Gut Microbiome and Metabolome Were Altered and Strongly Associated With Platelet Count in Adult Patients With Primary Immune Thrombocytopenia

Figures

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  FIGURE 1. Alterations of gut microbiota in patients with primary immune thrombocytopenia (ITP) vs healthy controls (HCs). (A) Box plot of the Chao1 index, Shannon index and a two-dimensional plot of principal co-ordinates analysis built based on a bray matrix of the two groups. (B) Bacterial order, family, and genera enriched in feces of ITP patients. (C) Species enriched in ITP patients. (D) Phylum, genera and species depleted in ITP patients. The boxes represent the interquartile range, from the first and third quartiles, and the median is shown as a thick line in the middle of the box. The circles represent outliers beyond the whiskers. Each point in the graph represents a sample, and a color indicates a group of samples. pajust < 0.05 for all data selected.

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  FIGURE 2. Score plots using UPLC/MS data of fecal metabolites. (A) OPLS-DA score plots from metabolite profiles of ITP and HC samples. (B) A 200 times permutation test of OPLS-DA model. (C) Heat maps of the significantly differential metabolites between different samples. Each sample is visualized in a single column and each metabolite is represented by a single row. Green colors indicate lower metabolite concentration while red colors show enhanced metabolite levels (see color scale). (D) Differential metabolites between HC and ITP samples with VIP values greater than 3.0.

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  FIGURE 3. Prediction of ITP-enriched bacteria and metabolites. (A) Receiver-operating characteristic (ROC) plot for Streptococcus, Streptococcus anginosus and Streptococcus salivarius, areas under the parametric curve (AUC) value are 0.875, 0.880, and 0.856, respectively. (B) ROC plot for Cer (t18:0/16:0), Cer (d18:1/17:0), and PI [20:1(11Z)/22:4(7Z,10Z,13Z,16Z)], AUC are 0.861, 0.874, and 0.850, respectively. (C,D) The ROC analysis of the combination of Weissella and Streptococcus anginosus, or Cer (t18:0/16:0), Cer (d18:1/17:0), and 13-hydroxyoctadecanoic acid, with their corresponding AUC reaching 0.948 and 0.984, respectively.

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  FIGURE 4. Associations between altered gut microbiome, metabolites, and hematological variables in ITP. (A) Association of ITP-altered fecal bacteria, metabolites with hematological variables. (B) The association of ITP-altered fecal bacteria with metabolites. Correlation coefficients (in absolute value) higher than 0.4 and p < 0.0001 were used as significance thresholds. (C) The association of ITP-altered gut microbiota and metabolites and platelet count. The pink color, light green, and orange represent bacteria, metabolites, and platelet count, respectively. Blue line represents negative correlation, while red line represents positive correlation.

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  FIGURE 5. Functional analysis of predicted metagenomes. (A) PICRUSt results of downregulated metabolic pathways in the gut microbiome of ITP patients. (B) Top 10 enriched metabolic pathways between the HC and ITP groups. (C) PICRUSt results of elevated metabolic pathways in the gut microbiome of ITP patients.