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

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.