Abstract: In order to investigate the effect of long-term consumption of yak milk on the intestinal flora and metabolism and to explore the correlation between acclimation to monodiet and yak milk intake in high-altitude pastoral areas, this study used metagenomics and metabolomics to evaluate the gut microbial community structure and metabolites of mice fed yak milk or Holstein cow milk. Results showed that compared with the control group (normal saline solution), at the phylum level, ingestion of yak milk improved the relative abundance of Actinobacteria (33.27%), Bacteroidetes (24.31%) and Verrucomicrobia (11.08%), while ingestion of Holstein cow milk increased the relative abundance of Firmicutes (43.74%) and Bacteroidetes (24.75%). At the genus level, yak milk consumption increased the relative abundance of Ackermania (11.80%), Bacteroides (6.09%) and Limosilactobacillus (4.77%), while Holstein cow milk consumption increased the relative abundance of Lactobacillus (28.62%), Duncaniella (6.15%) and Limosilactobacillus (6.49%). Both yak and Holstein cow milk up-regulated carbohydrate and nucleotide metabolism. Furthermore, yak milk significantly up-regulated amino acid metabolism, cofactor and vitamin metabolism, energy metabolism, the biosynthesis of secondary metabolites, and the biosynthesis and metabolism of peptidoglycan. Metabolomics revealed that yak milk increased the contents of metabolites such as VB1, (+/-) 12 (13)-DiHOME, coenzyme Q2 and sulfonymethazine, as well as steroid hormone biosynthesis, cofactor biosynthesis, 2-oxyarboxylate metabolism, VB6 metabolism and phenylalanine metabolism in mice. Investigation of intestinal tissue morphology showed that the intestinal wall became thicker with increasing diversity and richness of the gut microbiota and the intestinal villi became longer and denser without deformity or breakage. In conclusion, yak milk has a positive effect on the intestinal flora and metabolism in mice, and this study provides a scientific basis for further development and utilization of yak milk.

Key words: yak milk; Holstein cow milk; intestinal flora; metabolism; intestinal morphology