Dysbiosis Of The Intestinal Microbiota In Neurocritically Ill Patients And The Risk For Subsequent Death

Background:During critical illness,the intestinal microbiota of patients is characterized by lower diversity,lower abundance of key commensal genera and in some cases dominated by a given genera,which is called intestinal microbiota dysbiosis.Microbiota dysbiosis can cause abnormal metabolism of short-chain fatty acids,resulting in impaired intestinal barrier or even poor prognosis.Microbiota-targeted therapy and prognostic value of microbiota characterization provide new treatment strategies of intensive care unit.However,little has been written about microbiome among neurocritically ill patients.Additional knowledge on the characteristics of the gut microbiota in neurocritically ill patients is required to provide preliminary data for microbiota intervention therapy in the future and better understand the clinical outcomes associated with microbial disturbances.Methods:This study has recruited 130 neurocritically ill adult patients admitted to the neurological intensive care unit,who have a length of stay more than 48 hours.Clinical parameters and severity scores were assessed at admission.Eighty four healthy subjects matched by age and gender served as controls.Fecal samples were collected at the time of admission(before antibiotics treatment)and every week after admission.The 16S rRNA gene sequencing was performed to monitor gut microbiome.The α diversity estimates the complexity within a community,and βdiverisity estimates differences between microbial communities.In addition,the concentration of fecal short-chain fatty acids was detected by gas chromatography-mass spectrometry.Results:a)The gut microbiota of neurociritally ill patients were significantly different from that of healthy controls as shown by β diversity.α diversity of neurocritically ill patients was significantly decreased compared to healthy controls.Lactobacillacea,Rikenellaceae,Verrucomicrobiaceae,Enterococcaceae,Porphyromonadaceae,Enterobacteriaceae were significantly enriched in NCU patients.Concentration of fecal acetate,propionate,butyrate and valerate were decreased in patients group.The multivariate Cox proportional hazard regression model showed that acetate,Betaproteobacteria,Burkholderiales,Alcaligenaceae,Faecalibacterium,and Sutterella were respectively associated with 90-day mortality.b)Spearman correlation analysis showed a significant negative correlation between Bacteroides and procalcitonin,and a significant positive correlation between Enterococcus and procalcitonin.There was a significant positive correlation between Bacteroides and acetate,propionate and butyrate.c)The α diversity was negatively correlated with sample time,and the distance from healthy controls estimated by βdiversity was positively correlated with sample time.The abundance of beneficial bacteria was significantly decreased over time in patients followed longitudinally,but the abundance of pathogens was increased.d)Subgroup analysis showed that 74 patients with cerebrovascular disease was significantly different from 74 age-and sex-matched healthy subjects as estimated by β diversity,and the a diversity of the patients group was significantly decreased.The acetate and butyrate in patients with cerebrovascular disease were significantly lower than the healthy control group.The multivariate Cox proportional hazards regression model showed four short-chain fatty acids(acetate,isobutyrate,isovalerate,and valerate)and abundance of three taxa(Barnesiellaceae,Christensenellaceae,and Faecalibacterium)were respectively associated with 90-day mortality.Conclusions:This analysis of gut microbiome from neurocritical ill patients indicates that the composition of the gut microbiome and fecal short-chain fatty acids differ significantly from that of a healthy population and the high abundance of specific taxa or high concentration of fecal short-chain fatty acids at admission were associated with risk for death.This research shed light on the new approach identifying high-risk patients in the future using microbiome sequencing or short-chain fatty acids detection.