Gut bacteriobiota and mycobiota are both associated with Day-28 mortality among critically ill patients

Abstract

Introduction Gut microbiota is associated with host characteristics such as age, sex, immune condition or frailty and is thought to be a key player in numerous human diseases. Nevertheless, its association with outcome in critically ill patients has been poorly investigated. The aim of this study is to assess the association between gut microbiota composition and Day-28 mortality in critically ill patients. Methods Rectal swab at admission of every patient admitted to intensive care unit (ICU) between October and November 2019 was frozen at − 80 °C. DNA extraction was performed thanks to QIAamp® PowerFecal® Pro DNA kit (QIAgen®). V3–V4 regions of 16SRNA and ITS2 coding genes were amplified by PCR. Sequencing (2x250 bp paired-end) was performed on MiSeq sequencer (Illumina®). DADA2 pipeline on R software was used for bioinformatics analyses. Risk factors for Day-28 mortality were investigated by logistic regression. Results Fifty-seven patients were consecutively admitted to ICU of whom 13/57 (23%) deceased and 44/57 (77%) survived. Bacteriobiota α-diversity was lower among non-survivors than survivors (Shannon and Simpson index respectively, p < 0.001 and p = 0.001) as was mycobiota α-diversity (respectively p = 0.03 and p = 0.03). Both gut bacteriobiota and mycobiota Shannon index were independently associated with Day-28 mortality in multivariate analysis (respectively OR: 0.19, 97.5 CI [0.04–0.60], p < 0.01 and OR: 0.29, 97.5 CI [0.09–0.75], p = 0.02). Bacteriobiota β-diversity was significantly different between survivors and non-survivors (p = 0.05) but not mycobiota β-diversity (p = 0.57). Non-survivors had a higher abundance of Staphylococcus haemolyticus, Clostridiales sp., Campylobacter ureolyticus, Akkermansia sp., Malassezia sympodialis, Malassezia dermatis and Saccharomyces cerevisiae, whereas survivors had a higher abundance of Collinsella aerofaciens, Blautia sp., Streptococcus sp., Faecalibacterium prausnitzii and Bifidobacterium sp. Conclusion The gut bacteriobiota and mycobiota α diversities are independently associated with Day-28 mortality in critically ill patients. The causal nature of this interference and, if so, the underlying mechanisms should be further investigated to assess if gut microbiota modulation could be a future therapeutic approach.

Oropharyngeal and intestinal concentrations of opportunistic pathogens are independently associated with death of SARS-CoV-2 critically ill adults

“…More recently, the presence of Enterobacterales in rectal samples or the dominance of Enterococcus in patients at admission to the intensive care unit has been associated with a higher risk of death [ 8 , 9 ]. Recently, the composition of the microbiota was associated with mortality at D28 in patients hospitalized in intensive care unit (ICU), with a lower diversity being associated with death [ 10 ]. Beyond colonization, we showed that the oropharyngeal and rectal concentrations of extended-spectrum beta-lactamase (ESBL)—producing Enterobacterales —could be a powerful tool to estimate the risk of subsequent ventilator-associated pneumonia (VAP) caused by ESBL-producing Enterobacterales in mechanically ventilated patients [ 11 ].…”

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

“…The only singular commensal taxon to predict survival, Wei et al (19), showed depletion of Bi dobacterium was associated ICU mortality (p = 0.031) and improved performance of APACHEII and SOFA scores in multivariate models. Together with other groups -Blautia (various species) Faecalibacterium, Collinsella and Streptococcus -Bi dobacterium abundance was associated with survival in one other study (22).…”

“…There were 26 studies eligible for systematic review of which 7 provided moderate certainty evidence (15)(16)(17)(18)(19)(20)(21). Alpha diversity was signi cantly predictive of mortality in only one (22). In contrast, pathogen dominance (6 studies) and commensal loss (2 studies) appear to be more highly predictive of mortality among other adverse outcomes.…”

“…One study of 26 reported a lower shannon index in non-survivors compared with survivors (22). Aardema et al (21) noted low alpha diversity (Shannon index < 3) was overrepresented in patients who suffered hospital complications but this did not reach signi cance and no mortality relationship was seen.…”

Is compromised intestinal barrier integrity responsible for the poor prognosis in critically ill patients with pre-existing hyperglycemia?

“…As the main part of intestinal biological barrier, gut microbiota is significant for the integrity and function of intestinal barrier, and yet the dysbiosis of gut microbiota, also known as gut dysbiosis, will impair the homeostatic balance of intestinal barrier integrity [6]. Clinical study has found that gut microbiota is associated with 28-day mortality among critically ill patients [22]. Given the interactions with various organs, the gut dysbiosis and compromised intestinal barrier integrity deeply participate in the development and exacerbation of critical illness [23][24][25].…”