Race-dependent association of sulfidogenic bacteria with colorectal cancer

Gut. 2017 Nov;66(11):1983-1994. doi: 10.1136/gutjnl-2016-313321. Epub 2017 Feb 2.

Abstract

Objective: Colorectal cancer (CRC) incidence is higher in African Americans (AAs) compared with non-Hispanic whites (NHWs). A diet high in animal protein and fat is an environmental risk factor for CRC development. The intestinal microbiota is postulated to modulate the effects of diet in promoting or preventing CRC. Hydrogen sulfide, produced by autochthonous sulfidogenic bacteria, triggers proinflammatory pathways and hyperproliferation, and is genotoxic. We hypothesised that sulfidogenic bacterial abundance in colonic mucosa may be an environmental CRC risk factor that distinguishes AA and NHW.

Design: Colonic biopsies from uninvolved or healthy mucosa from CRC cases and tumour-free controls were collected prospectively from five medical centres in Chicago for association studies. Sulfidogenic bacterial abundance in uninvolved colonic mucosa of AA and NHW CRC cases was compared with normal mucosa of AA and NHW controls. In addition, 16S rDNA sequencing was performed in AA cases and controls. Correlations were examined among bacterial targets, race, disease status and dietary intake.

Results: AAs harboured a greater abundance of sulfidogenic bacteria compared with NHWs regardless of disease status. Bilophila wadsworthia-specific dsrA was more abundant in AA cases than controls. Linear discriminant analysis of 16S rRNA gene sequences revealed five sulfidogenic genera that were more abundant in AA cases. Fat and protein intake and daily servings of meat were significantly higher in AAs compared with NHWs, and multiple dietary components correlated with a higher abundance of sulfidogenic bacteria.

Conclusions: These results implicate sulfidogenic bacteria as a potential environmental risk factor contributing to CRC development in AAs.

Keywords: COLONIC MICROFLORA; COLORECTAL CANCER; HYDROGEN SULPHIDE.

Publication types

  • Multicenter Study

MeSH terms

  • Adenocarcinoma / ethnology
  • Adenocarcinoma / etiology
  • Adenocarcinoma / microbiology*
  • Adult
  • Aged
  • Black or African American*
  • Case-Control Studies
  • Chicago
  • Colon / microbiology*
  • Colorectal Neoplasms / ethnology
  • Colorectal Neoplasms / etiology
  • Colorectal Neoplasms / microbiology*
  • Diet / adverse effects
  • Dietary Fats / adverse effects
  • Dietary Proteins / adverse effects
  • Female
  • Health Status Disparities
  • Humans
  • Intestinal Mucosa / microbiology*
  • Male
  • Middle Aged
  • Prospective Studies
  • Real-Time Polymerase Chain Reaction
  • Risk Factors
  • Sulfur-Reducing Bacteria / isolation & purification*
  • White People*

Substances

  • Dietary Fats
  • Dietary Proteins