| Summary: | Currently, information available on the comprehensive changes in the rumen bacteria and metabolites of yaks fed high-grain diets is limited. This study aimed to investigate the effects of high-grain diet feeding on the blood metabolites, rumen microbiome, and metabolomics of yaks by using 16S rDNA gene sequencing and liquid chromatography–mass spectrometry (LC/MS). Here, fourteen healthy male yaks (body weight, 249.61 ± 8.13 kg) were randomly assigned to two different diets: a hay diet (0% grain, CON, <i>n</i> = 7), or a high-grain diet (70% grain, HG, <i>n</i> = 7). At the 74th day of treatment, blood and ruminal fluid samples were collected for the blood metabolites, rumen microbiome, and metabolomics analyses. The HG diet increased lipopolysaccharides (LPS), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), haptoglobin (HPT), serum amyloid-A (SAA), interleukin-1β (IL1-β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) serum concentrations (<i>p</i> < 0.05). Compared with the CON diet, the HG diet decreased rumen pH (<i>p</i> < 0.05), and increased total volatile fatty acids concentration, and proportion of butyrate (<i>p</i> < 0.05). The relative abundance of Firmicutes and Saccharibacteria were higher (<i>p</i> < 0.05), while Bacteroidetes was lower (<i>p</i> < 0.05) in the HG group than those in the CON group. At the genus level, the relative abundance of <i>Christensenelaceae_R-7_group</i>, <i>Ruminococcaceae_NK4A214_group</i>, <i>Lachnospiraceae_NK3A20_group</i>, and <i>Acetitomaculum</i> were higher than in those in the HG diet (<i>p</i> < 0.05). Compared with the CON group, the HG diet increased the concentrations of biogenic amines (histamine, tyramine, and putrescine), common amino acids (phenylalanine, threonine, serine, etc.), and arachidonic acid (prostaglandin H2, prostaglandin E2, 12(S)-HPETE, etc.). Collectively, these findings demonstrate that the HG diet altered the microbiota and metabolites, as well as potentially damaged their rumen health and induced inflammation in yaks.
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