The　purpose　of　this　study　was　to　assess　the　potential　effects　of　polysaccharides　from　edible　mushroom　Grifola　frondosa　(GFP)　on　lipid　metabolic　disorders　and　gut　microbiota　dysbiosis,　and　elucidate　their　possible　regulatory　mechanisms　on　lipid　and　cholesterol　metabolism　in　high-fat　diet　(HFD)-exacerbated　hyperlipidemic　and　hypercholesterolemic　rats.　Results　showed　that　oral　administration　of　GFP　markedly　alleviated　dyslipidaemia　through　decreasing　the　serum　levels　of　total　triglycerides,　total　cholesterol,　and　free　fatty　acids,　and　significantly　suppressing　hepatic　lipid　accumulation　and　steatosis.　Besides,　the　excretion　of　fecal　bile　acids　was　also　promoted　by　oral　administration　of　GFP.　Metagenomic　analysis　revealed　that　GFP　supplementation　(400　mg　kg-1　day-1)　resulted　in　significant　structure　changes　on　gut　microbiota　in　HFD-fed　rats,　in　particular　modulating　the　relative　abundance　of　functionally　relevant　microbial　phylotypes　compared　with　the　HFD　group.　Key　microbial　phylotypes　responding　to　GFP　intervention　were　identified　to　strongly　correlate　with　the　lipid　metabolism　disorder　associated　parameters　using　the　correlation　network　based　on　Spearman＇s　correlation　coefficient.　Serum　and　hepatic　lipid　profiles　were　found　positively　correlated　with　Clostridium-XVIII,　Butyricicoccus　and　Turicibacter,　but　negatively　correlated　with　Helicobater,　Intestinimonas,　Barnesiella,　Parasutterella,　Ruminococcus　and　Flavonifracter.　Moreover,　GFP　treatment　(400　mg　kg-1　day-1)　regulated　the　mRNA　expression　levels　of　the　genes　responsible　for　hepatic　lipid　and　cholesterol　metabolism.　Oral　supplementation　of　GFP　markedly　increased　the　mRNA　expression　of　cholesterol　7α-hydroxylase　(CYP7A1)　and　bile　salt　export　pump　(BSEP),　suggesting　an　enhancement　of　bile　acid　(BA)　synthesis　and　excretion　from　the　liver.　These　findings　illustrated　that　GFP　could　ameliorate　lipid　metabolic　disorders　through　modulating　specific　gut　microbial　phylotypes　and　regulating　hepatic　lipid　and　cholesterol　metabolism　related　genes,　and　therefore　could　be　used　as　a　potential　functional　food　ingredient　for　the　prevention　or　treatment　of　hyperlipidemia.　©　2019　The　Royal　Society　of　Chemistry.