Association Between Gut Dysbiosis and Sepsis-Induced Myocardial Dysfunction in Patients With Sepsis or Septic Shock

Chen, Yu; Zhang, Fu; Ye, Xin; Hu, Jianping; Yang, Xiao; Ye, Lin; Zhao, Bing-Cheng; Deng, Fan; Liu, Ke-Xuan

doi:10.3389/fcimb.2022.857035

Cited by 16 publications

(11 citation statements)

References 49 publications

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“…Compared to non-SIC patients, SIC patients showed higher SOFA and APACHE II scores, as well as higher levels of CK-MB, BNP, TnI, lactate, and PCT. This conclusion was consistent with those presented in earlier studies [48][49][50][51][52]. RAAS was stimulated and the Ang II levels are elevated during the initial sepsis stages [53].…”

Section: Discussionsupporting

confidence: 93%

Angiotensin-(1–7) ameliorates sepsis-induced cardiomyopathy by alleviating inflammatory response and mitochondrial damage through the NF-κB and MAPK pathways

et al. 2023

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Background There is no available viable treatment for Sepsis-Induced Cardiomyopathy (SIC), a common sepsis complication with a higher fatality risk. The septic patients showed an abnormal activation of the renin angiotensin (Ang) aldosterone system (RAAS). However, it is not known how the Ang II and Ang-(1–7) affect SIC. Methods Peripheral plasma was collected from the Healthy Control (HC) and septic patients and Ang II and Ang-(1–7) protein concentrations were measured. The in vitro and in vivo models of SIC were developed using Lipopolysaccharide (LPS) to preliminarily explore the relationship between the SIC state, Ang II, and Ang-(1–7) levels, along with the protective function of exogenous Ang-(1–7) on SIC. Results Peripheral plasma Ang II and the Ang II/Ang-(1–7) levels in SIC-affected patients were elevated compared to the levels in HC and non-SIC patients, however, the HC showed higher Ang-(1–7) levels. Furthermore, peripheral plasma Ang II, Ang II/Ang-(1–7), and Ang-(1–7) levels in SIC patients were significantly correlated with the degree of myocardial injury. Additionally, exogenous Ang-(1–7) can attenuate inflammatory response, reduce oxidative stress, maintain mitochondrial dynamics homeostasis, and alleviate mitochondrial structural and functional damage by inhibiting nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, thus alleviating SIC. Conclusions Plasma Ang-(1–7), Ang II, and Ang II/Ang-(1–7) levels were regarded as significant SIC biomarkers. In SIC, therapeutic targeting of RAAS, for example with Ang-(1–7), may exert protective roles against myocardial damage.

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Section: Discussionsupporting

confidence: 93%

Angiotensin-(1–7) ameliorates sepsis-induced cardiomyopathy by alleviating inflammatory response and mitochondrial damage through the NF-κB and MAPK pathways

et al. 2023

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“…The proportion of Actinobacteria was signi cantly reduced in patients with septic cardiomyopathy compared to those with non-septic cardiomyopathy. In contrast, a previous study by Chen Y et al [37] showed that patients with septic cardiomyopathy were characterized by an increase in Proteobacteria and a decrease in Bacteroidota at the portal level, which is inconsistent with our ndings. Combining multiple relevant factors that affect the gut microbiota [38] , including geography, diet, nutritional support, and antibiotic use, I must interpret our ndings cautiously here.…”

Section: Discussioncontrasting

confidence: 99%

Clinical study on the relationship between gut microbiota dysbiosis and iron metabolism and septic cardiomyopathy

Wang

Lin

et al. 2023

Preprint

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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.

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“…A number of preclinical experiments and clinical studies have reported the association between gut microbiota and sepsis. 10,[33][34][35][36][37][38][39] Several preclinical models have shown that disruption of the microbiota with antibiotics, paradoxically, increases the risk of bloodstream infections and critical illness. 11,12 This potential association has additionally been confirmed in the US Health and Retirement Study, in which a strong and consistent longitudinal dose-response relationship between suggested dysbiosis and progression to sepsis.…”

Section: Discussionmentioning

confidence: 99%

Causal associations between gut microbiota and sepsis: A two‐sample Mendelian randomization study

You

Zhang

et al. 2023

Eur J Clin Investigation

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BackgroundTargeting the gut microbiota may become a new therapeutic to prevent and treat sepsis. Nonetheless, the causal relationship between specific intestinal flora and sepsis is still unclear.MethodsA two‐sample Mendelian randomization study was performed using the summary statistics of gut microbiota from the largest available genome‐wide association study (n = 18,340). The summary statistics of sepsis were obtained from the UK Biobank (n = 486,484). Inverse‐variance weighted, weighted median and MR‐Egger were used to examine the causal association between gut microbiota and sepsis. Cochrane's Q test, MR‐Egger intercept test, MR‐PRESSO Global test and Rucker's Q'‐test were used for sensitivity analyses. The leave‐one method was used for testing the stability of MR results, and Bonferroni‐corrected was used to test the strength of the causal relationship between exposure and outcome.ResultsNine intestinal microflora were found causally associated with sepsis, and 11 intestinal microflora were causally associated with 28‐day death in sepsis. Among them, Order Victivallales had a strong causality with lower risk of sepsis (OR = 0.86, 95% CI: 0.78–0.94, p = .00165) and lower 28‐day mortality of sepsis (OR = 0.68, 95% CI: 0.53–0.87, p = .00179) after Bonferroni‐corrected test. No pleiotropy was detected.ConclusionsThrough the two‐sample MR analysis, we identified the specific intestinal flora that had a causal relationship with the risk and prognosis of sepsis at the level of gene prediction, which may provide helpful biomarkers for early disease diagnosis and potential therapeutic targets for sepsis.

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Association Between Gut Dysbiosis and Sepsis-Induced Myocardial Dysfunction in Patients With Sepsis or Septic Shock

Cited by 16 publications

References 49 publications

Angiotensin-(1–7) ameliorates sepsis-induced cardiomyopathy by alleviating inflammatory response and mitochondrial damage through the NF-κB and MAPK pathways

Angiotensin-(1–7) ameliorates sepsis-induced cardiomyopathy by alleviating inflammatory response and mitochondrial damage through the NF-κB and MAPK pathways

Clinical study on the relationship between gut microbiota dysbiosis and iron metabolism and septic cardiomyopathy

Causal associations between gut microbiota and sepsis: A two‐sample Mendelian randomization study

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