Modulating Immune Responses After Consistent Lipid Exposure

Background of the study: Enhanced immune responses can lead to chronic hyperinflammation, which contributes to the development of non-communicable diseases such as type 2 diabetes and cardiovascular disease. Poor dietary habits, particularly the consumption of high-fat meals, are thought to trigger this process by increasing the concentration of triglyceride-rich lipoproteins in the bloodstream, resulting in postprandial triglyceridemia. This state stimulates immune cell activation, elevates circulating lipopolysaccharide levels, and enhances the production of inflammatory mediators including IL-6, TNFα, VCAM1, and ICAM1, as well as changes in inflammatory gene expression in peripheral blood mononuclear cells. Until now, most research investigating the relationship between fat intake and postprandial inflammation has focused on the effects of a single high-fat meal. However, in daily life, individuals typically spend the majority of the day-up to 18 hours-in a postprandial state, continuously exposed to multiple meals containing a mix of macronutrients and fats from diverse sources. It remains unclear how repeated fat intake influences the timing, magnitude, and overall pattern of the postprandial immune response. The MIRACLE study is designed to address this gap by exploring how repetitive postprandial fat exposure affects circulating immune cells in healthy individuals, comparing the effects of plant-derived and dairy-derived lipids. The study employs a double-blind, randomized, cross-over, two-armed intervention design in which each participant acts as their own control. Objective of the study: The primary objective of the MIRACLE study is to determine how daily repetitive exposure to lipids from the same source modulates the postprandial immune response, as reflected by IL-6 levels, compared with acute exposure. Postprandial IL-6 concentrations will be measured using multiplex ELISA assays at multiple time points following the high-fat shake at baseline (T0) and after repeated exposure (T1). These data will allow calculation of protein dynamics and incremental area under the curve (iAUC) values for IL-6. Secondary objectives: Secondary objectives include comparing postprandial IL-6 iAUC values across T0, T1, and T2; comparing IL-6 responses between the plant- and dairy-derived fats; and identifying mechanisms underlying lipid-induced immunomodulation in PBMCs, including changes in immune cell functioning, phenotypes, and circulating inflammatory parameters. The study will also assess the effects of repeated fat intake on postprandial metabolic markers such as glucose and triglyceride levels. Glucose will be continuously monitored using glucose sensors, while other metabolic parameters will be measured in plasma. Additionally, the relationship between body composition, as assessed by Dual Energy X-ray Absorptiometry (DXA), and postprandial immune and metabolic responses will be evaluated at T0, T1, and T2. Study design: On each test day, a catheter cannula will be inserted into an antecubital vein, followed by a 30-minute rest period before measurements begin. Baseline blood samples (t = 0) will be drawn from the catheter, after which participants consume a 0.6 L high-fat shake containing 95 grams of fat from one of the two lipid sources. Subsequent blood samples will be collected at 0.5, 1, 2, 3, 4, and 6 hours post-consumption to monitor postprandial responses. Following the first test day, participants will consume smaller breakfast shakes (\~300 mL, \~20 grams of fat) daily for four consecutive weeks, using lipid powders corresponding to the same fat source. After these four weeks, the postprandial test day will be repeated following the same procedures as on the first day. After the second test day, a washout period of two weeks will take place before participants return for a third test day, again following the same protocol. This will be followed by another washout period of two weeks to three months before beginning the second arm of the study, during which participants will consume lipids from the alternate fat source. Thus, each participant completes both the plant-derived and dairy-derived fat interventions in a randomized order, ensuring within-subject comparison. Study population: 39 healthy male or female volunteers, age 40-70, BMI 22-27. Intervention: 2 different breakfast shakes based on either plant-derived or dairy-derived fat.