Potential Mechanisms of Improved Activity of Natural Killer Cells Induced by the Consumption of F-MRP for 8 weeks

Scope: The authors used metabolomics to investigate the nutritional modulatory effect of fermented Maillard-reactive whey protein (F-MRP) on the activity of natural killer (NK) cells. Methods and Results: Fifty subjects who had participated in our previous intervention study were included in the present study in the test (n = 20) and placebo groups (n = 30). Additional analyses using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) and gas chromatography (GC)-MS were conducted to identify relevant metabolic features. After 8 weeks, the activity of lipoprotein-associated phospholipase A₂ (Lp-PLA₂) (p = 0.021), levels of interleukin (IL)-1β (p = 0.001), and activity of NK cells were considerably increased in the test group compared with those in the placebo group. Based on the metabolites discovered by UPLC-MS, ten altered metabolic pathways were observed in the test group after 8 weeks of F-MRP consumption. Specific pathways with most pronounced associations with immune-enhancing effect of F-MRP included aminoacyl-tRNA biosynthesis, glycine/serine/threonine metabolism, arginine/proline metabolism, and sphingolipid metabolism. Conclusions: The present study demonstrated the effects of 8 weeks of F-MRP supplementation on the metabolic status manifested as changes in the Lp-PLA₂ activity, IL-1β level, and activity of NK cells. Intermediate metabolites of the identified metabolic pathways can be used to confirm the immune-enhancing efficacy of short-term supplementation.