Apple proanthocyanidins do not reduce the induction of preneoplastic lesions in the colon of rats associated with human microbiota

Since the gut microbiota metabolizes various dietary constituents unabsorbed by the small intestine and modulates colon function, it plays an essential role in colon carcinogenesis. First, we have developed a model of human microbiota-associated rats (HMA), fed a human-type diet and injected with 1-2,dimethylhydrazine (DMH). We observed that the number and size of DMH-induced aberrant crypt foci (ACF) were significantly higher in HMA rats than in germ-free or conventional rats. Second, we used this model to assess the protective effect of an apple proanthocyanidin-rich extract (APE) on colon carcinogenesis. In this model, ACF number and multiplicity were not reduced by APE at 0.001% and 0.01% in drinking water. They were higher with APE 0.1% than with APE 0.01%. Therefore, the cross-talk between human microbiota and the colon epithelium should be taken into account in carcinogenesis models. Moreover, attention should be paid prior to using proanthocyanidin extracts as dietary supplements for humans