Health Effects of Dietary Oxidized Milk Administration in Offspring Mice during Pregnancy and Lactation with Metabolomic Strategies

Milk is an important source of nutrients during pregnancy. Previous studies have consistently shown that oxidation in milk and dairy products can induce oxidative stress, inflammation, and fibrosis in the liver and kidney. However, the mechanism underlying these effects remains largely unexplored. This study aimed to investigate the effects of oxidized milk on fecal metabolism and liver and kidney function of offspring mice. Oxidative modification of milk was performed using H2O2-Cu or heating, causing varying degrees of oxidative damage. Kunming female mice were fed with a H2O2-Cu, heat, or normal control diet until their offspring were 3 weeks old. Feces were collected for the metabolomics study based on mass spectrometry. Forty-two potentially significant metabolic biomarkers were screened, and each group's relative intensity was compared. The results showed that oxidized milk mainly regulated isoleucine metabolism, proline metabolism, and tricarboxylic acid cycle. In addition, the histopathological analysis showed accumulation of protein and lipid oxidation products in the liver and kidney tissues after intake of oxidized milk, which induced oxidative stress, increased the levels of inflammatory factors, and significantly increased the expression of genes and proteins involved in inflammatory pathways. The above results suggest that intake of oxidized milk during gestation may increase the risk of liver and kidney injury in male offspring by interfering with amino acid and energy metabolism, highlighting the potential health risks of oxidized milk in humans.