Association between gut microbiome profiles and host metabolic health across the life course: a population-based study

Figures

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  Fig. 1. A schematic figure of analyses performed in this study. Each frame shows the performed analysis (in black) and correspondent analysis approach (in white); cohorts that were used for performing each of the analyses are also shown (in red) besides the analysis. Microbiome-pattern clustering was performed at the ASV level, while all other association analyses were performed at the genus level.

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  Fig. 2. Visualization of two clusters in the background of the ASV's principal component analysis within each cohort (a) the Generation R Study, (b) the Rotterdam Study, and (c) the Lifelines-DEEP Study. Visualization of the first two principal components derived from the corresponding ASV tables. Coloring on the figures corresponds to the cluster assignment by the K-means algorithm. For each cohort, the results of the average silhouette width algorithm to select the optimal number of clusters are shown in the right panels.

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  Fig. 3. Top genera contributing to cluster assignment. Top 10 genera contributing to cluster assignment within (a) the Rotterdam Study, (b) the Generation R Study, and (c) the Lifelines-DEEP Study. The prevalence of each genus is reported as a percentage on the corresponding study population. Bars represent the log fold change (LFC) of cluster U with respect to cluster H. Red bars represent genera with a higher abundance in cluster U, whereas cyan bars represent genera with a lower abundance in cluster U.

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  Fig. 4. Overlapped differentially abundant genera across the three cohorts. Bars represent log-fold change in genera abundance for cluster U (cluster H used as reference). Red bars refer to the Generation R Study, green bars refer to the Lifelines-DEEP Study, and blue bars refer to the Rotterdam Study. “LFC.clusterU”, Log-fold change for cluster U compared to cluster H.

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  Fig. 5. Forest plot visualizing independent risk factors associated with an unhealthy microbiome cluster derived from logistic regression model for each cohort. The black diamond in the middle of the purple line represents the effect size of the association, and the purple line represents the 95% confidence interval. Within each column, no data indicates the corresponding variable is either missing in the final model or not significant. “∗” the reported OR (95%) CI corresponds to low education level, as medium level was used as reference for LLD. GenR, Generation R Study; RS, Rotterdam Study, and LLD, Lifelines-DEEP Study.

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  Fig. 6. Kaplan Meier curves of incidence-free atherosclerotic cardiovascular disease (ASCVD) by microbiome cluster in the Rotterdam study. The x-axis denotes follow-up time in months, and the y-axis denotes the proportion of individuals who did not get incident ASCVD at each of the follow-up time points. The number of individuals who were at risk of ASCVD at each time point is presented in the lower panel. The green curve represents individuals from microbiome cluster H, and the yellow one represents individuals from microbiome cluster U.