Bile Acid Metabolism in Health and Disease

Alternating Dual-Collision Energy Scanning Mass Spectrometry Approach: Discovery of Novel Microbial Bile-Acid Conjugates

“…The distribution and detailed information on these detected BAs are presented in Table S5 in Supporting Information-2. The varieties of BAs detected from mouse intestine contents and feces were far more abundant than those from liver and intestine tissues of mice, which was consistent with the fact that gut microbiota mediate the synthesis of BAs. − …”

“…Primary BAs are synthesized by hepatocytes via multistep enzymatic reactions of cholesterol, and further conjugated (amidated) with glycine or taurine. − After release into the small intestine, BAs undergo gut microbiota metabolisms including deconjugation, dehydroxylation, dehydrogenation, and epimerization to produce secondary BAs (such as DCA, HCA, HDCA, LCA, α-MCA, and MDCA). − Very recently, Quinn et al discovered three novel amino acid conjugates of BAs (phenylalanine, tyrosine, and leucine conjugates of cholic acid) in the gastrointestinal tract of SPF mice and revealed that these newly discovered BA conjugates are biosynthesized in the intestine under mediation of gut microbiota, and they serve as signal molecules to stimulate FXR receptors and inhibit the expression of FXR target genes in mice . Their results suggest that gut microbial metabolism can enrich the diversity and composition of the BA pool .…”

Fibrotic Events in the Progression of Cholestatic Liver Disease

“…Approximately 95% of PBC patients are middle-aged women [ 27 ]. Interestingly, this disease rarely affects children [ 28 ].…”

“…Clinical manifestations reflect the potential sequence of bile duct injury and fibrosis leading to stricture, cholestasis, and biliary cirrhosis with progressive liver dysfunction [ 50 ]. PSC is a male-dominant disease when it is associated with inflammatory bowel disease (IBD), (65–70%), with a male-female ratio of approximately 2:1 [ 27 , 51 , 52 , 53 ]. Epidemiological studies show that the prevalence of PSC is about 1/10,000 cases globally, while the incidence rate in northern Europe and the United States is 0.4/100,000 to 2.0/100,000 per year [ 54 , 55 ].…”