title: Proteomic characteristics of plasma from calves with diarrhea before and after drug intervention
design: Dampness heat diarrhea (DHD) is the most common type of diarrhea in calves according to the Traditional Chinese veterinary medicine (TCVM) and its complex etiology bring great challenges to the treatment of this disease. Huangbai jianpi decoction (HBJP) is efficacy to treat DHD in calves. The therapeutic mechanism of HBJP is urgently required to be applied this decoction to the precise treatment of this syndrome in the clinic. We herein aimed to explore the mechanism of HBJP in DHD by using multi-omic analysis from DHD calves in Northwest China region. Proteomic results showed that some protein, including coagulation factor XIII B chain precursor (F13 B), alpha-1-acid glycoprotein precursor (ORM1) and polymeric immunoglobulin receptor (PIGR), had significant changes after treatment with HBJP. Metabolomics data demonstrated that the plasma of DHD calves were associated with high abundance of choline and pirbuterol, while after treated by HBJP the plasma was abundant in glycocholic acid and taurocholic acid. Bacterial gene sequence analysis showed that the feces of DHD calves had the highest abundance of Escherichia-Shigella, while after treated by HBJP the feces were more enriched in Megasphaera, Prevotella_2 and Bifidobacterium. Our study demonstrated that plasma proteins and metabolites, and gut microbiota were significantly different between before and after treated by HBJP in calves, and provided the theoretical basis for elucidating the mechanism of HBJP in the treatment of DHD.