Modulation of bile acid profile by gut microbiota in chronic hepatitis B

Abstract

Chronic hepatitis B (CHB) is a global epidemic disease that may progress to fibrosis, cirrhosis and hepatocellular carcinoma. The role of the liver‐bile acid‐microbiota axis in CHB remains unclear. The aims of this study are to elucidate the alteration of the gut microbiota and its functions in bile acid homeostasis in CHB patients with different degrees of fibrosis. In the present study, we evaluated serum and faecal bile acid profiles in healthy controls and CHB patients with biopsy‐proven diagnosis: patients had stage 0‐1 fibrosis were classified as mild CHB and patients had stage 2‐4 fibrosis were classified as moderate/advanced CHB. The levels of serum total bile acids (BAs) and primary BAs were increased in CHB patients with moderate/advanced fibrosis, whereas faecal total and secondary BAs levels were significantly lower. Analyses of gut microbiota exhibited a trend of decreased abundance in bacteria genera responsible for BA metabolism in CHB patients with moderate/advanced fibrosis. CHB is associated with altered bile acid pool which is linked with the dysregulated gut microbiota. The higher level of FGF‐19 may act in a negative feedback loop for maintaining the bile acid homeostasis.

Western Diet Aggravated Carbon Tetrachloride‐Induced Chronic Liver Injury by Disturbing Gut Microbiota and Bile Acid Metabolism

“…In addition, a lower fecal DCA/CDCA ratio has been suggested to reflect the activation of FXR in the ileum. [ 30 ] Consistently, the upregulated fecal CDCA and downregulated fecal DCA/CDCA ratio in the WC group could activate ileal FXR, which induced FGF15 secretion, as evidenced by the higher serum FGF15 concentration in this study. Interestingly, FGF15 deficiency has been confirmed to alleviate CCL 4 ‐induced liver fibrosis by activating CTGF, which results in the activation of hepatic stellate cells.…”

“…The ratio of DCA to CDCA is thought to reflect the activation of FXR, which influences the secretion of FGF19 (FGF 15 is the mouse ortholog). [ 30 ] In our study, a decreased ratio of DCA to CDCA was observed in CCL 4 + WD‐treated mice (Figure 8F, CC vs WC p < 0.05). To verify our results, we detected the serum levels of FGF15 and found that they were upregulated dramatically in the WC group, which was consistent with the change in the ratio of DCA to CDCA (Figure 8G).…”

“…[ 32 ] The close relationship among CLD, gut microbiota, and BAs has been extensively investigated. [ 6,7,30,33 ] In addition, the influence of dietary practices on modulating the gut microbiota and BAs has been confirmed in previous studies. [ 32,18 ] However, whether WD influences the progression of CLD, and the role of gut microbiota and BA metabolism in the mechanism are still worth further exploration.…”

Gut Microbiota in Metabolic-associated Fatty Liver Disease and in Other Chronic Metabolic Diseases

“…17,44 BAs represent a crucial partaker in liver-microbiota communication, and their composition and concentration seem to have a positive correlation with metabolism and hepatic fibrosis. 45,46 The composition of BAs is important in many metabolic diseases, it has been described that patients with T2DM present a change from PBA to SBA with an increase in deoxycholic acid levels. BAs are metabolic integrators that act through signaling pathways that regulate the expression of certain metabolic genes; hence, a tweak in BA signaling might promote and aggravate metabolic syndrome.…”

Advances in the Involvement of Gut Microbiota in Pathophysiology of NAFLD

“…Bile acid acyl-CoA-synthetase (BACS), which catalyzes taurine conjugation in BAs in the liver and apical bile acid transporters in the ileum, were downregulated in CONV-R mice ( 53 ). In a human study for chronic hepatitis B, the levels of total and primary BAs (TCDCA, GCDCA, GCA, and TCA) were upregulated in hepatitis B patients with moderate/advanced fibrosis, accompanied with downregulation of gut microbiota (such as Bacteroides and Ruminococcus) responsible for BAs metabolism ( 54 ). Trimethylamine N-oxide (TMAO), which is a metabolite produced by gut microbiota from choline, stimulated the expression of CYP7A1 in the liver, increased the serum levels of BAs and promoted FXR-antagonistic BAs ( 55 ).…”