Fig. 4
Dynamic variation of the vaginal microbiome across the different age groups. a Stack bar plot of the variation of average relative abundance of age-associated bacterial taxa across different age groups. The top 16 age-associated taxa determined by regression coefficient in MaAsLin are shown. The plot at the top denotes the average Shannon diversity of the age groups. b Relationships between age and the age-associated bacterial taxa. The Spearman correlations between the relative abundance of the top 16 age-associated taxa and age are shown as lines in the lower left region. The line width indicates the absolute value for the Spearman rho value. The line color indicates the direction of correlation (yellow for positive, gray for negative). The Pearson correlation between bacterial taxa is shown in the left plot. The size of the square in each cell is proportioned to the Pearson correlation r value. The dot plot at right indicates the mean relative abundance of taxa in women of different age groups (>45 vs. <=45). *, **, ***, **** indicate t-test P value < 0.05, 0.01, 0.001, 0.0001, respectively. c, d Microbiome networks of women in different age groups computed by sparCC. Analysis was conducted among 40 age-associated taxa determined by MaAslin. Nodes are colored according to the modules obtained from the maximal greedy algorithm within each network. The size of each node is proportional to the relative abundance of the taxa. Intra-module edges are colored by modules and inter-module edges are colored gray. The width of the lines reflects the strength of the correlations. e, f Degree of bacterial taxa of the microbiome network in different age groups. The taxa are ranked by the number of connections (i.e., degree). The horizontal dashed lines indicate the mean degree for bacterial taxa of the network in different age groups. g–i Sankey diagram showing the causal relationship of age-host variables-bacteria inferred by mediation analysis (ACME FDR < 0.05 & Total Effect FDR < 0.05 & Sensitivity Analysis rho > 0). Age-associated bacterial taxa and age-associated host variables were included in the mediation analysis. The beta coefficient and significance are labeled at the edge and the proportions of the mediation effect are labeled at the center. ***, FDR < 0.001
