The gastrointestinal microbiome in critical illness: A Clinician's guide to mechanisms, emerging tools, and therapeutic questions

There is considerable interest in the gastrointestinal (GI) microbiome and its interaction with disease processes, but existing reviews tend to assume ecological and microbiological knowledge that critical care clinicians may not have. In this review, we present an overview of the GI microbiome for the critical care clinician and highlight unanswered questions pertinent to the field. The human GI microbiome can now be mapped and its relationship with organ function interrogated. Multiomics approaches that integrate data from multiple sources, including the microbiome, epigenome, transcriptome, metabolome, and proteome, offer promise in unravelling the hitherto inconsistent results of interventions to modify the microbiome, with a view to improving outcomes. Resident microbes are implicated in local and systemic immune dysregulation during critical illness. While the mechanisms underlying relationships between the GI microbiome and organ function in health and disease remain incompletely understood, a byproduct of saccharolytic fermentation of dietary fibre in the colon, short-chain fatty acids (SCFAs), are a key modulator of these relationships. Pertinent to the use of prebiotic formulations in treating chronic disease and critical illness, are the comparatively unexplored bidirectional interactions between the microbiome and host. More observational and interventional data, using advanced laboratory techniques, are needed to understand if these are causal relationships.