Fig. 3: Enterobacteriaceae dysbiosis and impaired neutrophil host defense in critical illness.

a–d, NMDS ordinations (a,c) and comparisons of abundance (b,d) of adaptive immune cell (T and B cells) populations and innate immune cell populations (all neutrophils, monocytes, dendritic cells and innate lymphoid cell populations) (a,b) identified by clustering of mass cytometry data in the blood of ICU patients with (n = 18) or without (n = 26) progressive enrichment of Enterobacteriaceae in their fecal microbiota. Dots show individual patient-time points across the first 7 d of ICU admission, with statistical analysis by PERMANOVA accounting for repeated measures (a,c). e, t-SNE plots of neutrophils (left) and all other innate immune cells (right; monocytes, dendritic cells and NK cell clusters as indicated), with heat map overlay showing the log₂FC in abundance of each cell cluster between ICU patients with (n = 18) or without (n = 26) progressive enrichment of Enterobacteriaceae in their fecal microbiota. f, Correlation between fecal Enterobacteriaceae relative abundance and the quantity of mature (left) and immature (right) neutrophils (shown as proportion of total neutrophils) in ICU patients across the first week of admission analyzed using Spearman’s ranked correlation test. Dots show individual patient samples, regression (line) and 95% confidence intervals (shaded area) are shown. g, Comparison of neutrophil clusters in blood of ICU patients with (n = 18) or without (n = 26) Enterobacteriaceae enrichment (shown as log₂ fold difference of cluster abundance between groups). To determine the independent contribution of Enterobacteriaceae enrichment status (a–e,g), analyses controlled for clinical covariables that were independently associated with immune cell composition (Supplementary Table 15). i,j, Quantification of plasma NET markers (i) cell-free DNA and (j) MPO–DNA complexes on ICU day 3 in patients with (n = 18) or without (n = 26) Enterobacteriaceae enrichment. Dots represent individual patients, central line shows the median, box shows the IQR and whiskers show the range; statistical comparison was performed using a two-sided Mann–Whitney U-test. P values are shown.