Haem iron reshapes colonic luminal environment: impact on mucosal homeostasis and microbiome through aldehyde formation

Microbiome. 2019 May 6;7(1):72. doi: 10.1186/s40168-019-0685-7.

Abstract

Background: The World Health Organization classified processed and red meat consumption as "carcinogenic" and "probably carcinogenic", respectively, to humans. Haem iron from meat plays a role in the promotion of colorectal cancer in rodent models, in association with enhanced luminal lipoperoxidation and subsequent formation of aldehydes. Here, we investigated the short-term effects of this haem-induced lipoperoxidation on mucosal and luminal gut homeostasis including microbiome in F344 male rats fed with a haem-enriched diet (1.5 μmol/g) 14-21 days.

Results: Changes in permeability, inflammation, and genotoxicity observed in the mucosal colonic barrier correlated with luminal haem and lipoperoxidation markers. Trapping of luminal haem-induced aldehydes normalised cellular genotoxicity, permeability, and ROS formation on a colon epithelial cell line. Addition of calcium carbonate (2%) to the haem-enriched diet allowed the luminal haem to be trapped in vivo and counteracted these haem-induced physiological traits. Similar covariations of faecal metabolites and bacterial taxa according to haem-induced lipoperoxidation were identified.

Conclusions: This integrated approach provides an overview of haem-induced modulations of the main actors in the colonic barrier. All alterations were closely linked to haem-induced lipoperoxidation, which is associated with red meat-induced colorectal cancer risk.

Keywords: Barrier function; Dysbiosis; Lipoperoxidation; Meat; Metabolites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / metabolism*
  • Animals
  • Colon / metabolism*
  • Heme / administration & dosage*
  • Heme / metabolism
  • Homeostasis
  • Inflammation
  • Intestinal Mucosa / metabolism*
  • Iron / metabolism*
  • Lipid Peroxides / metabolism
  • Male
  • Microbiota*
  • Mutagenicity Tests
  • Rats
  • Rats, Inbred F344

Substances

  • Aldehydes
  • Lipid Peroxides
  • Heme
  • Iron