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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.

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  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.

    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. 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. eCollection 2019.

    Article  PubMed  PubMed Central  Google Scholar 

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



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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.

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Correspondence to Patrick M. Honore.

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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).

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