Study on the Effects and Mechanisms of an Ulvan Derivative in NAFLD through Gut Microbiota Fermentation

Nonalcoholic fatty liver disease (NAFLD) is closely associated with gut microbiota dysbiosis and lacks effective therapies. This study evaluated the effects of HU, a high-sulfated derivative of Ulva pertusa polysaccharide, using an HFD-induced NAFLD mouse model. Structural characterization showed that HU possessed a porous and aggregated surface morphology with heterogeneous nanoscale features. In HFD-fed mice, HU significantly reduced body weight gain, hepatic lipid accumulation, and inflammation, while improving serum biochemical parameters, including 44.0% lower triglycerides and 30.7% lower aspartate aminotransferase levels.16S rRNA sequencing revealed that HU markedly modulated gut microbial composition. In vitro fermentation showed enrichment of beneficial genera, while in vivo experiments demonstrated increased Faecalibaculum and reduced Acinetobacter. Fecal microbiota transplantation further supported the involvement of HU-modulated gut microbiota in the protective effects against HFD-induced NAFLD. These findings suggest that HU ameliorates NAFLD by reshaping gut microbiota, suppressing inflammation, and alleviating hepatic lipid accumulation.