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Licensed Unlicensed Requires Authentication Published by De Gruyter March 21, 2022

Determination of individual bile acids in acute respiratory distress syndrome reveals a specific pattern of primary and secondary bile acids and a shift to the acidic pathway as an adaptive response to the critical condition

  • Lars-Olav Harnisch ORCID logo EMAIL logo , Diana Mihaylov , Thomas Bein , Christian Apfelbacher , Michael Kiehntopf , Michael Bauer , Onnen Moerer and Michael Quintel



Cholestasis and elevated serum bile1 acid levels are common in critically ill patients. This study aims to define the specific pattern of bile acids associated with acute respiratory distress syndrome (ARDS) and the changes in pattern over time.


Prospective observational study. Serum samples of 70 ARDS patients were analyzed for primary bile acids (cholic acid, chenodeoxycholic acid) and secondary bile acids (deoxycholic acid, litocholic acid, and ursodeoxycholic acid) as well as their glycine and taurine glycation products.


Primary bile acid levels increased from day zero to day five by almost 50% (p<0.05). This change bases on a statistically significant increase in all primary bile acids between day 0 and day 5 (cholic acid [CA] p=0.001, taurocholic acid [TCA] p=0.004, glycocholic acid [GCA] p<0.001, chenodeoxycholic acid [CDCA] p=0.036, taurochenodeoxycholic acid [TCDCA] p<0.001, glycochenodeoxycholic acid [GCDCA] p<0.001). Secondary bile acids showed predominantly decreased levels on day 0 compared to the control group and remained stable throughout the study period; the differences between day zero and day five were not statistically significant. Non-survivors exhibited significantly higher levels of TCDCA on day 5 (p<0.05) than survivors. This value was also independently associated with survival in a logistic regression model with an odds ratio of 2.24 (95% CI 0.53–9.46).


The individual bile acid profile of this ARDS patient cohort is unique compared to other disease states. The combination of changes in individual bile acids reflects a shift toward the acidic pathway of bile acid synthesis. Our results support the concept of ARDS-specific plasma levels of bile acids in a specific pattern as an adaptive response mechanism.

Corresponding author: Dr. med. Lars-Olav Harnisch, MD, DESA, EDIC, Department of Anaesthesiology, Georg-August University of Göttingen, Robert-Koch-Str. 40, Göttingen, 37099, Germany, Phone: +49 551 39 63579, Fax: +49 551 39 13329, E-mail:

1Bile acid conjugates exist predominantly in their anionic form at physiological pH; therefore, they are called bile salts. For a matter of simplicity, we will name both forms (ionic as well as anionic) bile acids in this article.


This research was facilitated by a generous unrestricted grant from Sartorius AG, Göttingen.

  1. Research funding: The study was fully funded by departmental funding from the Göttingen and Jena Centers.

  2. Author contributions: LOH initiated the trial, consented the patients, took the specimen and clinical data, condensed and analyzed the data and drafted and revised the manuscript. DM analyzed the specimen, helped with the analysis of the data, and revised the manuscript. TB and CA initiated the DACAPO trial, helped with study initiation, and revised the manuscript. MK supervised and helped to analyze the specimen, helped to analyze and interpret the data and revised the manuscript. MB helped initiating the trial and interpreting the data and revised the manuscript. OM helped analyzing and interpreting the data and revised the manuscript. MQ helped initiate the trial, analyze the data, and revised the manuscript. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: LOH received non-cash benefits from CSL Behring for advanced trainings, advisory fees from Baxter, and an unrestricted research Grant from Sartorius AG Göttingen. DM reports no conflicts of interest and did not receive any benefits. TB, CA, MK, MB: no conflicts of interest. OM received honoraria for lectures during workshops on hemodynamic monitoring, supported by Pulsion (Maquet Critical Care) and for 2 lectures during industrial sessions at national congresses (HillRom, Hepawash); unrestricted research grant from CSL Behring in 2015. MQ: Advisory Board Xenios/Fresenius, Advisory Board Baxter, Advisory Board B. Braun, member of DSMB for a study conducted by Bayer.

  4. Informed consent: Informed consent to participate and for publication was obtained from patients where possible, otherwise next of kin/legal representatives.

  5. Ethical approval: The study was approved by the local Research Ethics Board of Georg-August-University Goettingen (IRB No. 18/8/14 on 08.09.2014).

  6. Data availability: Data are available upon reasonable request from the corresponding author.

  7. Trial registration:, NCT02637011. Registered 15 December 2015,;NCT02637011&draw=0;2&rank=0;1.


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Supplementary Material

The online version of this article offers supplementary material (

Received: 2021-11-06
Revised: 2022-03-04
Accepted: 2022-03-04
Published Online: 2022-03-21
Published in Print: 2022-05-25

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