Enterotoxic potential of dietary cholesterol autoxidation products

In both Western and Westernized diets, together with a relatively high amount of cholesterol, a variable amount of its oxidized metabolites, oxysterols, are consistently taken up. These oxysterols, mostly of non-enzymatic origin, are produced during sterol autoxidation in foodstuff manufacturing and storage. Objective: analysis of the potential enterotoxic effects of all main oxysterols of non-enzymatic origin so far identified in a variety of foods. Experimental plan: differentiated human intestinal cell monolayers (CaCo-2) were incubated up to 48 h in the presence or absence of 0.5, 1 or 5 µM with one out of seven non-enzymatic oxysterols, prior verification of a minimal irreversible cell damage within the chosen concentration range. Results: all tested oxysterols were in vitro proven to exert damaging effects on cell monolayers. The inflammatory interleukin-8 and monocyte chemotactic protein-1 were mostly up-regulated by 7-ketocholesterol and 7β-hydroxycholesterol, respectively, then to a lower extent by 5α,6α-epoxycholesterol, 7α-hydroxycholesterol and 5β,6β-epoxycholesterol. 7-Ketocholesterol and 7β-hydroxycholesterol also appeared to be the most effective in impairing claudin-1, occludin and E-cadherin proteins, followed by 25-hydroxycholesterol and triol. Conclusions: the oxysterols consistently deriving by food autoxidation were tested: they potentially impaired the intestinal epithelial barrier integrity and triggered an inflammatory response already within the 0.5-5 µM concentrations easily reachable in a single Western meal. Significance: this comprehensive analysis focused on the potential impairment of intestinal barrier by the main dietary non-enzymatic oxysterols, should guide further nutrition research aiming at defining a threshold amount of these cholesterol derivatives in order not to derange the physiological gut-brain axis.
