The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story, yet mesmerizing

Int J Cancer. 2020 Apr 1;146(7):1780-1790. doi: 10.1002/ijc.32563. Epub 2019 Jul 23.

Abstract

The prevalence of colorectal cancer (CRC) has markedly increased worldwide in the last decade. Alterations of bile acid metabolism and gut microbiota have been reported to play vital roles in intestinal carcinogenesis. About trillions of bacteria have inhabited in the human gut and maintained the balance of host metabolism. Bile acids are one of numerous metabolites that are synthesized in the liver and further metabolized by the gut microbiota, and are essential in maintaining the normal gut microbiota and lipid digestion. Multiple receptors such as FXR, GPBAR1, PXR, CAR and VDR act as sensors of bile acids have been reported. In this review, we mainly discussed interplay between bile acid metabolism and gut microbiota in intestinal carcinogenesis. We then summarized the critical role of bile acids receptors involving in CRC, and also addressed the rationale of multiple interventions for CRC management by regulating bile acids-microbiota axis such as probiotics, metformin, ursodeoxycholic acid and fecal microbiota transplantation. Thus, by targeting the bile acids-microbiota axis may provide novel therapeutic modalities in CRC prevention and treatment.

Keywords: G protein-coupled bile acid receptor 1; bile acid; colorectal cancer; farnesoid X receptor; gut microbiota.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bile Acids and Salts / metabolism
  • Biological Therapy
  • Biomarkers
  • Cell Transformation, Neoplastic / metabolism*
  • Colorectal Neoplasms / etiology
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy
  • Dysbiosis
  • Gastrointestinal Microbiome* / drug effects
  • Humans
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / microbiology*
  • Intestinal Mucosa / pathology
  • Metabolic Networks and Pathways / drug effects
  • Molecular Targeted Therapy
  • Protein Binding
  • Receptors, Cytoplasmic and Nuclear / metabolism

Substances

  • Bile Acids and Salts
  • Biomarkers
  • Receptors, Cytoplasmic and Nuclear