The protective role of hydrophilic tetrahydroxylated bile acids (THBA)

Bile acids are key components of bile required for human health. In humans and mice, conditions of reduced bile flow, cholestasis, induce bile acid detoxification by producing tetrahydroxylated bile acids (THBA), more hydrophilic and less cytotoxic than the usual bile acids, which are typically di- or tri-hydroxylated. Mice deficient in the Bile Salt Export Pump (Bsep, or Abcb11), the primary bile acid transporter in liver cells, produce high levels of THBA, and avoid the severe liver damage typically seen in humans with BSEP deficiencies. THBA can suppress bile acid-induced liver damage in Mdr2-deficient mice, caused by their lack of phospholipids in bile exposing their biliary tracts to unbound bile acids. Here we review THBA-related works in both animals and humans, and discuss their potential relevance and applications as a class of functional bile acids. • Hydroxylation of bile acids is a common mechanism for detoxifying bile acid. • Species, including humans, differ in bile acid hydroxylation under cholestatic stress. • Tetrahydroxylated bile acids (THBA) are hepatoprotective, low-toxic, bile acids. • THBA can suppress bile acid induced liver damage in mice. • Human CYP450 enzymes cannot produce large quantities of THBA.