Dietary Paeonol Supplementation Alleviates Waterborne Cadmium-Induced Damages in Gut Barrier Function in Largemouth Bass (Micropterus salmoides)

Waterborne cadmium (Cd) remains a significant threat to the intestinal health and growth of largemouth bass ( Micropterus salmoides ), necessitating the search for effective dietary mitigants. In this 56-day trial, the protective efficacy of paeonol (PAE) was evaluated across five experimental groups: a negative control, a Cd-stressed group (Cd, 2.75 mg/L waterborne exposure), and three treatment groups concurrently exposed to 2.75 mg/L Cd and supplemented with dietary PAE at 100, 200, and 400 mg/kg, respectively. The results showed that Cd exposure induced intestinal oxidative stress, impaired structural integrity, downregulated antimicrobial peptide expression, compromised immune function, and disrupted intestinal microbial homeostasis ( P  < 0.05). PAE supplementation significantly decreased malondialdehyde (MDA) content, and the PAE200-Cd exhibited increased activities of total superoxide dismutase (T-SOD) and catalase (CAT), as well as elevated expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and cytochrome P450 1A1 (CYP1A1) ( P  < 0.05). Intestinal villus structure was restored, the number of goblet cells increased, and the expression of tight junction proteins (Occludin, ZO-1, Claudin-1) genes was significantly upregulated ( P  < 0.05). Meanwhile, the expression of β-defensin, Lysozyme, and Mucin 2 was significantly upregulated ( P  < 0.05). The PAE100-Cd showed increased expression of immunoglobulins (e.g., IgM and IgT), while the PAE200-Cd inhibited the expression of pro-inflammatory factors ( P  < 0.05). Cd-induced negative changes in intestinal microbial diversity and stability were restored by PAE, and the PAE200-Cd exhibited decreased abundances of Proteobacteria and Pseudomonas , and increased abundance of Firmicutes ( P  < 0.05). Under the present experimental conditions, the appropriate dietary PAE level based on oxidative stress and intestinal physical barrier was preliminarily estimated to be 115.51–229.55 mg/kg. Collectively, PAE can alleviate Cd-induced intestinal injury by improving antioxidant capacity and enhancing intestinal barrier function, and represents a promising functional candidate for heavy metal mitigation. Graphical The alternative text for this image may have been generated using AI.