Dietary glycyrrhizic acid improves growth performance and modulates upper respiratory microbiota in weaned piglets

BACKGROUND: Natural products with dual immunomodulatory and antimicrobial functions offer promising strategies to reduce antibiotic use in livestock. Glycyrrhizic acid (GA), the principal bioactive component of licorice, has demonstrated anti-inflammatory and antiviral properties, yet its translational potential in swine health remains underexplored. This study evaluated the efficacy of GA in weaned piglets under commercial nursery conditions as an antibiotic alternative. A total of 225 weaned piglets were assigned to five groups: negative control (CON, basal diet), farm routine (FA, conventional antibiotics), and three GA-supplemented groups (GLL, 0.65 g/kg; GLM, 1.3 g/kg; GLH, 2.6 g/kg). RESULTS: The result showed that dietary GA supplementation (2.6 g/kg) numerically improved growth performance and reduced cough scores, although not statistically significant. GA significantly decreased the diarrhea index and improved skin scores. GA also significantly increased serum IgG and IgM levels in piglets and showed a trend toward higher IgA levels. Furthermore, GA exhibited a trend toward lowering serum IL‑1β levels while upregulating IFN‑γ and IL‑10 levels. Regarding antioxidant parameters, GA significantly upregulated T‑SOD, GSH‑PX, and CAT activities and downregulated LDH activity. Metagenomic analysis revealed that high‑dose glycyrrhizic acid (GA) significantly increased the abundance of Alloprevotella, while decreasing the abundances of Moraxella pluranimalium and 11 other pathogenic species associated with respiratory diseases and lung injury, including Glaesserella parasuis, Mesomycoplasma hyorhinis, Mesomycoplasma hyopneumoniae, Streptococcus suis, among others, thereby reshaping the upper respiratory tract microbiota of pigs. CONCLUSIONS: Collectively, these findings support GA as a viable non-antibiotic strategy for improving immune function, antioxidant capacity, and respiratory health in weaned piglets.