Ruminal microbiota-derived inosine alleviates metabolic disorders in dairy cows supplemented with grape seed extract

Ruminal microbiota and their metabolites can shape host metabolic responses. Grape seed extract (GSE) can modulate ruminal microbiota profiles and metabolites in vitro, thus, underscoring their potential benefits on energy metabolism in dairy cows. In this study, Chinese Holstein cows were randomly divided into two groups (n = 10 per group) with or without dietary supplementation of GSE (15 g/d per cow) from -3 to 3 wk relative to calving. The results showed that GSE supplementation led to increased fat corrected milk yield (P = 0.003), feed efficiency (P = 0.045) and reduced milk somatic cell count (P = 0.031). In addition, GSE resulted in greater overall serum glucose (P = 0.011) and lower non-esterified fatty acids (P < 0.001), β-hydroxybutyric acid (P = 0.002), haptoglobin (P = 0.003), and serum amyloid A (P = 0.008) concentrations along with lower alanine/aspartate aminotransferase activity (P < 0.05). Compared with the control group, GSE supplementation altered the composition and metabolic profiles of ruminal microbiota (P < 0.05), with microbiota-derived inosine being greater both in serum (P < 0.001) and rumen fluid (P < 0.001). In addition, ruminal inosine correlated positively with milk production and alleviation of negative energy balance (r > 0.5, P < 0.05). Furthermore, just as GSE in vivo, exogenous inosine treatment elicited similar effects on energy metabolism and inflammation both in vitro (1 μmol/L, hepatocytes and adipocytes) and in dairy cows with ketosis (8 mg/kg per day, n = 5) (P < 0.05). Overall, results underscore a beneficial effect of ruminal microbiota-derived inosine in maintaining metabolic homeostasis postcalving. Thus, dietary GSE supplementation may improve energy metabolism and inflammatory state in dairy cows by enhancing ruminal-derived inosine production. Feeding GSE and inosine can be a potential strategy to alleviate health problems and optimize productivity in dairy cows during the transition period.