Lower gut dysbiosis and mortality in acute critical illness: a systematic review and meta-analysis

Abstract

Background The human gastrointestinal tract harbours a complex multi-kingdom community known as the microb\iome. Dysbiosis refers to its disruption and is reportedly extreme in acute critical illness, yet its clinical implications are unresolved. The review systematically evaluates the relationship between gut dysbiosis and clinical outcomes of patients early in critical illness. Methods Following PRISMA guidelines, a prospectively registered search was undertaken of MEDLINE and Cochrane databases for observational studies undertaking metagenomic sequencing of the lower gastrointestinal tract of critically ill adults and children within 72hours of admission. Eligible studies reported an alpha diversity metric and one or more of the primary outcome, all cause mortality, or secondary clinical outcomes. After aggregate data was requested, meta-analysis was performed for 4 studies with mortality stratified to high or low Shannon index. Results The search identified 26 studies for systematic review and 4 had suitable data for meta-analysis. No effect of alpha diversity was seen on mortality after binary transformation of Shannon index (odds ratio 0.52, CI 0.12–4.98, I2 = 0.64) however certainty of evidence is low. Pathogen dominance and commensal depletion were each more frequently associated with mortality, adverse clinical and ecological sequalae, particularly overabundance of Enterococcus. Conclusions There is a paucity of large, rigorous observational studies in this population. Globally, alpha diversity was dynamically reduced in early ICU admission and was not associated with in-hospital mortality. The abundance of taxa such as Enterococcus spp. appear to offer greater predictive capacity for important clinical and ecological outcomes.