Rethinking the causal framework in microbiome research

The field of microbiome research has fundamentally changed our perception of the host-microbe interaction in maintaining health and predisposing or causing disease. While the majority of the research so far has focused on identifying association rather than elucidating causal mechanisms, the field has evolved rapidly to address these shortcomings. One prominent effort in moving from correlation to causation lies in the adaptation of the Koch’s postulates to the microbiome. There is a growing need to revisit the Koch’s postulates in light of our better understanding of the role of human microbiome and association of microbial community features such as metabolic potential with diseases. Attempts have been made to either adapt Koch’s postulates to microbiome research (e.g., commensal Koch’s postulates and ecological Koch’s postulates) or to propose independent frameworks for causal microbiome research (e.g., perturb-to-predict paradigm or integrating ecological context into causal microbiome research).

While there are exciting advancements in the field of causal microbiome research, important shortcomings have been raised in the field. We believe that these shortcomings are three folds: 1) the complex and multifactorial causal architecture underlying many diseases, is often disregarded in causal microbiome studies; 2) the revised Koch’s postulates remain inadequate to provide a framework for causal microbiome research; 3) most attempts to provide a framework for reproducible causal microbiome research lacks input on pertienent philosophical aspects of causality including causal selection and complexity.

In collabortion with Dr Marie-Claire Arrieta, a leading microbiome scientist, and Dr Megan Delehanty who specialises in philosophy of science and medicine, we examine the assumptions of the existing causal microbiome frameworks and propose a new framework to establish causality in microbiome research.

Shirin Moossavi
Shirin Moossavi
Postdoctoral Fellow