Oxygenation and intestinal perfusion and its association with perturbations of the early life gut microbiota composition of children with congenital heart disease

Figures

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  Figure 1. Description of cohort. Samples from 43 neonates were analyzed within this study. Groups were divided into healthy controls (HC) and neonates with congenital heart disease (CHD). Two other independent subgroups were created separately according to mode of delivery (HC and CHD) and according to oxygen saturation (SpO2) of ≤90% or > 90% (CHD group only).

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  Figure 2. (A–C) Relative abundance of 10 most frequent genera by group and mode of delivery. Relative abundance (0–1.0) of the 10 most frequent genera are shown according to group (A), mode of delivery (B) and the combination of group and mode of delivery (C). HC, healthy control; CHD, congenital heart disease.

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  Figure 3. Diversities of all genera by type of birth according to patient cohort (CHD or HC). Box-Whisker Plots with median and interquartile range (IQR) of alpha diversity metrics (Shannon’s, Simpson’s and InvSimpson indices) of the intestinal microbiota composition according to mode of delivery and divided by patient group (CHD, HC). All values are displayed on the same scale to allow for comparison of different constellations. p-values for comparison are not given due to small numbers and lack of inference toward a general population.

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  Figure 4. (A,B) Model of the effect of SpO2 on intestinal microbiota composition of congenital heart disease (CHD) patients under consideration of mode of delivery. Intestinal core microbiota composition data and oxygen saturation (SpO2) of neonates with CHD were used to create this visual, statistical model showing shifts in the intestinal core microbiota composition (y-axis: relative frequencies, 0–1.0) according to gradual alterations in SpO2 (%). Model for neonates with CHD born by vaginal delivery (A), neonates with CHD born by cesarean section (B) was assessed by MANOVA.

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  Figure 5. Hypothesis free cluster analysis of microbiota composition of patients with congenital heart disease (CHD). Heat map of relative abundances of the dominating genera in the total cohort of neonates with CHD (n = 13) in combination with the dendrogram resulting from an unsupervised hierarchical cluster analysis. Plotted genera were limited to those that resulted in a relative abundance of at least 0.1. The assignment of cases to final clusters followed essentially the results from the cluster analysis except case “P04.” This was reassigned to a different cluster due to its content of the genus Streptococcus. Patient numbers in italic are those born by cesarean section, others were born by vaginal delivery. Cluster 1 (red) was either dominated by the phylum Firmicutes and the genera Staphylococcus or Enteroccocus with low interindividual diversity. Cluster 2 (black) was mainly dominated by the phylum Proteobacteria, and the genera Pseudomonas, Escherichia, Klebsiella and Enterobacter, but showed high interindividual diversity. Cluster 3 (blue) consisted of 3 patients and was mainly characterized by a more diverse microbiota composition and presence of the genus Streptococcus in all…

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  Figure 6. (A–E) Boxplots of oxygen saturation and perfusion parameters according to the three identified different microbiota composition clusters. Box whisker plots for oxygen saturation (SpO2, %) (A), intestinal fractional tissue oxygen extraction (iFTOE, fraction) (B), relative blood flow velocity in the liver (rlVelocityAU) (C) and umbilical region (ruVelocityAU) (D), and global gut perfusion per birth weight (E) according to grouping by the three identified different microbiota composition clusters. Cluster 1 (red), Cluster 2 (black), Cluster 3 (blue). p-values result from Wilcoxon tests and applied oxygenation and perfusion parameters according to the three clusters. p-values here give rather the probability to see a more extreme result of the statistical test function within our sample subset than that actually proving the null hypothesis to be true. Thus, the result gives hardly any clue toward generalization.