Rumen Mycobiome Thiamine Metabolism Contributes to Subacute Rumen Acidosis Tolerance in Goats Through Enhancing Epithelial Cell Proliferation via IGFBP2/IGF1 Axis Activation

Abstract

Subacute rumen acidosis (SARA) is a critical metabolic disorder in dairy ruminants that threatens their milk production. However, the mechanisms by which rumen fungi influence the susceptibility and tolerance of ruminants to SARA remain unclear. This study investigated the relationship between rumen fungal metabolic functions and host SARA tolerance by examining the rumen epithelial miRNA-mRNA correlations and further cell subtype variations affected by fungi. SARA-susceptible and SARA-tolerant goats were identified by monitoring the dynamic rumen pH during high-concentrate feeding. The abundance of anaerobic fungi and their cellulose and amino acid metabolic functions were reduced in SARA-susceptible goats, but the enrichment of Aspergillus bombycis, which is associated with increased thiamine metabolism, offers potential for SARA tolerance. Furthermore, this study revealed that Aspergillus bombycis negatively regulates the rumen epithelial chi-miR-17-26080 through enhanced thiamine metabolism, thereby reducing its inhibitory effect on insulin-like growth factor binding protein 2 (IGFBP2). The tolerance mechanism of SARA was further explored by adding thiamine to high concentrations, which revealed that the upregulation of IGFBP2 promoted rumen epithelial IGF1 recruitment and increased the content of IGF1, which activated the ERK and PI3K/AKT pathways, further increasing the expression of CDK4 and Cyclin A2 and promoting the rumen epithelial cells' proliferation. The increased number of rumen spinous and basal cells in SARA-tolerant goats enhances volatile fatty acids absorption in dairy goats, leading to improved SARA tolerance. These findings highlight the roles of rumen fungi and their produced thiamine in preventing SARA in ruminants by enhancing epithelial cell proliferation via the IGFBP2/IGF1 axis activation.

Keywords

miRNA / rumen mycobiome / single-nucleus transcriptome / subacute rumen acidosis

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