A Study Of The Effect Of Enteral Nutrition And Its Related Adverse Events On Intestinal Microbiome Disturbance In Ischemic Stroke

Background:Dysbiosis,deterioration of the barrier function of the intestinal epithelium,decreased immune function and translocation of intestinal microbiome are widespread in cerebral infarction.Conversely,intestinal bacterial disorders exacerbate the dysbiosis host response,creating a vicious cycle that leads to poor prognosis.A series of prognosis-related adverse reactions can accompany enteral nutrition therapy,including hyperglycemia,refeeding syndrome,and gastrointestinal intolerance.Exploring the relationship between adverse reactions and intestinal microbiome is beneficial to clarify the advantages and disadvantages of enteral nutrition in clinical work and provide a basis for future targeted microbiome intervention therapy.Methods:A total of 146 patients with cerebral infarction receiving enteral nutrition therapy who were admitted to the neurology department were included in this study,divided into a study cohort of 80 patients and a dynamic cohort of 66 patients.An additional 54 patients who were fed by mouth and 17 healthy people were included as controls.All patients had stool and blood specimens continuously retained at 5-7 day intervals after admission to the hospital.Stool specimens were sequenced using 16S rRNA.LefSe analysis was performed to find specific differential bacteria α and βspecies diversity was used to indicate group community structure differences;meanwhile,enzyme-linked immunosorbent assay was used to detect intestinal microecological indicators levels within blood samples.Results:①Compared to the HC(Health Control)and ON(Oral Nutrition)groups,patients receiving enteral nutrition exhibited a significantly different gut microbiota composition in admission,including decreased alpha diversity,enrichment of opportunistic pathogenic Enterococcus and a decrease in beneficial bacteria such as Lachnospiraceae and Braunschweiger.②The degree of intestinal flora disturbance in patients during nutrition was further aggravated by a continuous decrease in alpha species diversity.③In the correlation analysis,the taxa Bacteroidetes was significantly and negatively correlated with SOFA(Sequential Organ Failure Assessment)score.Actinobacteria and Bifidobacterium were significantly and negatively correlated with liver enzymes and creatinine.CRP(C Reactive Protein)was significantly and negatively correlated with the phylum Archaea,Zurichiaceae,Firmicutes and Clostridium.④The incidence of enteral nutrition-related adverse events hyperglycemia,refeeding syndrome,and gastrointestinal intolerance in stroke patients was 16.4%,23.6%,and 35.6%,respectively.The risk of death in stroke patients with enteral nutrition-associated hyperglycemia was significantly higher,and there was a trend toward higher risk of distant death from refeeding syndrome and gastrointestinal intolerance,but there was no statistically significant difference.⑤Compared to the well-tolerated population,patients with enteral nutrition-related adverse events already have dysbiosis in admission.⑥Adverse event-related flora differences were all further exacerbated during hospitalization.Patients with hyperglycemia occurred with a similar trend of flora disorders as diabetic patients,all out of decreased alpha diversity during nutrition and reduced abundance of beneficial bacteria such as bifidobacteria and short-chain fatty acid-producing bacteria.Conclusions:In this study,enteral nutrition and its associated adverse events were found to be associated with intestinal flora disturbance in patients with cerebral infarction,with the degree of disturbance further exacerbated during nutrition.This study provides a new basis for the treatment of intestinal flora disturbance during enteral nutrition and suggests that the use of intestinal flora sequencing may be a potential tool to identify the occurrence of adverse events in enteral nutrition in future.