Auricularia auricula polysaccharide alleviates cyclophosphamide-induced liver injury in mice involving remodeling of the gut bacteriome, mycobiome, and metabolome

In this study, a novel polysaccharide (AHP) from Auricularia auricula was isolated and purified, showing protective effects against CTX-induced liver injury in mice. To study the action mechanism of AHP, a liver injury model was established by intraperitoneally injection 80 mg/kg of CTX for 3 consecutive days. The focus was on how AHP regulated the gut bacteriome and mycobiome to help alleviate metabolic disorders associated with liver injury. Results showed that AHP amended liver injury by improving liver function, stabilizing oxidative stress homeostasis, reducing inflammatory invasion and activating Akt/GSK3β/Nrf-2/HO-1 signaling pathway. The 16S ribosomal DNA (16S rDNA) and Internal Transcribed Spacer-1 (ITS1) sequencing results demonstrated that AHP supplementation significantly restored the gut bacteriome and mycobiome composition in CTX-induced liver injury mice, by enriching the abundance of beneficial bacteriome (unclassified_Muribaculaceae, Faecalibaculum and Alloprevotella) and mycobiome (Fusarium), reducing the abundance of harmful bacteriome (Akkermanisa) and mycobiome (Fusicolla and Cladosporium). Analysis of untargeted metabolomics indicated that AHP altered the levels of metabolites associated with both bile acid and arachidonic acid metabolism, showing a significant connection to the AHP-regulated bacteriome and mycobiome. To conclude, the findings suggested that AHP was a viable and secure candidate for use as a hepatoprotective medication. [Display omitted] •A. auricula polysaccharide (AHP) is an α-pyranose with a molecular weight of 269.57 kDa.•AHP can reduce the symptoms of CTX-induced liver injury in mice.•Multi-omics revealed the hepatoprotective mechanism of AHP.