Figure 3. Structural equation model describing the pattern of interrelationships between exposures, microbiome, and host inflammation. A modified path diagram of the final SEM supporting the mediatory effect of the gut microbiota on inflammation. The heatmaps represent direct associations of diet, behavior, and demographics with the gut microbiota and inflammatory biomarkers. Only significant paths of the effect of the gut microbiota on inflammation are shown. Standardized β coefficients are reported. Species Factors 1–6 denote latent variables of the community gut microbiota modeled as exploratory factor analysis (EFA) regression scores of the species relative abundance; Biomarker Factors 1–3 denote latent variables representing community inflammatory biomarkers as grouped using EFA. *p 0.1–0.05, **p 0.05–0.001, ***p<0.001. Edge colors : Green: positive association; red: negative association. Black arrows indicate the direction of association of diet, demographics, and behavioral exposures with both inflammatory biomarkers and the gut microbiota. Figure 3—figure supplement 1. Theoretical models for assessing the structure of associations between the various human exposures, the gut microbiota, and the host’s inflammatory profile. (a) Final framework (framework 1): The gut microbiome mediates, in part, the relationship between exposure risk factors and host inflammation. (b) Framework 2: The gut microbiome and exposure risk factors both, independently, impact host inflammation. (c) Framework 3: Exposure risk factors are associated with gut microbiome and inflammatory profile, but there is no relationship between microbiome and inflammation. (d) Framework 4: Exposure risk factors are associated with the inflammatory profile, and the inflammatory profile predicts the gut microbiome composition.