Abstract
Liver fibrosis often appears in chronic liver disease, with extracellular matrix (ECM) deposition as the main feature. Due to the presence of the liver-gut axis, the destruction of intestinal homeostasis is often accompanied by the development of liver fibrosis. The inconsistent ecological environment of different intestinal sites may lead to differences in the microbiota. The traditional Chinese medicine ursolic acid (UA) has been proven to protect the liver from fibrosis. We investigated the changes in the microbiota of different parts of the intestine during liver fibrosis and the effect of UA on these changes based on high-throughput sequencing technology. Sequencing results suggest that the diversity and abundance of intestinal microbiota decline and the composition of the microbiota is disordered, the potentially beneficial Firmicutes bacteria are reduced, and the pathways for functional prediction are changed in the ilea and anal faeces of liver fibrosis mice compared with normal mice. However, in UA-treated liver fibrosis mice, these disorders improved. It is worth noting that the bacterial changes in the ilea and anal faeces are not consistent. In conclusion, in liver fibrosis, the microbiota of different parts of the intestines have different degrees of disorder, and UA can improve this disorder. This may be a potential mechanism for UA to achieve anti-fibrosis. This study provides theoretical guidance for the UA targeting of intestinal microbiota for the treatment of liver fibrosis.
Highlights
Hepatic fibrosis often appears in chronic liver disease, with extracellular matrix (ECM) deposition as its main feature[1]
We show that Ursolic acid (UA) can improve the disorder of intestinal microbiota during liver fibrosis
Based on the latest generation of high-throughput sequencing technology, we have investigated the changes in the intestinal microbiota across different anatomic sites of the mouse intestinal tract
Summary
Mice in the control group were gavaged with olive oil (2 ml/kg) twice a week for 8 weeks. Mice in the CCl4 group were gavaged with carbon tetrachloride (CCl4) (1:4 diluted in olive oil, 2 ml/kg) twice a week for 8 weeks. Mice in the UA group were gavaged with CCl4 for 4 weeks and with UA (40 mg/kg/day) and CCl4 at the same time for the last 4 weeks.
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