Licorice extract modulates immunity, enhances beneficial microbiota, and alleviates lung pathology in PRRSV-positive pigs: optimizing the dose and administration route

Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is a major immunosuppressive pathogen involved in the porcine respiratory disease complex. Licorice extract (LE) has anti-inflammatory, immune-regulating, and growth-promoting effects. In this study, the use of LE as a novel feed additive in PRRSV-infected nursery pigs was evaluated, and the effects of dietary supplementation and drinking water were compared. A total of 264 weaned piglets were allocated into 8 groups: three dietary supplementation groups (low, medium, and high doses: BLL, BLM, and BLH), three drinking water supplementation groups (low, medium, and high doses: WLL, WLM, and WLH), a farm control group (Farm), and a negative control group (CON). Compared with the CON group, dietary LE supplementation in the BLL and BLM groups significantly increased the average daily gain (ADG) by 1.02-fold and 1.18-fold ( P < 0.001) and reduced the feed-to-gain ratio (F/G) by 3.58% and 5.35% ( P < 0.05), respectively, compared with their drinking water counterparts, with the effects in the BLM group being the most pronounced. Additionally, compared with CON, LE administration via either route alleviated coughing, with significant downregulated ( P < 0.001) of cough scores in the BLH, WLL, and WLH groups during weeks 3–4. Furthermore, compared with the CON group, the BLM group exhibited increased tracheal cilia integrity ( P < 0.1) and significantly decreased ( P < 0.05) lung injury scores. While LE did not alter PRRSV-specific antigen or antibody levels ( P =0.065), it significantly modulated immune responses by downregulating IL-1β and IL-6 ( P < 0.05), upregulating IL-10 ( P < 0.05), and increasing IgA, IgG, and IgM levels ( P < 0.05). Gut metagenomic analysis revealed that LE notably increased the abundance of multiple beneficial bacteria and reshaped the structure of the gut microbiota. Specifically, LE upregulated Anaeromassilibacillus sp. An172 and reversed the antibiotic-induced decrease in the abundance of Bacteroides bouchesdurhonensis and Bacteroides sp. OF04‑15BH. These findings demonstrate that dietary LE, at an optimal dose of 2.6 g/kg, is a promising feed additive for PRRSV-infected pigs, with benefits mediated through immune modulation and gut microbiota remodeling.