Polymicrobial sepsis causes deranged bile acid conjugation and transport.

<p>At 15 h after sepsis induction, plasma, liver tissue, and bile were subjected to targeted metabolomics. Expression of BAAT, facilitating conjugation to taurine and glycine, was quantified by immunoblotting. (A) The plot depicts median log₂ fold changes of unconjugated as well as glycine- and taurine-conjugated bile acid in plasma, liver, and bile, comparing septic to sham-operated rats (<i>n</i> = 12 per group, *<i>p</i><0.05 or **<i>p</i><0.01 compared to sham). (B) Conjugation index as a surrogate for the observed conjugation defect reflected by the ratio of unconjugated bile acids CA and CDCA to the corresponding taurine (TCA and taurochenodeoxycholic acid) and glycine (GCA and glycochenodeoxycholic acid) conjugates in plasma, liver and bile (ratio given as log₂ fold change, <i>n</i> = 12 per group). (C and D) Representative immunoblots of BAAT 15 h after sepsis induction in cytosolic (c) as well as peroxisomal (p) fractions, with corresponding densitometric analysis (<i>n</i> = 5 for sham, <i>n</i> = 8 for sepsis; BAAT (c): *<i>p</i> = 0.002; BAAT (p): *<i>p</i> = 0.006 compared to sham). Densitomentric values are normalised to β-actin. DCA, deoxycholic acid; GDCA, glycodeoxycholic acid; GCDCA, glycochenodeoxycholic acid; GLCA, glycolithocholic acid; GLCAS, glycolithocholic acid sulphate; GUDCA, glycoursodeoxycholic acid; TCDCA, taurochenodeoxycholic acid; TLCA, taurolithocholic acid; TLCAS, taurolithocholic acid sulphate; TUDCA, tauroursodeoxycholic acid; UDCA, ursodeoxycholic acid.