Skip to main content

Dysbiosis of the microbiota in neurocritically ill patients associated with coma and death: ammonia as a potential missing link

Xu et al. conclude that changes in gut microbiota in neurocritically ill patients seem to have an impact on their mortality [1]. We would like to add some comments. The authors described an overgrowth of opportunistic pathogens defined as dysbiosis in patients with neurocritical illness. This study had similar results to other studies regarding the appearance of pathogens and disappearance of commensals [2, 3]. Further, the authors said that dysbiosis of the microbiota in neurocritical patients can be reasonably presumed to increase the risk of infection, undernutrition, and unconsciousness [1]. Here we would like to link dysbiosis and unconsciousness, where increased production of ammonia may play an important role. Indeed, bacteria residing in the human gut produce urease which is beneficial in healthy hosts but pathogenic in hosts with liver disease [4]. Urea produced by the liver is both excreted in urine and transported into the colon, where it is hydrolyzed by bacterial urease into carbon dioxide and ammonia [4]. Circulating ammonia is correlated with brain damage in patients with acute or chronic liver disease resulting in hepatic encephalopathy. In Xu’s study, nearly 40% of the patients had liver disease [1]. It is somewhat unfortunate that blood ammonia was not measured. This would have been of great utility to better interpret the results of their study [1, 4].

Xu also suggested that critical illness could lead to microbial translocation, potentially explaining the association between specific pathogens and mortality [1]. Another valid explanation, knowing that there was an overgrowth of enterobacteriaceae in this study [1], could be the translocation of endotoxin [5]. Indeed, translocation of endotoxin can trigger sepsis, septic shock, and secondary peritonitis [5]. This may have been an important contributing factor in this study, particularly in the 40% of patients who had liver disease [1] and therefore were less capable of filtering endotoxin [1, 5]. Measurement of endotoxin levels could be a useful addition in further studies.

Availability of data and materials

Not applicable.

Abbreviations

ICU:

Intensive care unit

References

  1. 1.

    Xu R, Tan C, Zhu J, Zeng X, Gao X, Wu Q, Chen Q, et al. Dysbiosis of the intestinal microbiota in neurocritically ill patients and the risk for death. Crit Care. 2019;23(1):195. https://doi.org/10.1186/s13054-019-2488-4.

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    McDonald D, Ackermann G, Khailova L, Baird C, Heyland D, Kozar R, et al. Extreme dysbiosis of the microbiome in critical illness. mSphere. 2016;1(4):e00199–16.

    CAS  Article  Google Scholar 

  3. 3.

    Freedberg DE, Zhou MJ, Cohen ME, Annavajhala MK, Khan S, Moscoso DI, et al. Pathogen colonization of the gastrointestinal microbiome at intensive care unit admission and risk for subsequent death or infection. Intensive Care Med. 2018;44(8):1203–11.

    Article  Google Scholar 

  4. 4.

    Shen TC, Albenberg L, Bittinger K, Chehoud C, Chen YY, Judge CA, et al. Engineering the gut microbiota to treat hyperammonemia. J Clin Invest. 2015;125(7):2841–50. https://doi.org/10.1172/JCI79214 Epub 2015 Jun 22.

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Iacob S, Iacob DG. Infectious threats, the intestinal barrier, and its Trojan horse: dysbiosis. Front Microbiol. 2019;10:1676. https://doi.org/10.3389/fmicb.2019.01676 eCollection 2019.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank a lot Dr. Melissa Jackson (native English colleague) for the critical editing of the manuscript.

Funding

None.

Author information

Affiliations

Authors

Contributions

PMH and DDB designed the paper. All authors participated in the drafting and reviewing. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Patrick M. Honore.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This comment refers to the article available at https://doi.org/10.1186/s13054-019-2488-4.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Honore, P.M., Mugisha, A., Barreto Gutierrez, L. et al. Dysbiosis of the microbiota in neurocritically ill patients associated with coma and death: ammonia as a potential missing link. Crit Care 23, 403 (2019). https://doi.org/10.1186/s13054-019-2688-y

Download citation