Clinical Study On The Relationship Between Gut Microbiota Dysbiosis And Iron Metabolism And Septic Cardiomyopathy

Background: Septic cardiomyopathy is a common complication of sepsis and is characterized by ventricular systolic and/or diastolic dysfunction and reduced ejection fraction.It was found that septic cardiomyopathy seriously affects the prognosis of patients with sepsis,so early diagnosis and intervention of septic cardiomyopathy is of great value to improve the prognosis of patients with sepsis.Studies have demonstrated the role of gut microbiota and iron metabolism in sepsis and cardiovascular disease,but few studies have reported on the changes and role of gut microbiota and iron metabolism in septic cardiomyopathy.The aim of this study was to explore the changes and correlation of gut microbiota and iron metabolism in septic cardiomyopathy and to provide new directions for early diagnosis of septic cardiomyopathy.Methods;This study was a single-center observational study.Patients with sepsis who were admitted to the critical care medicine department of Subei People’s Hospital between February 2022 and September 2022 were selected.Echocardiography was performed within 72 hours of the patient’s admission to the Intensive care unit.Patients were divided into septic cardiomyopathy group and non-septic cardiomyopathy group according to the grouping criteria.Blood and stool specimens were collected from patients included in the study on days 1,3 and 7 of enrollment.The blood specimens for testing of iron metabolism levels.The stool specimens were for 16 S rDNA sequencing to detect intestinal microbiota diversity.Clinical data were collected from both groups of patients,including basic information such as age,gender,Body Mass Index(BMI),Sequential Organ Failure Assessment(SOFA)and Acute Physiology and Chronic Health Evaluation II(APACHE II).To compare the gut microbiota diversity,iron metabolism level,28-day morbidity and mortality rate,length of ICU stay,and total length of stay in the two groups.Results: A total of 48 patients were enrolled during the study period,including 23 patients in the septic cardiomyopathy group and 25 patients in the non-septic cardiomyopathy group.Comparison of baseline characteristics between the two groups showed that there was no statistical significance(P > 0.05)for age,SOFA score,APACHE II score,Calcitonin I(cTnI),B-type natriuretic peptide(BNP),calcitoninogen(PCT),and interleukin-6(IL-6)in the two groups.However,there were statistical differences(P < 0.05)in the percentage of central venous pressure(CVP),and lactate(Lac)levels between the two groups,and all were higher in the septic cardiomyopathy group than in the non-septic cardiomyopathy group.Analysis of iron metabolism levels in the two groups showed that there was a statistical difference in serum ferritin(SF)levels between the two groups on day 1 and day 3 of enrollment(P < 0.05),and that ferritin levels were higher in the septic cardiomyopathy group than in the non-septic cardiomyopathy group.Other iron metabolism levels including serum iron(SF),serum transferring(TRF),transferrin saturation(TSAT),and total iron binding capacity(TIBC)on days 1,3,and 7 were not statistically significant(P > 0.05).Analysis of the richness and diversity of the gut microbiota in the two groups showed that the ACE index and Chao1 index were statistically different between the two groups(P < 0.01),while the Shannon index and Simpson index were not statistically different(P > 0.05).We further assessed time-related changes in gut microbiota alpha diversity in both groups and found a statistically significant decrease in Simpson’s index on day 7 compared to day 1 in the septic cardiomyopathy group(P < 0.05).Beta diversity of gut microbiota was analyzed in both groups and PCo A analysis showed a significant difference(P < 0.01).We compared the composition of the gut microbiota at different taxonomic levels in the two groups of patients,and at the portal level,the abundance of Actinobacteria(P=0.018)and unidentified＿Bacteria(P=0.024)was lower in the septic cardiomyopathy group.At the family level,the abundance of Aeromonadaceae was lower in the septic cardiomyopathy group(P=0.023).At the genus level,Citrobacter was more abundant in septic cardiomyopathy(P=0.007).At the species level,Bacteroides＿nordii(P=0.037)and[Clostridium]＿celerecrescens(P=0.026)were more abundant in septic cardiomyopathy.By Linear discriminant analysis Effect size(LEf Se)analysis,we identified Enterobacter and Klebsiella＿quasipneumoniae as possible gut microbe specific for septic cardiomyopathy(LDA score=4.2747,P=0.003).Using Spearman’s rank correlation analysis of clinical indicators and gut microbiota,we found that Bacteroides＿thetaiotaomicron was positively correlated with B-type natriuretic peptide(BNP),serum iron(SI),and transferrin saturation(TSAT)(P < 0.05).bacteroides＿fragilis was negatively correlated with calcitonin I(cTnI),transferrin(TRF),total iron binding capacity(TIBC)were negatively correlated(P < 0.05).prevotella＿disiens and prevotella＿timonensis were negatively correlated with ferritin(SF)(P < 0.05).The secondary observations of this study,including the patients’ 28-day morbidity and mortality rate,length of ICU stay,total length of stay,mechanical ventilation rate,continuous renal replacement therapy utilization rate,intensity of vasoactive drug use,and 24-hour fluid use in the enrolled group were not statistically different.Conclusion: Our study suggests that ferritin may have predictive value for early identification of septic cardiomyopathy,while Enterobacteriaceae may be the gut microbiota specific to septic cardiomyopathy.Furthermore,alterations in gut microbiota diversity may influence changes in iron metabolism and ultimately induce the development of septic cardiomyopathy,and larger studies are needed to validate this in the future.