Abstract
BackgroundThe 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.ResultsChanges 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.ConclusionsThis 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.
Highlights
The World Health Organization classified processed and red meat consumption as “carcinogenic” and “probably carcinogenic”, respectively, to humans
We previously showed that haem iron is the major actor in meat-induced promotion of colorectal cancer without additive or synergistic effects of heterocyclic amines and endogenous N-nitroso compounds [4]
Haem iron-induced lipoperoxidation is associated with increased markers of colonic inflammation, genotoxicity, and permeability in vivo The addition of dietary haem for 21 days significantly increased luminal faecal haem compared to rats fed with the CON and Ca diets (P < 0.0001 and P = 0.001, respectively, Fig. 1a)
Summary
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. The promotion of colon carcinogenesis by red meat consumption is at least in part explained by haem-induced lipoperoxidation [4, 6,7,8]. Dietary haem iron catalyses lipid oxidation, leading to the production of alpha-beta unsaturated aldehydes (alkenals), such as 4-hydroxynonenal (HNE) from n-6 fatty acids [9]. This formation of aldehydes correlates with the promotion of preneoplastic lesions in rats and of adenoma in Min mice [4]. Though the effects of haem or aldehydes have already been studied independently on microbiota or colon epithelial cells, to the best of our knowledge, no in vivo study has investigated the short-term effect of dietary haem iron and subsequently formed aldehydes on gut barrier actors as a whole
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