Alkaline mineral complex water protects piglets against viral infection by driving cholesterol consumption through the GPAT2/SULT2A1 axis

Our previous work revealed that the anti-diarrhea effects of alkaline mineral complex (AMC) water improve metabolism and protect the gut during weaning stress. However, whether AMC water can inhibit viral replication and treat viral diarrhea is unknown. The aim of this study was to explore the ability of AMC water to improve nutrient metabolism and protect against infection. In this study, porcine epidemic diarrhea virus (PEDV) or porcine deltacoronavirus (PDCoV) were used as RNA model viruses, and pseudorabies virus (PRV) or porcine circovirus (PCV) were used as DNA model viruses. Compared with those in the infected group, the virus content in the piglets fed AMC water was reduced, and the intestinal mucosal barrier was repaired. Transcriptome and metabolome results revealed that AMC water regulated lipid metabolism through GPAT2, DGKA, OAT3, FXR, LIPC and SULT2A1. Further studies showed that glycerol, cholesterol, and bilirubin levels increased after viral infection, and that AMC water inhibited cholesterol content and promoted bile acid synthesis. In a cellular model, AMC water reduced lipid droplet density by activating the glycerolipid and bile secretion pathways of the GPAT2/SULT2A1 axis. In addition, knockdown of DGKA and overexpression of SULT2A1 significantly affected the expression of the GPAT2/SULT2A1 axis, and the expression of viral proteins colocalized with lipid droplets was significantly decreased. Our findings suggest that AMC water promotes cholesterol metabolism by activating the GPAT2/SULT2A1 axis, inhibiting viral infection in piglets. This study provides theoretical support for the use of nutritional regulation to inhibit viral infection and provides a new method for antiviral therapy.