Recent Insights into the Evolving Role of the Gut Microbiome in Critical Care

The data we have summarized all lead to the conclusion that disturbances in the gut microbiota sustained throughout critical illness-some of which are potentially modifiable-may contribute to injury that is independent of the primary cause of the patient's need for ICU care. However, clinical studies of microbiome-targeted interventions including the administration of prebiotic fiber and pro/synbiotics have failed to show consistent benefit in large RCTs or systematic meta-analyses, even despite strong signals indicating clinical benefit in individual studies. While these findings are at odds with numerous conditions faced in the outpatient setting where prebiotic/probiotic therapy have had readily demonstrable positive impacts (eg, autoimmune mediated diseases, cancer therapy, GI disorders, and COVID-19 pneumonia)(107,10)8 and it implies a knowledge gap that will require substantial future research both in the clinical and translational settings. We hypothesize that the absence of benefit observed in the current literature is due to a lack of specificity of treatment-all ICU patients at all times in their treatment course do not benefit from the currently available therapies, which may be poorly targeted to the type of dysbiosis seen in this setting. We propose that focus should be centered in several areas that are likely to be highly productive: 1. Understanding how to parse different types of ICU patients and different phases of their care as it relates to putatively harmful states of dysbiosis through both clinical and translational approaches; 2. Clarifying mechanisms under control of the HGM in the context of the ICU environment and identifying in which patients these mechanisms are clinically relevant; and 3. Designing therapies for the microbiome that are reflective of what is known about ICU-induced dysbiosis, taking into account the implications of disturbances in gut microbial ecological interactions, as well as gut barrier integrity. The types of microbiome-targeted interventions are rapidly increasing, and a better understanding of which therapies should be provided, and at what point in disease course, and to what population of patients has the potential for high impact in intensive care medicine.