Could lung bacterial dysbiosis predict ICU mortality in patients with extra-pulmonary sepsis? A proof-of-concept study
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LETTER
Could lung bacterial dysbiosis predict ICU mortality in patients with extra‑pulmonary sepsis? A proof‑of‑concept study Sepsis Lung Microbiome Study Group* © 2020 Springer-Verlag GmbH Germany, part of Springer Nature
Dear Editor, Sepsis is a major cause of mortality worldwide [1]. However, prognosis in these critically ill patients is based on severity scores, in combination with plasma biomarkers, which have shown a limited power to predict patient severity; thus, novel and more accurate biomarkers are needed [2]. Alterations of the microbial diversity (commonly known as dysbiosis) have been linked to sepsis development and severity [3–6]. Interestingly, enrichment of gut bacteria in the lung microbiome has been found in patients with sepsis and acute respiratory distress syndrome (ARDS), likely by translocation of intestinal microbes [7]. However, although it is known that the lung microbiome is severely altered in critically ill patients [5, 8], a specific association of the lung dysbiosis with sepsis mortality remains to be determined. Here we performed a prospective study to assess the lung dysbiosis in a cohort of 36 mechanically ventilated adult patients diagnosed with extrapulmonary sepsis (avoiding the potential confounder effects of pneumonia in the lung dysbiosis). Among them, 29 were discharged alive from the intensive care unit (ICU), and seven patients died while admitted to the ICU (Table S1). Tracheal aspirate samples were collected from these patients at three different time-points while the patients remained intubated: within the first 8 h of sepsis diagnosis, and at 48 h and 72 h after sepsis onset. Bacterial genera were obtained by DNA sequencing of the 16S rRNA gene, and bacterial diversity was correlated with *Correspondence: [email protected] The members of the Sepsis Lung Microbiome Study Group are listed in the Acknowledgements.
ICU mortality. Results focused on the Shannon Diversity Index, although a high correlation with alternative diversity indices was found (Table S2). Orthogonal validation of the dysbiosis was assessed with another sequencing technology and analysis pipeline. Complete details are provided in the online supplement. Bacterial diversity did not vary significantly among the three collection times (p = 0.99) (Fig. S1, Table S3). Diversity and abundance estimates in the lung bacterial communities were compared between patients who were discharged alive from the ICU and those who died during the ICU stay. Bacterial diversity decreased significantly in the deceased compared to surviving patients within 8 h of sepsis diagnosis (Shannon Diversity Index, p = 0.001) (Fig. 1a). The orthogonal validation with the MinION sequencer (Oxford Nanopore Technologies, Oxford, UK) based on the full-length 16S rRNA gene sequencing confirmed this reduction in the bacterial diversity (Shannon Diversity Index, p = 0.029). A sensitivity analysis was performed to evaluate the effect of possible confounding variables, and we observed that association results did not vary significa
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