Abstract
Lead (Pb) contamination is a major threat to aquaculture and food safety, mainly due to its hepatotoxic and oxidative impacts on fish. This study evaluated the ameliorative role of yeast-derived prebiotics, mannan oligosaccharides (MOS) and β-glucan (βG), against Pb-induced toxicity in Nile tilapia (Oreochromis niloticus). A total of 180 fish were allocated into four treatment groups for eight weeks: control, MOS/βG-supplemented diet (0.3%), Pb exposure (10 mg/L), and combined Pb with MOS/βG supplementation. Pb exposure significantly reduced serum total protein, albumin, and globulin while increasing hepatic enzymes, indicating liver dysfunction. Severe hepatic necrosis, hepatopancreatic degeneration, gill lamellar fusion, and mitochondrial disruption were also observed, alongside elevated Pb residues in liver > gills > muscles. Dietary MOS/βG markedly restored altered biochemical markers, improved histoarchitectural and ultrastructural integrity, and reduced Pb accumulation in all tissues compared with Pb-exposed fish (p < 0.05). These findings demonstrate that MOS/βG supplementation enhances physiological resilience to heavy metal stress and is associated with reduced Pb bioaccumulation, highlighting their potential as a sustainable nutritional intervention to protect fish health and reduce tissue contamination in Pb-polluted aquaculture environments. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-37841-z.