Intestinal flora imbalance affects bile acid metabolism and is associated with gallstone formation

Abstract

Background: The gut microbiota participates in the metabolism of substances and energy, promotes the development and maturation of the immune system, forms the mucosal barrier, and protects the host from pathogen attacks. Although the pathogenesis of cholesterol gallstones is still not clear, studies have suggested that gut microbiota dysbiosis plays an important role in their formation. Methods: Microbial DNA from faeces of normal control patients and those of patients with calculi was subjected to 16S rRNA gene sequencing to detect gene expression changes in intestinal microbes. ELISA kits were used to measure free bile acids, secondary bile acids and coprostanol according to the manufacturer’s instructions. The relationship between flora and their metabolites was then analysed. Results: In the gallstone group, the diversity of intestinal bacteria and the abundances of certain phylogroups were significantly decreased (p<0.05), especially Firmicutes (p<0.05), the largest phylum represented by the gut microbiota. This study found an increase in free bile acids (p<0.001) and secondary bile acids (p<0.01) in the enterohepatic circulation. Bile salt hydrolase activity was not related to the abundances of BSH-active bacteria. 7a-dehydroxylating gut bacteria were significantly increased (p<0.01), whereas cholesterol-lowering bacteria were significantly reduced (p<0.05). The Ruminococcus gnavus group could be used as a biomarker to distinguish the gallstone group from the control group. Conclusion: We conclude that intestinal flora imbalance affects bile acid and cholesterol metabolism and is associated with gallstone formation.

Aqueous Extract of Lysimachia christinae Hance Prevents Cholesterol Gallstone in Mice by Affecting the Intestinal Microflora

“…The role of Verrucomicrobia in the mechanism of gallstone formation needs further study. Many previous studies have shown similar results [30][31][32], but here, there is something different: former studies have found that the most abundant phylum in all groups was Firmicutes [33]. In this study, Bacteroidetes was the primary intestinal microflora in the CK group, but Verrucomicrobia increased to reach almost the same level as Bacteroidetes, and these two phyla became dominant in the remaining four groups.…”

Adipose Tissue, Bile Acids, and Gut Microbiome Species Associated With Gallstones After Bariatric Surgery

“…The prevalence of patients forming gallstones rather decreases in the second year after surgery. In patients with gallstones after bariatric surgery, we observed a higher abundance of Ruminococcus gnavus, a microbe that was recently identified as a biomarker for gallstones (9). Further, fecal metagenomic shotgun sequencing revealed higher abundance of Lactobacillaceae and Enterobacteriaceae in patients without gallstones.…”

“…Factors associated with gallstone formation in the general population include decreased secretion of bile acids, hypersecretion of cholesterol, rapid phase transitions of cholesterol in bile leading to the precipitation of cholesterol crystals, and impaired gallbladder motility with hypersecretion of mucus (5). Furthermore, gut microbiome has also been suggested as one of the drivers of cholesterol gallstone formation and can influence bile acid metabolism via conversion of primary bile acids into secondary bile acids in the gut (6)(7)(8)(9).…”

Alleviation of Cholesterol Gallstones by Lactobacillus Targeting the Gut Microbiota Depends on Global Farnesoid X Receptor-Mediated Bile Acid Metabolism

“…The amount of secondary BAs was dependent on primary BA deconjugation and subsequent conversion by the gut microbiota [27]. The conversion of conjugated BAs converted to deconjugated BAs is dependent on gut microbiota catalyzing the reaction [51]. Furthermore, the conjugated BAs will inhibit the growth of gut microbiota.…”

“…Gut microbiota dysbiosis and bacterial community assembly were associated with cholesterol gallstones in a large-scale study [5][6][7]. It has been reported that the proportion of Lactobacillus is greatly reduced in CGS mouse models [8]; however, whether Lactobacillus supplementation can reduce gallstones has not been studied.…”