The food matrix as a confounder in diet‒microbiome studies: methodological challenges and research gaps

Interactions of structural and physicochemical properties of food (e.g. texture, viscosity, and solubility), known as the food matrix, are primary drivers of host digestive kinetics. While the impact of matrix-driven variability on nutrient bioaccessibility, glycemic response, and caloric absorption is well documented, these dynamics are often overlooked in diet-microbiome research. Adequately modeling the spatiotemporal availability of microbial substrate is essential to understanding how dietary patterns impact the microbiome throughout the gastrointestinal tract. This narrative review 1) synthesizes current evidence on how food processing and structure affect human digestion and absorption of macronutrients; 2) illustrates how host digestive kinetics impact forms and quantity of substrate delivered and available to the gut microbiota; and 3) identifies challenges and knowledge gaps in current diet-microbiome research regarding food structure. The challenges and knowledge gaps discussed here call for in vivo models that can better model microbial substrate availability throughout the gastrointestinal tract to improve our understanding of diet-microbiome interactions.