Fig. 4: Sulfur metabolism links disease activity to human microbiome in humanized mice.

a PCA score plot of metabolite profiles of mice colonized with microbiota from human donors with active disease pre-HSCT (n = 10), active (n = 12) or inactive (n = 10) disease post-HSCT. b PLS-DA plot comparison of metabolite profiles of mice based on disease activity of their original human donors (active pre-and post-HSCT) and (inactive post-HSCT). c Volcano plot of 1252 differentially abundant metabolites selected based on fold change log 2 ≥ 3) and significance (p < 0.01). d Correlation plot of bile acid concentrations and disease activity. e LEfSe generated from PICRUSt2 identified the most differentially abundant functional modules between mice colonized with microbiota from human donors with active (n = 37) or inactive disease (n = 18). A number of 42 KEGG modules significantly enriched in mice colonized with microbiota from patients during active disease and 42 KEGG modules were enriched patients with inactive disease (significance: log10FC > 2 and p < 0.01.). Inactive (post-HSCT) functional modules are indicated with a positive LDA score (blue) and modules enriched in (active post-HSCT) with a negative score (red). Only functional modules meeting an LDA significant threshold of >2 are shown. f Cladogram obtained from LEfSe analysis of functional genes according to KEGG using shotgun metagenomics. g Cladogram plotted from LEfSe analysis showing the taxonomic levels represented by rings with phyla in the outermost the ring and genera in the innermost ring. Each circle is a member within that level. Those taxa in each level are colored by disease state of human donor for which it is more abundant (p < 0.05; LDA score 2). KEGG Kyoto Encyclopedia of Genes and Genomes, LEfSe linear discriminant analysis effect size, PICRUSt Phylogenetic Investigation of Communities Reconstruction of Unobserved State.