Dietary silymarin improves gut-liver health by enhancing intestinal barrier integrity and modulating TLR4/NF-κB and NLRP3-mediated inflammatory responses in Aeromonas hydrophila-infected grass carp.

Bacterial infections compromise fish physiological homeostasis by impairing barrier function and metabolic organs, posing a persistent challenge in intensive aquaculture. Silymarin (SLM) is a plant-derived flavonoid complex obtained from Silybum marianum, widely recognized for its multifunctional pharmacological and bioactivity. However, its regulatory role under stress induced by bacterial pathogens in aquatic animals remains poorly understood. This study explored the impact and potential mechanisms of dietary SLM on intestinal barrier function and liver protection in juvenile grass carp. Fish (24.2 ± 0.1 g) were randomly assigned to six groups and fed diets containing 0, 20, 40, 60, 80, or 100 mg/kg SLM for 70 days. Subsequently, the fish were challenged with Aeromonas hydrophila (A. hydrophila) for 6 days. Optimal SLM supplementation (1) alleviated intestinal damage by upregulating tight junction proteins and downregulating myosin light chain kinase (MLCK); (2) reduced liver pro-inflammatory cytokines, inhibited lipopolysaccharide (LPS) translocation, and suppressed activation of the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway; (3) mitigated liver inflammation by inhibiting the phosphorylation of key nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathway proteins and downregulating nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome components; (4) decreased liver oxidative stress while enhancing antioxidant capacity and improving liver function; and (5) modulated gene expression related to metabolic enzymes and transporters in the intestine and liver. Dietary SLM improved gut-liver health by supporting barrier function, reducing inflammation, and enhancing metabolic and antioxidant responses, indicating its promise for nutritional use in aquaculture.