Multi-omics atlas of the bovine coronavirus-infected calf jejunum: reduction of Phocaeicola coprophilus and deoxycholic acid linked to Th17/Treg imbalance.

Optimal calf rearing is fundamental for ensuring efficient milk production. Bovine coronavirus (BCoV) poses a significant threat to calf health and leads to substantial economic losses in the dairy industry. However, the mechanisms by which the intestinal mucosal microbiome regulates the host immune response during infection remain unclear. In this study, we constructed a high-resolution map of the jejunal mucosal microenvironment in BCoV-infected calves. Our findings revealed that BCoV infection led to severe microbial dysbiosis, characterized by a marked reduction in Phocaeicola coprophilus (formerly known as Bacteroides coprophilus) and decreased secondary bile acid, especially deoxycholic acid (DCA). Concurrently, enrichment of harmful microbiota correlated with increased arachidonic acid metabolites. At the host level, BCoV infection altered the composition of jejunal mucosal cells and affected metabolic and immune-related pathways. The differentiation of CD4⁺ T cells played a central role in the jejunum's response to BCoV infection. By integrating these metabolic alterations with dynamic host cellular responses, we suggested a putative that DCA deficiency might contribute to the pathological polarization of CD4+ T cells toward a Th17 phenotype while suppressing Treg differentiation. These findings suggest that restoring the Phocaeicola coprophilus-affected bile acid transformation might represent a promising therapeutic strategy for BCoV infection.