Abstract
Background and Aims Nonalcoholic fatty liver disease (NAFLD) is an alarming global health problem that is predicted to be the major cause of cirrhosis, hepatocellular carcinoma, and liver transplantation by next decade. Gut microbiota have been revealed playing an important role in the pathogenesis of NAFLD. Sheng-Jiang Powder (SJP), an empirical Chinese medicine formula to treat NAFLD, showed great hepatoprotective properties, but the impact on gut microbiota has never been identified. Therefore, we performed this study to investigate the effect of SJP on gut microbiota in NAFLD mice. Methods NAFLD was induced by 12 weeks' high-fat diet (HFD) feeding. Mice were treated with SJP/normal saline daily for 6 weeks. Blood samples were obtained for serum biochemical indices and inflammatory cytokines measurement. Liver tissues were obtained for pathological evaluation and oil red O staining. The expression of lipid metabolism-related genes was quantified by RT-PCR and Western blotting. Changes in gut microbiota composition were analyzed by the 16s rDNA sequencing technique. Results HFD feeding induced significant increase in bodyweight and serum levels of TG, TC, ALT, and AST. The pathological examination revealed obvious hepatic steatosis in HFD feeding mice. Coadministration of SJP effectively protected against bodyweight increase and lipid accumulation in blood and liver. Increased expression of PPARγ mRNA was observed in HFD feeding mice, but a steady elevation of PPARγ protein level was only found in SJP-treated mice. Meanwhile, the expression of FASN was much higher in HFD feeding mice. Microbiome analysis revealed obvious changes in gut microbiota composition among diverse groups. SJP treatment modulated the relative abundance of short-chain fatty acids (SCFAs) producing bacteria, including norank-f-Erysipelotrichaceae and Roseburia. Conclusions SJP is efficient in attenuating HFD-induced NAFLD, and it might be partly attributed to the regulation of gut microbiota.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is an alarming global health problem that is predicted to be the major cause of cirrhosis, hepatocellular carcinoma, and liver transplantation by 2030 [1, 2]
Compared with the control mice, we found a significant increase in peroxisome proliferator-activated receptor c (PPARc) mRNA expression in high-fat diet (HFD) feeding mice with/without Sheng-Jiang Powder (SJP) treatment, but there was no statistical difference in sterol regulatory element-binding protein 1c (SREBP1c) mRNA expression among diverse groups
Increased expression of PPARc mRNA was observed in HFD feeding mice, but a steady elevation of PPARc protein level was only found in SJP-treated mice
Summary
Nonalcoholic fatty liver disease (NAFLD) is an alarming global health problem that is predicted to be the major cause of cirrhosis, hepatocellular carcinoma, and liver transplantation by 2030 [1, 2]. The relationship of gut microbiota and NAFLD might be bidirectional as substantial evidences have disclosed obvious alterations in the composition of gut microbiota in NAFLD patients and mice compared to that of healthy individuals [16, 17] All these discoveries highlighted the critical role of gut microbiota in the development of NAFLD and pointed out the potential of a gut microbiota-targeted therapeutic strategy. As a classic representative traditional Chinese medicine formula, Sheng-Jiang Powder (SJP) showed satisfying clinical effect in treating NAFLD with confirmed wide ranging of pharmacological effects, such as anti-inflammation, lowering body weight, mitigating insulin resistance, and regulating immune response [23]. Considering the critical role of gut microbiota on the development of NAFLD, the present study was designed to explore the effect of SJP on gut microbiota by using a mice model of NAFLD
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