Metabolomic insights into thiamine-mediated metabolism in treating subclinical ketosis in dairy cows

代谢组学视角下的硫胺素介导代谢在奶牛亚临床酮病治疗中的作用

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Abstract

INTRODUCTION: Subclinical ketosis (SCK) is a common condition in dairy cows, primarily caused by the excessive accumulation of β-hydroxybutyrate (BHBA). Research has shown that succinyl-CoA is negatively correlated with the production of hepatic BHBA, while it is positively correlated with the utilization of BHBA in peripheral tissues. This correlation is significantly modulated by thiamine levels. Therefore, the purpose of this study is to investigate whether thiamine serves as a critical rate-limiting cofactor in succinyl-CoA metabolism, potentially enhancing BHBA utilization and reducing the incidence of SCK. METHODS: To verify the purpose of the study, 60 SCK dairy cows with comparable body weight, milk yield, and lactation days were selected from a total of 1,126 dairy cows reared in the same environment. The selection was based on the criterion of blood beta-hydroxybutyrate concentration being greater than 1.2 mmol/L. Another 12 healthy dairy cows with similar productive performances were enrolled in the control treatment. Milk yield, milk quality, rumen fermentable parameters, rumen and blood metabolomics were measured to investigate the alleviative effects of thiamine on SCK. RESULTS AND DISCUSSION: The results showed that thiamine significantly decreased plasma BHBA concentrations, milk colony-forming units (CFU), and somatic cell counts, while significantly increasing milk yield, milk fat content, acetate levels, and the acetate-to-propionate (A/P) ratio compared to SCK cows (p < 0.05). Metabolomic analysis revealed that the upregulated metabolites in both the rumen and blood after thiamine supplementation were significantly enriched in the pathways of pyruvate metabolism, glycolysis or gluconeogenesis, tyrosine metabolism, and glycerophospholipid metabolism, while the downregulated metabolites were mainly enriched in ascorbate and aldarate metabolism, glycerophospholipid metabolism, pentose and glucuronate interconversions, and riboflavin metabolism. Collectively, thiamine supplementation effectively alleviated subclinical ketosis by promoting the mediated catabolism of succinyl-CoA for BHBA utilization, improving ruminal fermentability, and thereby enhancing the milk yield and quality.

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