Plasma Bile Acid Concentrations in Humans: Suggestions for Presentation in Tabular Form.

Abstract

Potential conflict of interest: Nothing to report. TO THE EDITOR: The development of liquid chromatography/mass spectrometry measurement of plasma bile acids has resulted in recent studies showing the complexity of the plasma bile acid profile in health and disease. As an example, a recent paper by Puri et al.1 presents heat map data for 23 bile acids. The purpose of this letter is to propose a format for bile acid data that are to be presented in tabular form, as well as to provide an explanation for this proposal. Bile acid quantification using mass spectrometry is best done by having deuterium labeled bile acids as internal standards. In addition, detector response to a stepwise increase in concentration of reference bile acids is necessary. Failing these requirements, one is uncertain about the accuracy of the measurements. Nonetheless, changes with time in a given subject or between treatment groups can provide useful information. 1. Inclusion: Bile acids present at less than 5% of total bile acids should be excluded from data analysis and listed in a footnote to the table, unless there is a special interest in a minor bile acid. 2. Total bile acids: This is the sum of both conjugated bile acids (originating from carrier mediated absorption from the distal small intestine) plus unconjugated bile acids formed by bacterial deconjugation in the intestine. As plasma bile acids have half‐life of only a few minutes, the level of total bile acids is determined by the rate of intestinal absorption in relation to net hepatic uptake. The measurement also permits comparison with the older literature in which total bile acids were measured by enzymatic analysis, gas chromatography, or competitive binding assays. 3. Total unconjugated bile acids: The value is determined by the rate of intestinal absorption of unconjugated bile acids, formed by bacterial deconjugation in relation to hepatic uptake. Absorption from the intestine may be passive or carrier mediated, or both. By dividing 3 by 2, (and multiplying by 100) one has the % of bile acids in unconjugated form. Individual bile acids 4. Cholyl conjugates: This is the sum of glycocholate and taurocholate. The proportion of bile acidsconjugated with taurine depends on the taurine concentration in the hepatocyte and is not connected to bile acid metabolism per se. 5. Cholate (or unconjugated cholic acid) is determined by the rate of absorption from the distal intestine in relation to hepatic uptake. Dividing 5 by 4+5 gives the % of the cholyl “family” in unconjugated form. 6. Chenodeoxycholyl conjugates. See explanation for4. 7. Chenodeoxycholate (or unconjugated chenodeoxycholic acid or chenodiol). See category 5. 8. Deoxycholyl conjugates. See explanation for category 4. Deoxycholyl conjugates are the major secondary bile acids in humans. 9. Deoxycholate (or unconjugated deoxycholic acid) See category 5. This approach should also be applicable to animals in which hydroxylation at carbon number 6 occurs. These are hyocholate (3α, 6α, 7α‐ trihydroxy) and the muricholate family. It is hoped that these suggestions that decrease the number of parameters to 8 (or 10 in patients ingesting ursodeoxycholic acid) will help make plasma bile acid levels easier to grasp by newcomers to the field of bile acids.