An in vitro digestion model accounting for sex differences in gastro-intestinal functions and its application to study differential protein digestibility

Abstract

It is increasingly recognized that differences in gut functions govern the digestive fate of foods and oral formulations. Yet, sex-based differences are scantly addressed in food digestion research despite evidence of their implications to the performance of pharmaceutics. This work conducted a wide review and sieved 40 clinical trials to underpin sex-based differences in oral, gastric and intestinal parameters. Detailed information on identified gut function differences is detailed, for example sex-based differences in gastric pH, pepsin levels and gastric emptying as well as various intestinal parameters. In turn, quantitative parameters were applied to a computer-controlled set of bioreactors to generate an in vitro digestion model of healthy men or women. Subsequently, these models were applied to study the gastro-intestinal breakdown of lactoferrin (LF), β-lactoglobulin (β-lac), α-lactalbumin (α-lac) or whey protein concentrate (WPC) by SDS-PAGE and LC-MS/MS. This revealed specific protein regions localized to the outer rims of β-lac and α-lac were differentially degraded in men and women. Bioinformatic analysis of gastric effluents highlights possible differences in generation of bioactive peptides, such as the satiety-affecting peptides LIVTQTMKG (lacto-ghrestatin) and VAGTWY (DPP-IV inhibitor). Thus, this work details a new tool for in vitro digestion modeling which opens avenues for research towards tailoring healthier food solutions for healthy women which may be distinguishable from those offered to men. • Human trials were mined for sex-based differences in gastro-intestinal functions. • An in vitro digestion model recreating GI functions of women was developed. • Specific protein regions localized to the outer rims of whey proteins are differentially degraded. • Proteomic analyses illustrate differences in generation of bioactive peptides in men or women. • This work opens new avenues for engineering foods for women.