Changes and Correlations of the Intestinal Flora and Liver Metabolite Profiles in Mice With Gallstones.

Yang Chen,Dongbo Xue,Wenqi Gao,Biao Ma,Chenjun Hao,Qiang Wang

doi:10.3389/fphys.2021.716654

Abstract

There is increasing appreciation for the roles of the gut-liver axis in liver and gall diseases. Specific gut microbes are associated with susceptibility to gallstone diseases, while the relationship between intestinal flora and liver metabolism in the formation of gallstones remains unclear. In this study, an experimental group of model mice was given a lithogenic diet, and a control group was given a normal diet. Both groups were fed for 8 weeks. Integrating 16S rRNA gene sequencing and non-targeted metabolomics to explore the impact of the lithogenic diet on intestinal flora and liver metabolism, Spearman correlation analysis reveals the network of relationships between the intestine and liver. Our findings showed that the gut microbiome and liver metabolome compositions of the test group were significantly changed compared with those of the normal group. Through our research, biomarkers of gallstones were identified at the phylum (5), class (5), order (5), family (7), and genus levels. We predicted the function of the differential flora. We analyzed the liver metabolism of mice with gallstones paired with their flora, and the results showed that there were 138 different metabolites between the two groups. The metabolic pathways enriched by these differential metabolites are highly consistent with the functions of the disordered flora. We focused on an analysis of the relationship between deoxycholic acid, asymmetric dimethylarginine, glucosamine, tauroursodeoxycholic acid, and the disordered flora. This provides a basis for the establishment of the intestine-liver axis in gallstone disease. This research provides a theoretical basis for the research and development of probiotics and prebiotics.

Highlights

Gallstones are very common worldwide and affect 10–20% of the global adult population (Lammert et al, 2016)
After 8 weeks of dietary intervention, as expected, cholesterol gallstones were observed in all mouse gallbladders of the T group, and cholesterol crystals were confirmed by polarizedlight microscopy, while no cholesterol gallstones or crystals were found in the C group either by gross observation or polarized-light microscopy
This study confirmed that mice with gallstones have severe intestinal flora imbalance, and these disordered flora will not recover without intervention

Summary

Introduction

Gallstones are very common worldwide and affect 10–20% of the global adult population (Lammert et al, 2016). Due to improved lifestyles and increased consumption of fat- or cholesterolrich diets, the prevalence of gallstone disease has increased rapidly. The treatment for gallstone disease remains predominantly invasive; cholecystectomy potentially generates health problems, including intestinal dysfunction (Di Ciaula et al, 2019) and even increased colon cancer risk (Chen et al, 2014, 2020; Shabanzadeh et al, 2017). Future efforts should focus on preventive strategies to prevent the formation of gallstones. Intestinal factors leading to the formation of cholesterol gallstones include reduced absorption of bile salt and increased absorption of cholesterol. The intestinal flora, as an intestinal factor, plays an important role in the formation of gallstones

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Results

Discussion

Conclusion