Bread crust constitutes an important by-product of the bakery industry, and its utilization
for the isolation of melanoidins to be used as a functional ingredient can enhance its added value
and contribute to health. The aim of this study was to evaluate the bioaccessibility, bioactivity, and
genoprotective effect of melanoidins derived from bread crust. Bioaccessibility was assessed in
gastric, intestinal digestion, and colonic fermentation fractions. The results revealed a relationship
between bioaccessible melanoidins and their type (common or soft bread). No cytotoxicity effects
were observed for bioaccessible fractions, as assessed by MTT and RTA methods, and they did not
affect the distribution of E-cadherin in Caco-2 cells, confirming their ability to maintain membrane
integrity. Furthermore, our study demonstrated that the gastrointestinal and colonic fermentation
fractions successfully transported across the intestinal barrier, without affecting cell permeability, and
showed antioxidant activity on the basolateral side of the cell monolayer. Remarkably, both fractions
displayed a significant genoprotective effect in Caco-2 cells. Our findings provide crucial insights
into the relationship between the melanoidins and their bioactivity and genoprotective effect. These
results demonstrated the potential of bioaccessible melanoidins as valuable bioactive compounds for
the development of functional foods, without showing toxic effects on gastrointestinal cells.
