16S rRNA of Mucosal Colon Microbiome and CCL2 Circulating Levels Are Potential Biomarkers in Colorectal Cancer

Int J Mol Sci. 2021 Oct 4;22(19):10747. doi: 10.3390/ijms221910747.

Abstract

Colorectal cancer (CRC) is one of the most common malignancies in the Western world and intestinal dysbiosis might contribute to its pathogenesis. The mucosal colon microbiome and C-C motif chemokine 2 (CCL2) were investigated in 20 healthy controls (HC) and 20 CRC patients using 16S rRNA sequencing and immunoluminescent assay, respectively. A total of 10 HC subjects were classified as overweight/obese (OW/OB_HC) and 10 subjects were normal weight (NW_HC); 15 CRC patients were classified as OW/OB_CRC and 5 patients were NW_CRC. Results: Fusobacterium nucleatum and Escherichia coli were more abundant in OW/OB_HC than in NW_HC microbiomes. Globally, Streptococcus intermedius, Gemella haemolysans, Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli were significantly increased in CRC patient tumor/lesioned tissue (CRC_LT) and CRC patient unlesioned tissue (CRC_ULT) microbiomes compared to HC microbiomes. CCL2 circulating levels were associated with tumor presence and with the abundance of Fusobacterium nucleatum, Bacteroides fragilis and Gemella haemolysans. Our data suggest that mucosal colon dysbiosis might contribute to CRC pathogenesis by inducing inflammation. Notably, Fusobacterium nucleatum, which was more abundant in the OW/OB_HC than in the NW_HC microbiomes, might represent a putative link between obesity and increased CRC risk.

Keywords: 16S rRNA gene; CCL2 [chemokine (C-C motif) ligand 2]; colorectal cancer; mucosal colon microbiome; obesity.

MeSH terms

  • Aged
  • Bacteria / classification
  • Bacteria / genetics*
  • Bacteria / growth & development
  • Bacteria / isolation & purification
  • Biomarkers / analysis*
  • Case-Control Studies
  • Chemokine CCL2 / blood*
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / microbiology
  • Female
  • Gastrointestinal Microbiome*
  • Humans
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology*
  • Male
  • Middle Aged
  • RNA, Ribosomal, 16S / analysis
  • RNA, Ribosomal, 16S / genetics*

Substances

  • Biomarkers
  • CCL2 protein, human
  • Chemokine CCL2
  • RNA, Ribosomal, 16S