Gut microbiota combined with metabolomics reveal the mechanism of curcumol on liver fibrosis in mice

Biomed Pharmacother. 2022 Aug:152:113204. doi: 10.1016/j.biopha.2022.113204. Epub 2022 May 30.

Abstract

Objective: Liver fibrosis is a reversible pathological process, and its prevention and treatment hold great significance for patients with chronic liver disease. This study combined 16S rRNA analysis of gut microbiota and serum metabolomics to explore the mechanism of curcumol's effect on liver fibrosis in mice. The results clarified the relationship between the gut microbiota and metabolites in the process of liver fibrosis.

Materials and methods: In this study, we randomly divided mice into a control group, a model group, and a curcumol treatment group to analyze the pathological changes in the liver tissue as well as the activities of the toll-like receptor 4 (TLR4)/nuclear factory kappa B (NF-κB) signaling pathway and inflammatory factors, such as tumor necrosis factor (TNF), interleukin 6 (IL-6), and IL-8. The gut microbiota were analyzed by 16 S rRNA sequencing, and serum metabolites were examined by liquid chromatography-mass spectrometry (LC-MS) metabolomic analysis.

Results: Molecular biological testing found that curcumol could significantly improve the pathological changes of the liver tissue and inhibit the occurrence of liver inflammation. Intestinal flora testing found that curcumol could significantly change the abundances of Veillonellaceae, Prerotella_oulorum, and Alistipes_finegoldii. Metabolomics analysis found that curcumol's antihepatic fibrosis effect may be related to its regulation of arachidonic acid metabolism. Correlation analysis suggested that curcumol regulated the abundances of Bacteroidota and Bacteroides and participated in the metabolism of Prostaglandin B2.

Conclusions: When liver fibrosis occurs, the intestinal flora and metabolic network are altered. The effect of curcumol on liver fibrosis may be related to its regulation of intestinal flora and the resulting interference with metabolic pathways, thereby reducing liver inflammation.

Keywords: Hepatic fibrosis; Intestinal microbiota; Metabolomics.

MeSH terms

  • Animals
  • Gastrointestinal Microbiome*
  • Humans
  • Inflammation
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / prevention & control
  • Metabolomics / methods
  • Mice
  • RNA, Ribosomal, 16S
  • Sesquiterpenes

Substances

  • RNA, Ribosomal, 16S
  • Sesquiterpenes
  • curcumol