Accumulating evidence suggests that dysregulation of the intestinal flora potentially contributes to the occurrence and development of nonalcoholic fatty liver disease (NAFLD). Phyllanthus emblica (PE), an edible and medicinal natural resource, exerts excellent effects on ameliorating NAFLD, but the potential mechanism remains unclear. In the present study, a mouse NAFLD model was established by administering a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). The protective effects of the aqueous extract of PE (AEPE) on the gut microbiota and fecal metabolites in NAFLD mice were detected by performing 16S rRNA gene sequencing and untargeted metabolomics. The administration of middle- and high-dose AEPE decreased the levels of ALT, AST, LDL-C, TG, and Hyp and increased HDL-C levels in CDAHFD-fed mice. Hematoxylin–eosin (H&E), Oil Red O, and Masson’s trichrome staining indicated that AEPE treatment attenuated hepatic steatosis and fibrotic lesions. Moreover, the disordered intestinal microflora was remodeled by AEPE, including decreases in the abundance of Peptostreptococcaceae, Faecalibaculum, and Romboutsia. The untargeted metabolomics analysis showed that AEPE restored the disturbed glutathione metabolism, tryptophan metabolism, taurine and hypotaurine metabolism, and primary bile acid biosynthesis of the gut bacterial community in NAFLD mice, which strongly correlated with hepatic steatosis and fibrosis. Collectively, AEPE potentially ameliorates NAFLD induced by a CDAHFD through a mechanism associated with its modulatory effects on the gut microbiota and microbial metabolism.

Liver fibrosis is a pathological variation caused by almost all chronic liver injuries. As an edible and medicinal natural resource, Phyllanthus emblica (PE) has been reported to possess hepatoprotective, antioxidant, and anti-inflammatory activities and may have an ameliorating effect on hepatic fibrosis. To investigate the protective effect of the aqueous extract of PE (AEPE) against liver fibrosis and to uncover its related mechanisms, the chemical profile of AEPE was characterized by high performance liquid chromatography (HPLC) and sulfuric acid-phenol method. Ameliorative effects of different doses of AEPE were investigated in carbon-tetrachloride- (CCl₄-) induced liver fibrosis rats by analyzing biochemical markers, morphologic pathology, and related proteins expression in liver tissue. The results indicated that AEPE (1.8, 3.6g/kg) could significantly reduce levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), collagen IV (Col IV), type III precollagen (PCIII), hyaluronic acid (HA), laminin (LN), malondialdehyde (MDA), nitric oxide (NO), protein carbonyl (PC), tumor necrosis factor-α(TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and hydroxyproline (Hyp) and increase the levels of superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT). Hematoxylin-eosin (H&E), Sirius red, and Masson staining showed AEPE-treated improved fibrotic lesions and inflammatory cell infiltration. Meanwhile, AEPE treatment also significantly downregulates the expression of α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) in the liver tissue and serum, respectively. In conclusion, AEPE possesses curative efficacy against liver fibrosis through its antioxidant, anti-inflammatory, and antifibrotic effects.