Dietary Astragalus polysaccharide mitigates lead-induced oxidative stress, metabolic dysfunction, and intestinal microbiota dysbiosis in Litopenaeus vannamei

Lead (Pb) is a well-known toxic heavy metal that induces oxidative stress, tissue damage, and neurotoxicity in several aquatic species including Litopenaeus vannamei . Howerver, the effective mitigation strategies remain limited. Astragalus polysaccharide (APS) is recognized for its antioxidant and detoxifying properties. In this study, the mitigating role of dietary APS against chronic Pb-induced toxicity we investigated in the L. vannamei from the aspects of oxidative stress, metabolism dysfunction, and intestinal microbiota. Shrimp with an initial weight of 0.40 ± 0.01 g were reared for 56 days under four treatments: no Pb and no APS (CG), Pb exposure without APS (P0), Pb exposure with 0.2 g/kg APS (P0.2), and Pb exposure with 0.4 g/kg APS (P0.4). The results showed that Pb exposure caused hepatopancreatic damage and reduced survival, whereas dietary supplementation with 0.4 g/kg APS effectively alleviated hepatopancreatic injury and improved survival. Pb exposure significantly suppressed intestinal amylase and lipase activities, as well as hepatic acetylcholinesterase and glutathione S-transferase activities. Pb exposure also increased hepatic oxidative stress indicators, including catalase, superoxide dismutase, and glutathione peroxidase activities, and elevated reactive oxygen species and malondialdehyde levels. Notably, APS supplementation reversed these Pb-induced changes. Pb exposure significantly decreased the Shannon, Simpson, Chao, and ACE indices and reduced the relative abundance of beneficial bacteria (including Psychrobacter , Bacillus , and Demequina ), while increasing harmful taxa (including Vibrionaceae and Flavobacteriaceae, as well as Photobacterium and Vibrio ). These alterations were also reversed by APS supplementation. Metabolomic analysis indicated that Pb exposure increased intestinal γ-aminobutyric acid and acetylcholine levels and decreased D-erythro-imidazolylglycerol phosphate and phenylpyruvate levels, whereas these metabolites were normalized by dietary APS at 0.4 g/kg. In conclusion, dietary supplementation with 0.4 g/kg APS effectively alleviated Pb-induced oxidative stress, neurotoxicity, metabolic dysfunction, and intestinal dysbiosis in L. vannamei . • APS improves survival ratio and hepatopancreatic tissue damage of L.vannamei exposed to Pb. • APS promoted the repair of nerve damage and detoxification in Pb-exposed L. vannamei. • APS attenuated oxidative stress, abnormal activity of digestive enzymes in Pb-exposed L vannamei. • APS restored intestinal microbiota homeostasis in Pb-exposed L.vannamei through modulation of intestinal metabolites.