Structural equation modelling the impact of antimicrobials on the human microbiome. Colonization resistance versus colonization susceptibility as case studies.

Abstract

The impact of antimicrobials on the human microbiome and its relationship to human health are of great interest. How antimicrobial exposure might drive change within specific constituents of the microbiome to effect clinically relevant endpoints is difficult to study. Clinical investigation of each step within a network of causation would be challenging if done ‘step-by-step’. An analytic tool of great potential to clinical microbiome research is structural equation modelling (SEM), which has a long history of applications to research questions arising within subject areas as diverse as psychology and econometrics. SEM enables postulated models based on a network of causation to be tested en bloc by confrontation with data derived from the literature. Case studies for the potential application of SEM techniques are colonization resistance (CR) and its counterpart, colonization susceptibility (CS), wherein specific microbes within the microbiome are postulated to either impede (CR) or facilitate (CS) invasive infection with pathogenic bacteria. These postulated networks have three causation steps: exposure to specific antimicrobials are key drivers, clinically relevant infection endpoints are the measurable observables and the activity of key microbiome constituents mediating CR or CS, which may be unobservable, appear as latent variables in the model. SEM methods have potential application towards evaluating the activity of specific antimicrobial agents within postulated networks of causation using clinically derived data.