Dysbiosis of the intestinal microbiota in neurocritically ill patients and the risk for death

Abstract

Background: Despite the essential functions of the intestinal microbiota in human physiology, little has been reported about the microbiome in neurocritically ill patients. This investigation aimed to evaluate the characteristics of the gut microbiome in neurocritically ill patients and its changes after admission. Furthermore, we investigated whether the characteristics of the gut microbiome at admission were a risk factor for death within 180 days.

Methods: This prospective observational cohort study included neurocritically ill patients admitted to the neurological intensive care unit of a large university-affiliated academic hospital in Guangzhou. Faecal samples were collected within 72 h after admission (before antibiotic treatment) and serially each week. Healthy volunteers were recruited from a community in Guangzhou. The gut microbiome was monitored via 16S rRNA gene sequence analysis, and the associations with the clinical outcome were evaluated by a Cox proportional hazards model.

Results: In total, 98 patients and 84 age- and sex-matched healthy subjects were included in the analysis. Compared with healthy subjects, the neurocritically ill patients exhibited significantly different compositions of intestinal microbiota. During hospitalization, the α-diversity and abundance of Ruminococcaceae and Lachnospiraceae decreased significantly over time in patients followed longitudinally. The abundance of Enterobacteriaceae was positively associated with the modified Rankin Scale at discharge. In the multivariate Cox regression analysis, Christensenellaceae and Erysipelotrichaceae were associated with an increased risk of death. The increases in intestinal Enterobacteriales and Enterobacteriaceae during the first week in the neurological intensive care unit were associated with increases of 92% in the risk of 180-day mortality after adjustments.

Conclusions: This analysis of the gut microbiome in 98 neurocritically ill patients indicates that the gut microbiota composition in these patients differs significantly from that in a healthy population and that the magnitude of this dysbiosis increases during hospitalization in a neurological intensive care unit. The gut microbiota characteristics seem to have an impact on patients' 180-day mortality. Gut microbiota analysis could hopefully predict outcome in the future.

Keywords: Biomarker; Cohort study; Critical illness; Dysbiosis; Gut microbiome; Prognosis; Stroke.

Fig. 1

Flow diagram of the patient selection process

Fig. 2

Area plot of the intestinal microbiota abundance of the first sample in each individual. The intestinal microbiota abundance was compared between neuroICU patients (P1, P2, …, P98) and HCs (C1, C2, …, C33) at phylum (a) and family (b) levels. neuroICU neurological intensive care unit, HCs healthy controls

Fig. 3

Dynamic changes in the intestinal microbiota of neuroICU patients. a PCoA plot illustrating the grouping patterns of the samples collected at admission and discharge. The “+” represents the mean and SD of the group. The distances between every “+” represent the dissimilarities between these two groups. b The diversity of the microbiota, presented as the Shannon index, was calculated from 50 paired samples collected within 72 h at admission and at discharge. ***, p < 0.001. c, d Temporal changes in the Shannon index (c) and PD–whole tree index (d) of the neuroICU group followed longitudinally every week during neuroICU hospitalization. e, f Temporal changes in the Bray–Curtis distance (e) and unweighted UniFrac distance (f) of the neuroICU group followed longitudinally every week during neuroICU hospitalization. PCoA principal coordinate analysis, SD standard deviation, PD phylogenetic diversity, neuroICU neurological intensive care unit

Fig. 4

Dynamic changes in specific taxa during neuroICU hospitalization. Bacteroidetes (a) and Proteobacteria (c) were not correlated with the length of hospital stay. Firmicutes (b) was negatively associated with the sample collection time. Ruminococcaceae (d) and Lachnospiraceae (e) were significantly correlated with length of stay. Enterobacteriaceae (f) was not associated with the sample collection time