Novel top-down high-resolution mass spectrometry-based metabolomics and lipidomics reveal molecular change mechanism in A2 milk after CSN2 gene mutation

Abstract

The effects of milk containing only native A2 beta casein (A2 milk) on amelioration of gut tolerance are widely studied by clinical in vivo trials. However, the molecular change mechanism after CSN2 gene mutation and other potential health benefits in A2 milk remain unknown. The glycerophospholipid metabolism, sphingolipid metabolism, glycerolipid metabolism, phosphatidylinositol signaling system and glycosylphosphatidylinositol (GPI)-anchor biosynthesis were considered as significant metabolic pathways intimately related with the mutation of CSN2 gene by integrating metabolomics and lipidomics and the corresponding molecular mechanism was summarized. The contents of lactose, triacylglycerol and most polar lipids significantly decreased after CSN2 gene mutation by utilizing UHPLC-Q-Orbitrap HRMS (LOQs, 0.0004–0.0215 μg/mL) combined with multivariate analysis, furthermore, the essential fatty acids α-linolenic acid (1015.22 to 543.14 μg/mL) and arachidonic acid were significantly down regulated although eicosapentaenoic acid was relatively upregulated, which provided a novel perspective to understand the nutritional value and health benefits of A2 milk.