Porphyran-derived oligosaccharides alleviate NAFLD and related cecal microbiota dysbiosis in mice.

Porphyran and its derivatives possess a variety of biological activities, such as ameliorations of oxidative stress, inflammation, hyperlipemia, and immune deficiencies. In this study, we evaluated the potential efficacy of porphyran-derived oligosaccharides from Porphyra yezoensis (PYOs) in alleviating nonalcoholic fatty liver disease (NAFLD) and preliminarily clarified the underlying mechanism. NAFLD was induced by a high-fat diet for six months in C57BL/6J mice, followed by treatment with PYOs (100 or 300 mg/kg/d) for another six weeks. We found that PYOs reduced hepatic oxidative stress in mice with NAFLD, which plays a critical role in the occurrence and development of NAFLD. In addition, PYOs could markedly decrease lipid accumulation in liver by activating the IRS-1/AKT/GSK-3β signaling pathway and the AMPK signaling pathway in mice with NAFLD. PYOs also apparently relieved the hepatic fibrosis induced by oxidative stress via downregulation of TGF-β and its related proteins, so that liver injury was markedly alleviated. Furthermore, PYOs treatment relieved cecal microbiota dysbiosis (such as increasing the relative abundance of Akkermansia, while decreasing the Helicobacter abundance), which could alleviate oxidative stress, inflammation, and lipid metabolism, and protect the liver to a certain degree. In summary, PYOs treatment remarkably improved NAFLD via a specific molecular mechanism and reshaped the cecal microbiota.