Multi-omics analysis of gut-liver axis reveals the mechanism by which sulforaphane alleviates liver injury in Cyprinus carpio exposed to triphenyltin

Abstract

This study investigates the protective effects of sulforaphane (SFN) against triphenyltin (TPT)-induced hepatotoxicity, immune dysfunction and gut microbiota dysbiosis in Cyprinus carpio. Cyprinus carpio were divided into three groups and exposed for 8 weeks, including control, 10 μg/L TPT and 10 μg/L TPT + 10 mg/kg SFN group. This result showed that TPT exposure induced significantly (P < 0.05) hepatotoxicity, evidenced by increasing hepatic total bile acid (TBA) and total cholesterol levels, while upregulating Hsp70/90 and downregulating lysozyme gene expression. SFN supplementation reduced TBA accumulation, normalized Hsp90 and lysozyme expression, mitigating TPT-induced lipid dysregulation and immunosuppression. Transcriptomic analysis revealed that TPT exposure activated lipid metabolism pathways (PPAR signaling and cholesterol metabolism), but suppressed immune-related pathways. SFN supplementation restored metabolic homeostasis by enriching glucose and amino acid metabolism pathways and activating AMPK signaling, while also modulating the expression of key genes (PLIN1, ME1, CPT1B). The microbiota composition were changed in SFN + TPT, including the increased of beneficial Fusobacteriota and Cetobacterium, and the decreased of pathogenic Proteobacteria and Aeromonas. The gut transcriptome dysregulation were restored in SFN + TPT by enhancing immune pathways in Toll-like/NOD-like receptors. The significant correlations linked were found in gut microbes (Kaistia, Vagococcus) to hepatic/intestinal gene expression in SFN + TPT. Overall, these findings elucidate novel mechanisms underlying TPT-induced immunotoxicity in liver and intestine and demonstrate the protective role of SFN, providing a theoretical foundation for its application in toxicity mitigation strategies.