Gut Microbiota-Mediated Inflammation and Gut Permeability in Patients with Obesity and Colorectal Cancer

Int J Mol Sci. 2020 Sep 16;21(18):6782. doi: 10.3390/ijms21186782.

Abstract

Obesity is considered an important factor that increases the risk of colorectal cancer (CRC). So far, the association of gut microbiota with both obesity and cancer has been described independently. Nevertheless, a specific obesity-related microbial profile linked to CRC development has not been identified. The aim of this study was to determine the gut microbiota composition in fecal samples from CRC patients with (OB-CRC) and without obesity (L-CRC) compared to the microbiota profile present in non-obese healthy controls (L-HC), in order to unravel the possible relationship between gut microbiota and microbial-derived metabolite trimethylamine N-oxide (TMAO), the inflammatory status, and the intestinal permeability in the context of obesity-associated CRC. The presence of obesity does not induce significant changes in the diversity and richness of intestinal bacteria of CRC patients. Nevertheless, OB-CRC patients display a specific gut microbiota profile characterized by a reduction in butyrate-producing bacteria and an overabundance of opportunistic pathogens, which in turn could be responsible, at least in part, for the higher levels of proinflammatory cytokine IL-1β, the deleterious bacterial metabolite TMAO, and gut permeability found in these patients. These results suggest a possible role of obesity-related gut microbiota in the development of CRC, which could give new clues for the design of new diagnostic tools for CRC prevention.

Keywords: TMAO; colorectal cancer; gut microbiota; gut permeability; inflammation; obesity.

MeSH terms

  • Aged
  • Bacteria / classification
  • Bacteria / genetics
  • Bacteria / isolation & purification*
  • Bacteria / metabolism
  • Biomarkers
  • Body Mass Index
  • Colorectal Neoplasms / etiology
  • Colorectal Neoplasms / microbiology*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / physiopathology
  • Dysbiosis / complications
  • Dysbiosis / microbiology*
  • Dysbiosis / pathology
  • Dysbiosis / physiopathology
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome / physiology*
  • Haptoglobins
  • Humans
  • Inflammation / blood
  • Inflammation / microbiology*
  • Inflammation Mediators / blood
  • Interleukins / blood
  • Male
  • Metagenome
  • Methylamines / adverse effects
  • Methylamines / blood
  • Middle Aged
  • Obesity / metabolism
  • Obesity / microbiology*
  • Obesity / pathology
  • Obesity / physiopathology
  • Permeability
  • Protein Precursors / blood

Substances

  • Biomarkers
  • Haptoglobins
  • Inflammation Mediators
  • Interleukins
  • Methylamines
  • Protein Precursors
  • zonulin
  • trimethyloxamine