Characterising high-resolution dynamics of inflammatory and SCFA responses to food consumption in healthy men: A pilot biomarker discovery study

Understanding inflammatory responses after food consumption and at fasting is crucial for assessing the impact of diet on long-term health. To study these responses meaningfully, biomarkers must be responsive to food intake, consistent across individuals, and predictive of future health outcomes. Preliminary data suggest that anti-inflammatory short-chain fatty acids (SCFAs), produced by the microbiota from prebiotic fibre, might be relevant biomarkers in the food-induced inflammatory reaction, but data on their timing, magnitude, dynamics at fasting and during the postprandial state, and relationship with other biomarkers are currently lacking. This knowledge gap impacts our ability to identify reliable biomarkers that can be used as surrogate outcomes in dietary interventions and research focused on reducing chronic disease risk. In this biomarker discovery study, we aimed to identify meal-responsive inflammatory biomarkers and assess plasma SCFAs pharmacokinetics following meal intake. Three healthy male participants consumed three isoenergetic meals with different theoretical pro-inflammatory potential, one per week over a three-week period: an anti-inflammatory meal (Meal A), a pro-inflammatory meal (Meal B), and a pro-inflammatory meal with a butyrate-promoting prebiotic fibre supplement (Meal C). For each meal condition, blood samples were taken continually over a 30-h period, and inflammatory cytokines and plasma SCFAs were measured. Cytokine biomarker dynamics were classified based on their response to meals. We identified 26 meal-responsive biomarkers, with three-CST5, FGF-19, and ST1A1-showing consistent postprandial changes across participants. The study also revealed significant interindividual variability, with 23 biomarkers displaying highly personalised responses to food intake. Quantitative analysis of plasma SCFA concentrations indicated non-trivial dynamics, but a clear accumulation of butyrate, acetate, and propionate in plasma during a 25-h period following meal intake. Our findings highlight the complexity of the postprandial response, emphasising the need for thoughtful consideration of study design, including the choice and sampling rate of biomarkers. The identified biomarkers offer potential for future research and clinical applications, improving the understanding of diet-induced inflammation and its role in chronic disease prevention.