Clinical study on the relationship between gut microbiota dysbiosis and iron metabolism and septic cardiomyopathy
Authors: Li Xianghui , Wang Jing , Song Lin , Zhang Mengfei , Yang Jiayan , Zheng  , Yu Jiangquan 
Published: June 2023

Abstract
Background: Septic cardiomyopathy is a common complication of sepsis and is characterized by ventricular systolic and/or diastolic dysfunction and reduced ejection fraction. 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, prospective, 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 16S rDNA sequencing to detect intestinal microbiota diversity. The basic vital signs and clinical data of the patient were recorded. 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. Analysis of iron metabolism levels in the two groups showed that there was a statistical difference in serum ferritin 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, serum transferring, transferrin saturation, and total iron binding capacity 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). Beta diversity of gut microbiota was analyzed in both groups and PCoA 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 phylum 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 (LEfSe) 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, serum iron, and transferrin saturation (P < 0.05). Bacteroides_fragilis was negatively correlated with cardiac Troponin I, transferrin, total iron binding capacity were negatively correlated (P < 0.05). Prevotella_disiens and Prevotella_timonensis were negatively correlated with ferritin (P < 0.05).
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.
Trial registration: The trial completed registration at the China Clinical Trials Registry (registration number ChiCTR2200056572) on 8 February 2022, and the study was conducted in strict accordance with the registration information.