Effects of Tributyrin on Antioxidant Capacity, Immune Function, and Liver Macrophage Polarization in Weaned Piglets Under LPS Challenge

Under intensive farming systems and the global ban on antibiotic growth promoters (AGPs), early-weaned piglets exhibit incomplete physiological development, increasing their susceptibility to stress-related liver dysfunction and growth performance impairments. This study first investigated the effects of dietary supplementation with 0.2% tributyrin on the growth performance of 21-day-old weaned piglets over a 28-day period. Subsequently, on the final day, we examined its influence on antioxidant capacity, immune responses, and liver macrophage polarization using a 2 × 2 factorial challenge model, with the factors being diet (basal or tributyrin-supplemented) and immunological challenge (saline or lipopolysaccharide). The experimental results indicated that tributyrin had a significant enhancement on the average daily gain (ADG) of weaned piglets within the 0-14-day period (<i>p</i> < 0.05). Under lipopolysaccharide (LPS) challenge, tributyrin significantly increased the levels of catalase (CAT) and interleukin-10 (IL-10) while reducing the levels of malondialdehyde (MDA) and interleukin-6 (IL-6) in both serum and liver. Additionally, it significantly increased glutathione peroxidase (GSH-pX) activity in the serum and reduced glutathione (GSH) levels in the liver, and also decreased the serum level of interleukin-1β (IL-1β). Tributyrin downregulated pro-inflammatory cytokine gene expression while upregulating anti-inflammatory cytokine expression (<i>p</i> < 0.05). Furthermore, tributyrin significantly inhibited the expression of M1 macrophage polarization markers while enhancing those of M2 polarization (<i>p</i> < 0.05). Additionally, tributyrin suppressed SIRT1/NF-κB signaling pathway activation and promoted JAK2/STAT6 signaling pathway activation (<i>p</i> < 0.05). These findings exhibit that tributyrin alters the polarization of liver macrophages by regulating the SIRT1/NF-κB and JAK2/STAT6 signaling pathways, enhances antioxidant and immune functions, reduces LPS-induced liver inflammatory damage, and improves the growth performance of weaned piglets.