The Protective Effects of a Modified Xiaohua Funing Decoction against Acute Liver Failure in Mice Induced by D-Gal and LPS

Abstract

Objective. The aim of this study was to evaluate the effects of a modified Xiaohua Funing decoction (Xfd) on acute liver failure (ALF) and determine whether the protective mechanisms are related to alterations in the gut microbiota. Methods. An animal model of ALF was induced by intraperitoneal injection of D-galactosamine (D-Gal, 0.5 g/kg) and lipopolysaccharide (LPS, 100 μg/kg). Male BALB/c mice were randomly divided into the following 4 groups: the control group (saline, Con), model group (D-Gal/LPS, Mod), silymarin pretreatment group (200 mg/kg, Sil), and modified Xfd pretreatment group (650 mg/kg, Xfd). The Sil and Xfd groups received the respective intervention orally for 14 days and 2 h before D-Gal/LPS treatment. The liver injury markers included alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and liver histology. 16S rRNA gene sequencing was performed to assess the effects on the caecum content. Results. D-Gal/LPS treatment caused severe ALF, illustrating that the ALF model was successfully established. The administration of Sil and Xfd greatly reduced the serum ALT and AST levels and improved the pathological signs of liver injury. However, no significant difference was found between the two groups. In contrast to the Mod group, the Sil and Xfd groups showed a shift toward the Con group in terms of the gut microbiota structure. The abundances of Firmicutes and Bacteroidetes and the Bacteroidetes/Firmicutes ratio in the Mod group significantly differed from those in the Con group. The Sil and Xfd groups showed restoration of the disordered microbiota. Significantly increased relative abundances of Lachnospiraceae_NK4A136_group and Candidatus_Saccharimonas and a markedly decreased Muribaculaceae abundance were found in the Sil and Xfd mice compared with those in the Mod mice ( P < 0.01 , P < 0.05 ). Interestingly, a negative correlation was observed between the abundances of the gut microbiota constituents, specifically Clostridia_UCG-014, and ALT and AST levels. Conclusion. In summary, our results indicate that Xfd may protect the liver and modify the gut microbiota in ALF mice.

Integrated Microbiome and Metabolome Analysis Reveals Correlations Between Gut Microbiota Components and Metabolic Profiles in Mice with Methotrexate-Induced Hepatoxicity

“… 22 In addition, the abundance of Firmicutes was significantly decreased and the abundance of Bacteroidota was increased in a study of mice with acute liver failure. 23 These diverse results indicate that the liver injury caused by different approaches may be associated with different changes in gut microbiota components. Our results show that MTX treatment induced increased abundances of Firmicutes, Actinobacteriota , and Proteobacteria , but a significant reduction in the abundance of Bacteroidota .…”

Effects of Dietary Alfalfa Meal Supplementation on the Growth Performance, Nutrient Apparent Digestibility, Serum Parameters, and Intestinal Microbiota of Raccoon Dogs (Nyctereutes procyonoides)

“…Therefore, we speculated that the decline in Bacteroidota might arise from competition for nutrients or energy with the faster-growing fiber-degrading bacteria in Firmicutes [47]. Clostridia_UCG-014 negatively correlates with liver function indicators, particularly ALT levels [48]. We found that the serum ALT levels in raccoon dogs gradually decreased with the increase in alfalfa meal intake.…”

Gut microbes combined with metabolomics reveal the protective effects of Qijia Rougan decoction against CCl4-induced hepatic fibrosis

“…A prospective cohort study found that negativicutes are enriched, and Clostridia is significantly reduced in NAFLD-cirrhosis probands ( Oh et al, 2020 ). Clostridia UCG 014 exhibits an inverse correlation with ALT and AST levels in acute hepatic failure experiments, indicating its potentially beneficial effect on liver health ( Zhao et al, 2022 ). In this study, the abundance of gram-negative bacteria significantly increased, and that of beneficial bacteria uncultured rumen bacterium (belonging to Clostridia UCG 014, Clostridia ) decreased post CCl 4 induction.…”