Bile acids associate with specific gut microbiota, low‐level alcohol consumption and liver fibrosis in patients with non‐alcoholic fatty liver disease

Abstract

Background: Bile acids (BAs) are synthesized by the liver and modified by gut bacteria, and may play an intermediary role between the gut microbiome and liver in promoting fibrosis in non-alcoholic fatty liver disease (NAFLD). We investigated the associations between serum and faecal BAs, gut microbiome and fibrosis in patients with and without NAFLD and examined the impact of diet and alcohol consumption on these relationships. Methods: Adult patients (n = 122) underwent liver biopsy and BAs characterization by high-performance liquid chromatography/mass spectrometry. Gut microbiome composition was analysed using next-generation 16S rRNA sequencing. Diet and alcohol intake were determined by 3-day food diary. Results: Serum and faecal BA concentrations increased progressively among non-NAFLD controls (n = 55), NAFLD patients with no/mild fibrosis (F0-2, n = 58) and NAFLD with advanced fibrosis (F3/4, n = 9). Progressive increases in serum BAs were driven by primary conjugated BAs including glycocholic acid [GCA] and secondary conjugated BAs. In contrast, faecal BA increase was driven by secondary unconjugated BAs (predominately deoxycholic acid [DCA]). Serum GCA levels and faecal DCA levels correlated with the abundance of Bacteroidaceae and Lachnospiraceae, and stool secondary BAs with an unclassifiable family of the order Bacteroidales (Bacteroidales;other). These bacterial taxa were also associated with advanced fibrosis. Modest alcohol consumption was positively correlated with faecal DCA levels and relative abundance of Lachnospiracaea and Bacteroidales;other. Conclusions: Higher serum and faecal BA levels are associated with advanced fibrosis in NAFLD. Specific gut bacteria link alterations in BA profiles and advanced fibrosis, and may be influenced by low-level alcohol consumption.

Secondary Sclerosing Cholangitis in Critically Ill Patients Alters the Gut–Liver Axis: A Case Control Study

“…When searching for factors that may connect dysbiosis and intestinal wall integrity in a cholestatic disease, bile acids need to be considered. Bile acids consist of steroid molecules and can be divided into primary bile acids, which are produced in the liver, and into secondary bile acids, which are the result of primary bile acids being metabolized by the gut microbiome [ 85 ]. This bile acid homeostasis is controlled by the intestinal microbiome [ 86 ].…”

Role of microbiota and related metabolites in gastrointestinal tract barrier function in NAFLD

“…195 The elevated synthesis of BAs and the previously mentioned higher sensitivity of Gram-positive bacteria to them could explain the decrease in the Ruminococcaceae clade. In contrast, Adams et al 196 associated a higher abundance of DCA with the abundance of the Lachnospiraceae family and advanced liver fibrosis. The increase in abundance of the Lachnospiraceae family could explain the increase in DCA levels since this clade has been shown to have bile acid-inducible 7α-dehydroxylation genes.…”

Metabolomics in Advanced Liver Disease

“…Adams et al (2019) examined the link between bile acid profiles, gut microbiome, and cirrhosis in patients with NAFLD. They showed an association between alteration in bile acid profiles and changes in the composition of specific microbiota taxa in advanced cirrhosis [38].…”