Methodological strategies in microbiome research and their explanatory implications

Abstract

Early microbiome research found numerous associations between microbial community patterns and host physiological states. These findings hinted at community-level explanations. “Top-down” experiments, working with whole communities, strengthened these explanatory expectations. Now, “bottom-up” mechanism-seeking approaches are dissecting communities to focus on specific microbes carrying out particular biochemical activities (e.g., choline metabolism pathways, Clostridium difficile suppression). To understand the interplay between methodological and explanatory scales, we examine claims of “dysbiosis,” when host illness is proposed as the consequence of a community state. Our analysis concludes with general observations about how methodologies relate to explanations, and the implications for microbiome research.