Alteration of gut microbiota in association with cholesterol gallstone formation in mice

Abstract

BackgroundThe gut microbiome exerts extensive roles in metabolism of nutrients, pharmaceuticals, organic chemicals. Little has been known for the role of gut microbiota in regulating cholesterol and bile acids in association with gallstone formation. This study investigated the changes in the composition of gut microbiota in mice fed with lithogenic diet (LD).MethodsAdult male C57BL/6 J mice were fed with either lithogenic diet (1.25% cholesterol and 0.5% cholic acid) or chow diet as control for 56 days. The fecal microbiota were determined by 16S rRNA gene sequencing.ResultsLD led to formation of cholesterol gallstone in mice. The richness and alpha diversity of gut microbial reduced in mice fed with LD. Firmicutes was significantly decreased from 59.71% under chow diet to 31.45% under LD, P < 0.01, as well as the ratio of Firmicutes to Bacteroidetes. Differences in gut microbiota composition were also observed at phylum, family and genus levels between the two groups.ConclusionOur results suggested that gut microbiota dysbiosis might play an important role in the pathogenesis of cholesterol gallstone formation in mice.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-017-0629-2) contains supplementary material, which is available to authorized users.

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

“…Wang et al [3] showed that gut microbiota at different levels changed with gallstone formation, indicating that gut microbiota dysbiosis plays an important role in the promotion of gallstone formation. Fremont-Rahl et al found that compared to the control group, the incidence rate of cholesterol gallstones in sterile mice fed LD significantly increased.…”

“…Most (90%) gallstones are cholesterol gallstones [2]. The pathogenesis of cholesterol gallstones is still not clear, though studies suggest that gut microbiota dysbiosis plays an important role in their formation [3]. 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 [4].…”

“…Current studies have shown that changes in gut microbiota are associated with the formation of cholesterol gallstones. Wang et al [3] investigated the faeces of mice with cholesterol gallstones using 16S ribosomal RNA (16 s rRNA) gene sequencing and found that in the intestinal tract of mice, the Firmicutes content and the Firmicutes/ Bacteroidetes (F/B) ratio decreased, the abundances and diversity of the microbiota also significantly decreased, and a lithogenic diet (LD) reshaped the abundances of gut microbiota at different levels. Keren et al found that in patients with gallstones, the microbial diversity was reduced and the total bile acid concentration in faeces was increased [8].…”

Pathophysiological connections between gallstone disease, insulin resistance, and obesity

“…Importantly, abnormal BAs pool composition is a proposed determinant for cancer in the proximal colon and rectum and pancreas as well as cholangiocarcinoma, inflammatory bowel disease, and metabolic syndrome . BAs composition influences the balance between bacterial populations in the intestine, such has been observed in mice fed a lithogenic diet and in patients with GSD who show decreased microbial diversity and dysbiosis . Importantly, although cholecystectomy results in a continuous cycling of BAs pool in the enterohepatic circulation; its impact on BAs pool composition is less clear.…”

Intestinal microbes affect bile acid metabolism involved in gallstone formation

“…Current studies have shown that changes in gut microbiota are associated with the formation of cholesterol gallstones. Wang et al [3] investigated the faeces of mice with cholesterol gallstones using 16S ribosomal RNA (16s rRNA) gene sequencing and found that in the intestinal tract of mice, the Firmicutes content and the Firmicutes/Bacteroidetes (F/B) ratio decreased, the abundances and diversity of the microbiota also significantly decreased, and a lithogenic diet (LD) reshaped the abundances of gut microbiota at different levels. Keren et al found that in patients with gallstones, the microbial diversity was reduced and the total bile acid concentration in faeces was increased [8].…”