MODULATION OF INTESTINAL BARRIER FUNCTION AND NUTRITIONAL STATUS USING A CHITOSAN–SKIM MILK POWDER COMPLEX: AN IN-SILICO FRAMEWORK AND MORPHOFUNCTIONAL CORRELATIONS

Abstract

The intestinal barrier is a key regulator of host homeostasis, balancing selective nutrient absorption with protection against endotoxins and inflammatory triggers. Chitosan is a cationic biopolymer with mucoadhesive and sorption properties and is widely considered a functional ingredient. However, depending on dose, molecular weight and protonation state, chitosan may bind micronutrients and alter lipid assimilation, potentially shifting the benefit–risk balance. Complexation of chitosan with a protein matrix, including skim milk powder (SMP) fractions, may provide controlled release, improved colloidal stability and a food-matrix effect that supports mucosal integrity [14–20]. This paper proposes an in silico framework and an experimentally testable design to evaluate the chitosan–SMP complex as a barrier- and nutrition-modulating system. The model assumes 60 male Wistar rats allocated into five groups and fed for 42 days with low-/high-molecular-weight chitosan, either alone or complexed with SMP. Barrier integrity is assessed using a multi-parameter panel: villus–crypt morphometry, ultrastructural evaluation, tight junction proteins (ZO-1, occludin, claudin-1), mucus marker MUC2, and functional absorption tests (D-xylose and paracellular permeability proxies). Based on mechanistic evidence, the SMP matrix is expected to mitigate excessive sorption-related drawbacks while enhancing epithelial recovery and stabilizing nutritional indices (absorption efficiency, antioxidant status, micronutrient balance). The framework may guide dose–molecular-weight–matrix optimization and supports future in vivo validation and translational applications in functional nutrition and enteral delivery systems.