Sheep milk has gained increasing attention for its compositional similarity to human milk and its abundance of bioactive compounds with nutritional and therapeutic potential.

This study explores the potential of sheep milk (SM) as a therapeutic treatment for ulcerative colitis (UC) in mice, focusing on its dose-dependent effects.

To fully investigate the effects of heat treatment on proteins and lipids in sheep milk, lipidomics and Astral-DIA proteomics combined with parallel reaction monitoring methods were used to analyze the changes of lipids and proteins after heat treatment at 65 °C for 30 min and 95 °C for 15 s. A total of 79 and 381 differential lipids and proteins were identified respectively. Lipidomics results show that Triacylglycerol (16:1_17:1_16:2) was unique in raw milk, whereas diacylglycerol (20:1_22:1) was unique in 95 °C group. Choline metabolism in cancer was the core metabolic pathway linked with heat treatment. Additionally, the collagen alpha-3(VI) chain protein (COL6A3), folate receptor-like domain-containing protein (FOLR1), and serpin domain-containing protein (JEQ12_008015) gradually disappeared with increasing heating temperature. The differentially expressed proteins were mainly associated with metabolic pathways. These analysis provide scientific connotation for the production of high quality dairy products and the healthy development of the dairy industry.