Fig. 4

Summary of untargeted metabolomics from fasting plasma. a Distribution of the median participant-wise log₂-ratios of each metabolite. Color palette by study arm is reused in the remaining panels. b QQ-plot [40] with 1-percentile steps for each probiotic intervention arm versus placebo. Color shading as in (a). c Principal Component Analysis (PCA [41]) on the participant-wise log₂-ratios of each metabolite’s untargeted value. Each point represents a participant, with color shading by arm as in panel (A). Metabolites with low detection prevalence across the cohort were excluded (1156 of 1340 metabolites included). d Volcano-plot [42] summarizing the between-group multiple testing (Wilcoxon Rank Sum [37], two-sample, two-sided) of the participant-wise log₂-ratio of each metabolite. Vertical axis indicates the nominal p-value of each metabolite, while the horizontal axis indicates the estimated effect, structured as the Placebo group subtracted from the Formulation group (either WBF-011 or WBF-010). The full volcano scatterplot is repeated as light gray points in separate panels that have an additional layer of green- or blue-shaded points, with each panel emphasizing a different metabolite group of prior interest and apparent coordinated change. e Summary of the within-group changes (participant-wise log₂-ratios) for each study arm by metabolite and metabolite group highlighted in (d). Diamond and linerange indicates the group median and Wilcoxon 95% confidence interval, respectively