From digestion to inflammatory signaling: the Postprandial Bioactive Exposure Axis as a compartment-based conceptual model for mechanistic nutrition research

Mechanistic nutrition research often moves from what a meal contains to what it is claimed to do without clearly defining the exposure steps between ingestion and biological response. This becomes problematic when studies use causal or quasi-causal language about inflammation, barrier function or systemic effects. Digestion, intestinal interaction, epithelial uptake, enterocyte metabolism, microbial conversion, portal or lymphatic transport and post-absorptive handling can each alter the chemical form, concentration, timing and site of action of food-derived molecules. This article proposes the Postprandial Bioactive Exposure Axis, or PBEA, as a compartment-based model for organizing these steps in mechanistic nutrition research. The model separates four operational fractions: bioaccessible, intestinally bioactive, absorbed and systemically relevant. These fractions are levels of exposure inference, not discrete biological compartments. The aim is to help authors match claims to the compartment actually measured. The PBEA adds value by separating luminal availability from local intestinal action, and absorption from systemic relevance. It also helps prevent common overinterpretations, including equating intake with exposure, micellarisation with bioavailability, plasma detection with physiological relevance and indirect blood markers with direct evidence of altered barrier function. The model is intended as a practical tool for study design, model selection, temporal interpretation and more cautious mechanistic claims.