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

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 colorectalcancer in rodent models, in association with enhanced luminal lipoperoxidation and subsequent formation ofaldehydes. 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 correlatedwith luminal haem and lipoperoxidation markers. Trapping of luminal haem-induced aldehydes normalised cellulargenotoxicity, 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-inducedphysiological traits. Similar covariations of faecal metabolites and bacterial taxa according to haem-inducedlipoperoxidation were identified.Conclusions: This integrated approach provides an overview of haem-induced modulations of the mainactors in the colonic barrier. All alterations were closely linked to haem-induced lipoperoxidation, which isassociated with red meat-induced colorectal cancer risk