Administration of Bifidobacterium bifidum CGMCC 15068 modulates gut microbiota and metabolome in azoxymethane (AOM)/dextran sulphate sodium (DSS)-induced colitis-associated colon cancer (CAC) in mice

Appl Microbiol Biotechnol. 2020 Jul;104(13):5915-5928. doi: 10.1007/s00253-020-10621-z. Epub 2020 May 4.

Abstract

The gut microbiota plays an important role in colorectal cancer (CRC), and the use of probiotics might be a promising intervention method. The aim of our study was to investigate the beneficial effect of Bifidobacterium bifidum CGMCC 15068 on an azoxymethane (AOM)/dextran sulphate sodium (DSS)-induced colitis-associated CRC (CAC) mouse model. CAC was induced by an intra-peritoneal injection of AOM (10 mg/kg) and three 7-day cycles of 2% DSS in drinking water with a 14-day recovery period between two consecutive DSS administrations. B. bifidum CGMCC 15068 (3 × 109 CFU/mL) was gavaged once daily during the recovery period. Then, the faecal microbial composition and metabolome were profiled using the 16S rRNA sequencing technology and gas chromatography-mass spectrometry (GC-MS), respectively. The administration of B. bifidum CGMCC 15068 attenuated tumourigenesis in the CAC mouse model. In addition, B. bifidum CGMCC 15068 pre-treatment increased the relative abundance of Akkermansia, Desulfovibrionaceae, Romboutsia, Turicibacter, Verrucomicrobiaceae, Ruminococcaceae_UCG_013, Lachnospiraceae_UCG_004, and Lactobacillus. Meanwhile, B. bifidum CGMCC 15068 altered metabolites involved in the citrate cycle (TCA cycle), glycolysis, butyrate metabolism, fatty acid biosynthesis, and galactose metabolism. Several significant correlations were identified between the differentially abundant microbes and metabolites. These findings supported the beneficial role of B. bifidum CGMCC 15068 in intestinal health by modulating dysbiosis and the gut metabolic profile. The manipulation of the gut microbial composition using probiotics might be a promising prevention strategy for CRC. Long-term and large-scale clinical trials are warranted for the potential clinical applications of this strategy in the future.

Keywords: Bifidobacterium bifidum CGMCC 15068; Colorectal cancer; Gut microbiota; Metabolome.

MeSH terms

  • Animals
  • Azoxymethane / toxicity
  • Bifidobacterium bifidum / physiology*
  • Carcinogenesis / drug effects
  • Colitis-Associated Neoplasms / chemically induced
  • Colitis-Associated Neoplasms / drug therapy*
  • Colitis-Associated Neoplasms / pathology
  • Dextran Sulfate / toxicity
  • Disease Models, Animal
  • Feces / chemistry
  • Feces / microbiology
  • Gastrointestinal Microbiome / drug effects*
  • Male
  • Metabolome / drug effects*
  • Mice
  • Mice, Inbred C57BL
  • Probiotics / administration & dosage*
  • Probiotics / pharmacology

Substances

  • Dextran Sulfate
  • Azoxymethane