUR

T1 - Paired microbiome and metabolome analyses associate bile acid changes with colorectal cancer progression

AU - Fu, Ting

AU - Huan, Tao

AU - Rahman, Gibraan

AU - Zhi, Hui

AU - Xu, Zhenjiang

AU - Oh, Tae Gyu

AU - Guo, Jian

AU - Coulter, Sally

AU - Tripathi, Anupriya

AU - Martino, Cameron

AU - McCarville, Justin L.

AU - Zhu, Qiyun

AU - Cayabyab, Fritz

AU - Low, Brian

AU - He, Mingxiao

AU - Xing, Shipei

AU - Vargas, Fernando

AU - Yu, Ruth T.

AU - Atkins, Annette

AU - Liddle, Christopher

AU - Ayres, Janelle

AU - Raffatellu, Manuela

AU - Dorrestein, Pieter C.

AU - Downes, Michael

AU - Knight, Rob

AU - Evans, Ronald M.

PY - 2023/8/29

Y1 - 2023/8/29

N2 - 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.

AB - 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.

KW - CP: Cancer

KW - CP: Microbiology

KW - bile acids

KW - colorectal cancer

KW - conjugated bile acids

KW - high-fat diet

KW - metabolome

KW - microbiome

UR - http://www.scopus.com/inward/record.url?scp=85169502971&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85169502971&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2023.112997

DO - 10.1016/j.celrep.2023.112997

M3 - Article

C2 - 37611587

AN - SCOPUS:85169502971

SN - 2211-1247

VL - 42

JO - Cell Reports

JF - Cell Reports

IS - 8

M1 - 112997

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this