Metagenomic Analysis Reveals Dynamic Changes of Whole Gut Microbiota in the Acute Phase of Intensive Care Unit Patients

Masahiro Ojima, Daisuke Motooka, Kentaro Shimizu, Kazuyoshi Gotoh, Ayumi Shintani, Kazuhisa Yoshiya, Shota Nakamura, Hiroshi Ogura, Tetsuya Iida, Takeshi Shimazu, Masahiro Ojima, Daisuke Motooka, Kentaro Shimizu, Kazuyoshi Gotoh, Ayumi Shintani, Kazuhisa Yoshiya, Shota Nakamura, Hiroshi Ogura, Tetsuya Iida, Takeshi Shimazu

Abstract

Background: Metagenomic analysis targeting the 16S rRNA gene has made it possible to characterize the vast array of microorganisms contained in the gut.

Aim: The purpose of this study was to evaluate how gut microbiota change in intensive care unit (ICU) patients in the acute phase after admission.

Methods: This prospective observational cohort study investigated 12 patients admitted to a single ICU of a large urban tertiary referral hospital. All patients were mechanically ventilated on admission. Fecal samples were collected from patients on days 1-2, 2-4, 5-8, and 7-10 after admission. DNA was extracted from fecal samples, and 16S rRNA deep sequencing was performed to monitor gut changes.

Results: Bacteria belonging to the phyla Firmicutes or Bacteroidetes were predominant in each sample. We observed serial dynamic changes in the percentages of Bacteroidetes and Firmicutes that were significantly altered during study period (p < 0.05). A ratio of Bacteroidetes to Firmicutes (B/F ratio) of >10 was seen in four of the six patients who died, whereas a B/F ratio of <0.10 was seen in only one of the six deaths. None of the survivors had a B/F ratio of >10 or <0.10. There was a statistical difference in the B/F ratio between the dead patients and survivors (p = 0.022).

Conclusions: Dynamic changes in gut microbiota at the phylum level of ICU patients during the acute phase were identified by high-throughput DNA sequencing. An extreme imbalance in gut microbiota may be associated with prognosis in critically ill patients.

Keywords: Bacteroidetes; DNA sequencing; Intensive care; Metagenome; Metagenomics; Microbiota; RNA, Ribosomal, 16S; Sepsis.

Figures

Fig. 1
Fig. 1
Taxonomic composition of the gut microbiota at the phylum level as determined by metagenomic analysis. Color coding: blue = Bacteroidetes, red = Firmicutes, green = Proteobacteria, orange = Actinobacteria, yellow = Fusobacteria, gray = others. Hospital day of death is indicated by black circles on the time line
Fig. 2
Fig. 2
Serial changes of the major five phyla in the patient group and control group. The serial compositions of Bacteroidetes and Firmicutes changed significantly more in the critically ill patients than in the control group (p = 0.014, 0.018, respectively). The serial compositions of Proteobacteria, Actinobacteria, and Fusobacteria were not statistically different
Fig. 3
Fig. 3
Serial changes in the ratio of Bacteroidetes to Firmicutes (B/F ratio) in the patient group and control group. A B/F ratio of >10 was seen in four of the six patients who died (black circles), whereas a B/F ratio of <0.10 was seen in only one of the six patient deaths. None of the survivors (triangles) had a B/F ratio >10 or >0.10 during the study period. There was a statistical difference in the B/F ratio between the dead patients and the survivors (p = 0.022)

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