To investigate the alleviating effects of Sparassis latifolia polysaccharide on the nephrotoxicity in lead(Pb)exposed mice and analyze the transmissibility of the alleviating effects under the co-housing mode,seventy-five Kunming mice were randomly divided into 5 groups,they were blank control group(NC group),Pb exposed group(Pb group),Sparassis latifolia polysaccharide group(SLP group),co-housing Pb exposed group(Co-Pb group)and the co-housing Sparassis latifolia polysaccharide group(Co-SLP group)(mice in the Co-Pb group and the Co-SLP group were put into the same cage),with 15 mice in each group.Drinking water of mice contained 1 g/L Pb2+except NC group.In addition to this,mice in the SLP and Co-SLP groups were intragastric with Sparassis latifolia polysaccharide,and mice in the NC,Pb and Co-Pb groups were given the same volume of saline,once a day.After 8 weeks of feeding,the lipid metabolism related indicators in the plasma and kidney were detected by a fully automated biochemical analyzer;the Pb content in the blood and kidney was measured by a graphite furnace atomic absorption spectroscopy;the renal tissue structure was ob-served using optical microscope;the oxidative stress related indicators including the activities of total superox-ide dismutase(T-SOD),glutathione peroxidase(GSH-Px)and catalase(CAT),and the glutathione(GSH)and malondialdehyde(MDA)contents in the kidney were determined by enzyme-linked immunosorbent assay(ELISA)kits;the mRNA relative expression levels of the inflammatory factor genes[interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),transforming growth factor-β(TGF-β),interleu-kin-4(IL-4)and interleukin-10(IL-10)]and autophagy genes[Beclin1,microtubule-associated protein light chain 3-Ⅰ(LC3-Ⅰ),microtubule-associated protein light chain 3-Ⅱ(LC3-Ⅱ),autophagy related gene 5(Atg5),ubiquitin binding protein p62(p62)and lysosomal associated membrane protein 2(Lamp2)]were detected using real-time fluorescence quantitative PCR;the relative abundance of intestinal flora at phylum level was analyzed by gene sequencing.The results showed that compared with the NC group,Pb exposure signifi-cantly increased the total cholesterol(TC),triglyceride(TG)and free fatty acids(FFA)contents in the plas-ma,the TG and TC contents in the kidney,and the Pb content in the blood and kidney(P<0.05);Pb expo-sure significantly decreased the activities of T-SOD,GSH-Px,CAT and GSH content(P<0.05),but signifi-cantly increased the MDA content(P<0.05);the pathological changes and deposition of lipid droplets in the renal tissues were observed in Pb group;Pb exposure significantly elevated the mRNA relative expression levels of inflammatory factor genes,such as IL-6,IL-1β and TNF-α,and the autophagy genes including Beclinl,LC3-Ⅰ,LC3-Ⅱ,Atg5,p62 and Lamp2(P<0.05),while significantly decreased the mRNA relative expres-sion levels of inflammatory factor genes including TGF-β,IL-4 and IL-10(P<0.05);Pb exposure significant-ly increased the relative abundance of Firmicutes in intestinal microbiota(P<0.05),while significantly de-creased the relative abundance of Bacteroides(P<0.05).Compared with the Pb group,the TG,TG and FFA contents in the plasma,the TG and TC contents in the kidney,and the Pb content in the blood and kidney in the SLP and Co-SLP groups were significantly decreased(P<0.05);the activities of T-SOD,GSH-Px,CAT and GSH content in the SLP and Co-SLP groups were significantly decreased(P<0.05),and the MDA con-tent was significantly decreased(P<0.05);the glomerular atrophy and lipid droplet deposition in the renal tis-sues were obviously alleviated in the SLP and Co-SLP groups;the mRNA relative expression levels of the in-flammatory factor genes IL-6 and IL-1β and the autophagy genes Beclin1,LC3-Ⅰ,LC3-Ⅱ,Atg5,p62 and Lamp2 in the kidney were significantly decreased(P<0.05),while the mRNA relative expression levels of TGF-β,IL-4 and IL-10 in the kidney were significantly increased in the SLP and Co-SLP groups(P<0.05);the relative abundance of Firmicutes in intestinal microbiota was significantly decreased(P<0.05),while the relative abundance of Bacteroides in intestinal microbiota was significantly increased in the SLP and Co-SLP groups(P<0.05).Compared with the Pb group,the Co-Pb group showed a significant decrease in the plasma TC and TG contents,and the Pb content in the blood and kidney(P<0.05);the activities of T-SOD,CAT and GSH content in the kidney were significantly elevated in the Co-Pb group(P<0.05);treatment with co-housing and Pb exposure significantly alleviated the glomerular atrophy and lipid droplet deposition in the renal tissue;the mRNA relative expression levels of the inflammatory factor genes TGF-β,IL-4,IL-10 and the auto-phagy genes Beclin1 and p62 were significantly reduced in the Co-Pb group(P<0.05);the relative abundance of Firmicutes in intestinal microbiota was significantly decreased in the Co-Pb group(P<0.05).All above indi-cate that the Sparassis latifolia polysaccharide can alleviate the renal damage caused by Pb exposure by reducing the Pb content in the blood and kidney,regulating the lipid metabolism,alleviating the oxidative stress,modu-lating the inflammatory reaction and inhibiting the autophagy injury,and it can transmit this protective effect through co-housing.[Chinese Journal of Animal Nutrition,2023,35(12):8097-8110]