Identification of the molecular mechanisms underlying brisket disease in Holstein heifers via microbiota and metabolome analyses.

Brisket disease (BD) is common among Holstein heifers in high-altitude environments, and this disease may result in serious economic loss. At present, no effective treatment is available for brisket disease. In this study, liver and cecum samples were collected from five heifers with BD and five healthy heifers (HH) for analyses of the metabolome and microbiota. The mean pulmonary arterial pressure and systolic blood pressure were significantly higher in BD heifers, whereas the average breathing rate, blood oxygen saturation, and glucose level were significantly lower in BD group than in the HH group. Further, 16S rDNA data showed that the abundance of Firmicutes was significantly lower and that of Bacteroidetes was significantly higher in BD group than in the HH group. At the genus level, the BD group heifers harbored fewer Ruminococcaceae and Lachnospiraceae than the HH group. Several metabolites, including beta-D-fructose, D-ribose, 1,4-beta-D-glucan, sucrose, and glucose-6-phosphate were present at low levels in BD heifers. Moreover, the mean pulmonary arterial pressure was negatively correlated with beta-D-fructose (r =  - 0.74; P = 0.013), D-ribose (r =  - 0.72; P = 0.018), and acetyl-tyrosine-ethyl-ester (r =  - 0.71; P = 0.022). We also found that mean pulmonary arterial pressure was negatively correlated with most of the genera, including those in the families of Lachnospiraceae and Ruminococcaceae. In summary, the decreased levels of metabolites and microbial genera might affect BD by limiting the energy supply. This study may help us better understand the role of the microbiota in BD and provide new insights into the management of feeding to decrease the rate of BD in Holstein dairy cows in the Qinghai-Tibetan plateau.