Fig. 3: Gradual shifts in gut microbiome composition in response to ETI are driven by antibiotics and steroids, including Escherichia decline linked to reduced intestinal inflammation. | Nature Communications

Fig. 3: Gradual shifts in gut microbiome composition in response to ETI are driven by antibiotics and steroids, including Escherichia decline linked to reduced intestinal inflammation.

From: CFTR modulator therapy drives microbiome restructuring through improved host physiology in cystic fibrosis: the IMMProveCF phase IV trial

Fig. 3: Gradual shifts in gut microbiome composition in response to ETI are driven by antibiotics and steroids, including Escherichia decline linked to reduced intestinal inflammation.The alternative text for this image may have been generated using AI.

a Stool microbiome composition shifts from baseline (PERMANOVA on BC-dissimilarities, stratified by donor, adjusted for sex and age: Months from ETI start R2 = 2.3%, p = 0.001). PCoA shows first two dimensions; arrows connect each sample to its baseline. Colors indicate months from ETI treatment start: black=baseline (N = 34), yellow=3 months (N = 26), blue=6-12 months (N = 76), red=15-18 months (N = 40), green=21-24 months (N = 31). Geometric markers show mean shift from baseline. b Microbiome variance (R2) explained between sampling time points (PERMANOVA on BC-dissimilarities, stratified by donor). Circle size reflects R2; color indicates p-value, details in Supplementary Data 17. c Relative abundance of Escherichia-Shigella in stool samples across time and controls. Significance vs. baseline assessed by LME (ID as random factor). FDR < 0.1 (.), FDR < 0.05 (*), FDR < 0.01 (**), and FDR < 0.001 (***), values in Supplementary Data 7. Box plots show the median (line), IQR (box), 1.5× IQR range (whiskers), and outliers (points beyond whiskers). Sample time points are color-coded. d Microbiome variance (R2) explained by individual covariates. Blue: significant in simple, purple: in multiple PERMANOVA on BC-dissimilarities (p < 0.05), details in Supplementary Data 18. e Alpha diversity metrics (calculated on rarefied reads to minimum sequencing depth) significantly associated with clinical metadata. Heatmap hues represent signed effect sizes (Spearman’s rho or Cliff’s delta). FDR < 0.1 (.), FDR < 0.05 (*), FDR < 0.01 (**), and FDR < 0.001 (***). Features shown have effect size > |0.2 | . Details in Supplementary Data 8. f Fecal calprotectin negatively correlates with Escherichia-Shigella abundance. Sample time points are color-coded. Effect size= 0.31, FDR = 0.04, without confounders reported by metadeconfoundR. line =linear fit; shaded areas = 95% confidence intervals. g CFTR modulators inhibit growth of several gut microbes in vitro. Antibiotics were tested as controls. IC₂₅ = concentration for 25% growth inhibition after 22 h drug exposure compared to growth in 1% DMSO (i.e., untreated control). “<“ = IC25 below tested; “>“ = IC25 above tested dose.

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