Intestinal microbiota and metabolome perturbations in ischemic and idiopathic dilated cardiomyopathy.

BACKGROUND: Various clinical similarities are present in ischemic (ICM) and idiopathic dilated cardiomyopathy (IDCM), leading to ambiguity on some occasions. Previous studies have reported that intestinal microbiota appeared dysbiosis in ICM, whether implicating in the IDCM remains unclear. The aim of this study was to assess the alterations in intestinal microbiota and fecal metabolites in ICM and IDCM. METHODS: ICM (n = 20), IDCM (n = 22), and healthy controls (HC, n = 20) were enrolled in this study. Stool samples were collected for 16S rRNA gene sequencing and gas chromatography-mass spectrometry (GC-MS) analysis. RESULTS: Both ICM and IDCM exhibited reduced alpha diversity and altered microbial community structure compared to HC. At the genus level, nine taxa including Blautia, [Ruminococcus]_torques_group, Christensenellaceae_R-7_group, UCG-002, Corynebacterium, Oceanobacillus, Gracilibacillus, Klebsiella and Citrobacter was specific to ICM, whereas one taxa Alistipes uniquely altered in IDCM. Likewise, these changes were accompanied by significant metabolic differences. Further differential analysis displayed that 18 and 14 specific metabolites uniquely changed in ICM and IDCM, respectively. The heatmap was generated to display the association between genera and metabolites. Receiver operating characteristic curve (ROC) analysis confirmed the predictive value of the distinct microbial-metabolite features in disease status. The results showed that microbial (area under curve, AUC = 0.95) and metabolic signatures (AUC = 0.84) were effective in discriminating ICM from HC. Based on the specific microbial and metabolic features, the patients with IDCM could be separated from HC with an AUC of 0.80 and 0.87, respectively. Furthermore, the gut microbial genus (AUC = 0.88) and metabolite model (AUC = 0.89) were comparable in predicting IDCM from ICM. Especially, the combination of fecal microbial-metabolic features improved the ability to differentiate IDCM from ICM with an AUC of 0.96. CONCLUSION: Our findings highlighted the alterations of gut microbiota and metabolites in different types of cardiomyopathies, providing insights into the pathophysiological mechanisms of myocardial diseases. Moreover, multi-omics analysis of fecal samples holds promise as a non-invasive tool for distinguishing disease status.

Abnormal adiposity indices are associated with an increased risk of diabetes in a non-obese Asian population.

OBJECTIVES: The aim of this study was to evaluate the association between adiposity indices and the risk of incident diabetes and to compare their predictive ability in non-obese healthy individuals. STUDY DESIGN: Population-based cohort study. METHODS: Data were taken from the NAGALA research study, which enrolled Japanese adults aged 18-79 years. Cox regression was used to evaluate the association between adiposity indices (including waist circumference [WC], waist-to-height ratio [WHtR], lipid accumulation product index [LAP], body roundness index [BRI], visceral adiposity index [VAI] and Chinese visceral adiposity index [CVAI]) and diabetes risk. The performance of the indices for predicting diabetes was explored using area under the receiver operating characteristic curve (AUC). A Chinese community-based population was used for validation. RESULTS: A total of 12,940 healthy Japanese individuals with normal body mass index and glycaemic levels were included and were followed up for a median of 6 years. Multivariable Cox models revealed a positive and significant association between all indices and incident diabetes, with the hazard ratios for the highest quartile of the indices ranging from 1.89 to 2.90 (all P-values < 0.01). A non-linear association between WC, BRI and VAI and a linear association between WHtR, LAP and CVAI and diabetes risk were observed. CVAI, VAI and LAP had comparable ability in predicting diabetes, with the highest AUC being 0.733 for CVAI. Data from 10,830 Chinese individuals confirmed these results. CONCLUSIONS: Adiposity indices are associated with incident diabetes in healthy non-obese individuals. Participants in the highest quartile of WC, WHtR, LAP, BRI, VAI and CVAI had an increased risk of developing diabetes.

Interleukin-37 suppresses ICAM-1 expression in parallel with NF-κB down-regulation following TLR2 activation of human coronary artery endothelial cells.

INTRODUCTION: The inflammatory receptor Toll-like receptors (TLRs) activation could induce endothelial inflammatory responses, which plays an important role in the development of many diseases including atherosclerosis. We already found that TLR2 activation of Peptidoglycan (PGN) stimulation could increase intercellular adhesion molecule-1 (ICAM-1) expression in HCAECs. Since anti-inflammatory cytokine interleukin (IL)-37 exhibits intra- and extracellular properties for suppressing innate inflammation, we want to investigate whether IL-37 suppresses ICAM-1 expression and this effect is in parallel with the inhibition of nuclear factor kappa B (NF-κB) activation upon PGN stimulation in HCAECs. METHODS: HCAECs were treated with IL-37-transfection plasmid or silent mRNA or nothing for 24h, and we test IL-37 expression by immunoblotting. Same treatments prior to PGN stimulation (10µg/ml), we analyzed the expression of ICAM-1 and NF-κB mRNA at 0, 30min, 1 and 2h by real-time PCR. ICAM-1 protein at 24h and NF-κB activation at 0-2h were measured by immunoblotting. RESULTS: IL-37 and silent IL-37 transfection change the expression of IL-37 protein. Stimulation of PGN increased both NF-κB activation and ICAM-1 expression at mRNA and protein level, but these inflammatory cytokines' expression was significantly decreased in IL-37-transfection cells. Interestingly, both NF-κB activation and ICAM-1 expression were significantly increased when IL-37 was silent. CONCLUSIONS: As an anti-inflammatory cytokine, IL-37 could decrease both NF-κB and ICAM-1 expression upon TLR2 activation in HCAECs. The suppressed effect of IL-37 on ICAM-1 may be due to its inhibition on NF-κB.