Untargeted metabolomics reveals stage-specific metabolic signatures in yak colostrum, transitional milk and mature milk.

Yak milk's stage-specific metabolic profiles remain largely uncharacterized. In this study, yak colostrum (YC) was found to contain higher levels of essential components (e.g., milk fat, lactose, lactoprotein and non-fat solids) than transitional (YT) and mature milk (YM). A comprehensive untargeted profiling was conducted using UHPLC-Q Exactive HF-X to investigate the metabolic signatures of YC, YT and YM. A total of 2005 metabolites were identified. Metabolites enriched in YC were implicated in promoting intestinal microbiota colonization and supporting neonatal immune defense and neurodevelopment. In contrast, YM exhibited a metabolomic profile associated with sustained energy metabolism and the maturation of adaptive immune responses. YT exhibited a hybrid profile containing select bioactives characteristic of both YC and YM stages. Metabolites in YC and YT showed dynamic changes associated with circadian rhythm regulation and cognitive function under high-altitude hypoxia. This study reveals lactation-stage dynamics and supports functional development of yak milk products.