A notable finding of this study was the PNS-induced decreasing trend in hepatic SCFAs, as well as increased SCFA production in the small intestine observed in DIO-induced NAFLD mice, which indicated that an indirect effect of PNS on NAFLD progression was associated with gut permeability improvement by increasing the expression of tight junction-associated proteins (ZO-1 and Claudin-1). This evidence concerns the gene CLDN1 and metabolic dysfunction-associated steatotic liver disease.