Combined chlorogenic acid and baicalin supplementation alleviates PRRSV-induced disease by modulating immune responses and gut microbiota in weaned piglets.

UNLABELLED: Porcine reproductive and respiratory syndrome continues to pose a major challenge to the global swine industry, leading to substantial economic losses, and complicating disease management. This study evaluated whether dietary supplementation with chlorogenic acid and baicalin could alleviate clinical disease, modulate inflammatory and antiviral immune responses, and reshape the gut microbiota in porcine reproductive and respiratory syndrome virus (PRRSV)-infected weaned piglets. Forty-eight weaned male piglets were randomly assigned to four groups: negative control, PRRSV-infected positive control, low-dose treatment, and high-dose treatment. Piglets in the PC, LG, and HG groups were challenged with PRRSV, whereas the NC group received sterile PBS. During the experiment, the clinical manifestations of the piglets were recorded in detail. At 21 dpi, samples were collected to evaluate immune responses and gut microbiota composition. Compared with the PC group, the HG group showed only a mild and transient increase in rectal temperature, peaking at 3 dpi and returning to the normal range by 6 dpi, increased body weight by 21.0% at 21 dpi, reduced serum PRRSV RNA by 1.18 log10 copies/mL at 7 dpi, and decreased serum viral RNA to below the qPCR detection limit by 21 dpi. HG treatment also decreased TNF-α, IL-1β, and IL-6 by 26.1-40.9% and increased IFN-γ and IL-2 by 17.8-151.1% at day 21 dpi with PC. Microbiota analysis showed increased Lactobacillaceae abundance and reduced opportunistic taxa, including Clostridiaceae, Peptostreptococcaceae, and Staphylococcaceae. These findings suggest that combined chlorogenic acid and baicalin supplementation may serve as a promising adjunctive nutritional strategy for mitigating PRRSV-associated disease in weaned piglets. Further studies using contemporary field strains and long-term production trials are needed to validate its practical efficacy and safety. IMPORTANCE: Porcine reproductive and respiratory syndrome virus (PRRSV) causes severe economic losses in pig production and remains difficult to control because of viral variability and incomplete vaccine protection. This study shows that a chlorogenic acid-baicalin combination can reduce PRRSV-induced clinical disease, promote viral clearance, regulate inflammatory and antiviral immune responses, protect organs, and restore gut microbiota in infected piglets. These findings highlight the potential of plant-derived bioactive compounds as sustainable, antibiotic-free interventions for PRRSV control. The work provides experimental evidence supporting the development of natural functional feed additives to improve animal health and reduce reliance on conventional antimicrobial strategies in modern swine production.