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

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Martin, Océane | Olier, Maïwenn | Ellero-Simatos, Sandrine | Naud, Nathalie | Dupuy, Jacques | Huc, Laurence | Taché, Sylviane | Graillot, Vanessa | Lévêque, Mathilde | Bézirard, Valérie | Héliès-Toussaint, Cécile | Blas-Y-Estrada, Florence | Tondereau, Valérie | Lippi, Yannick | Naylies, Claire | Peyriga, Lindsay | Canlet, Cécile | Davila, Anne-Marie | Blachier, François | Ferrier, Laurent | Boutet-Robinet, Elisa | Guéraud, Françoise | Theodorou, Vassilia | Pierre, Fabrice H.F.

Edité par CCSD ; BioMed Central -

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.

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