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

• Published in: Cell reports (Cambridge) 2023-08, Vol.42 (8), p.112997-112997, Article 112997
• Main Authors: Fu, Ting, Huan, Tao, Rahman, Gibraan, Zhi, Hui, Xu, Zhenjiang, Oh, Tae Gyu, Guo, Jian, Coulter, Sally, Tripathi, Anupriya, Martino, Cameron, McCarville, Justin L., Zhu, Qiyun, Cayabyab, Fritz, Low, Brian, He, Mingxiao, Xing, Shipei, Vargas, Fernando, Yu, Ruth T., Atkins, Annette, Liddle, Christopher, Ayres, Janelle, Raffatellu, Manuela, Dorrestein, Pieter C., Downes, Michael, Knight, Rob, Evans, Ronald M.
• Format: Article
• Language: English
• Subjects: Animals; bile acids; Bile Acids and Salts; colorectal cancer; Colorectal Neoplasms; conjugated bile acids; CP: Cancer; CP: Microbiology; Gastrointestinal Microbiome; high-fat diet; Metabolome; Mice; microbiome; Microbiota
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112997

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. [Display omitted] •Microbiome and metabolome changes during colorectal cancer (CRC) progression•High-fat diet is a dominant determinant of cecal microbiome in CRC-susceptible APCmin/+ mice•Microbially conjugated bile acids increase with high-fat diet Fu et al. identify high-fat diet as a dominant determinant of the cecal microbiome and metabolome in a mouse model of colorectal cancer and implicate microbially conjugated bile acids as potential drivers of disease progression.