No abstract

Acute myocardial infarction (AMI) continues as the main cause of morbidity and mortality worldwide. Interestingly, emerging evidence highlights the role of gut microbiota in regulating the pathogenesis of coronary heart disease, but few studies have systematically assessed the alterations and influence of gut microbiota in AMI patients. As one approach to address this deficiency, in this study the composition of fecal microflora was determined from Chinese AMI patients and links between gut microflora and clinical features and functional pathways of AMI were assessed. Fecal samples from 30 AMI patients and 30 healthy controls were collected to identify the gut microbiota composition and the alterations using bacterial 16S rRNA gene sequencing. We found that gut microflora in AMI patients contained a lower abundance of the phylum Firmicutes and a slightly higher abundance of the phylum Bacteroidetes compared to the healthy controls. Chao1 (P = 0.0472) and PD-whole-tree (P = 0.0426) indices were significantly lower in the AMI versus control group. The AMI group was characterized by higher levels of the genera Megasphaera, Butyricimonas, Acidaminococcus, and Desulfovibrio, and lower levels of Tyzzerella 3, Dialister, [Eubacterium] ventriosum group, Pseudobutyrivibrio, and Lachnospiraceae ND3007 group as compared to that in the healthy controls (P < 0.05). The common metabolites of these genera are mostly short-chain fatty acids, which reveals that the gut flora is most likely to affect the occurrence and development of AMI through the short-chain fatty acid pathway. In addition, our results provide the first evidence revealing remarkable differences in fecal microflora among subgroups of AMI patients, including the STEMI vs. NSTEMI, IRA-LAD vs. IRA-Non-LAD and Multiple (≥2 coronary stenosis) vs. Single coronary stenosis groups. Several gut microflora were also correlated with clinically significant characteristics of AMI patients, including LVEDD, LVEF, serum TnI and NT-proBNP, Syntax score, counts of leukocytes, neutrophils and monocytes, and fasting serum glucose levels. Taken together, the data generated enables the prediction of several functional pathways as based on the fecal microfloral composition of AMI patients. Such information may enhance our comprehension of AMI pathogenesis.

Chronic heart failure (CHF) is the final outcome of almost all forms of cardiovascular diseases, remaining the main cause of mortality worldwide. Accumulating evidence is focused on the roles of gut microbial community in cardiovascular disease, but few studies have unveiled the alterations and further directions of gut microbiota in severe CHF patients. Aimed to investigate this deficiency, fecal samples from 29 CHF patients diagnosed with NYHA Class III-IV and 30 healthy controls were collected and then analyzed using bacterial 16S rRNA gene sequencing. As a result, there were many significant differences between the two groups. Firstly, the phylum Firmicutes was found to be remarkably decreased in severe CHF patients, and the phylum Proteobacteria was the second most abundant phyla in severe CHF patients instead of phylum Bacteroides strangely. Secondly, the α diversity indices such as chao1, PD-whole-tree and Shannon indices were significantly decreased in the severe CHF versus the control group, as well as the notable difference in β-diversity between the two groups. Thirdly, our result revealed a remarkable decrease in the abundance of the short-chain fatty acids (SCFA)-producing bacteria including genera Ruminococcaceae UCG-004, Ruminococcaceae UCG-002, Lachnospiraceae FCS020 group, Dialister and the increased abundance of the genera in Enterococcus and Enterococcaceae with an increased production of lactic acid. Finally, the alternation of the gut microbiota was presumably associated with the function including Cell cycle control, cell division, chromosome partitioning, Amino acid transport and metabolism and Carbohydrate transport and metabolism through SCFA pathway. Our findings provide the direction and theoretical knowledge for the regulation of gut flora in the treatment of severe CHF.

Diabetic dyslipidemia is a common condition in patients with Type 2 diabetes mellitus (T2DM). However, with the increasing application of statins which mainly decrease low-density lipoprotein cholesterol (LDL-C) levels, clinical trials and meta-analysis showed a clearly increase of the incidence of new-onset DMs, partly due to genetic factors. To determine whether a causal relationship exists between LDL-C and T2DM, we conducted a two-sample Mendelian Randomization (MR) analysis using genetic variations as instrumental variables (IVs). Initially, 29 SNPs significantly related to LDL-C (P≤ 5.0×10-8) were selected as based on results from the study of Henry et al, which processed loci data influencing lipids identified by the Global Lipids Genetics Consortium (GLGC) from 188,577 individuals of European ancestry. While 6 SNPs related to T2DM (P value < 5×10-2) were deleted, with the remaining 23 SNPs without LD eventually being deemed as IVs. The combined effect of all these 23 SNPs on T2DM, as generated with use of the penalized robust inversevariance weighted (IVW) method (Beta value 0.24, 95%CI 0.087~0.393, P-value=0.002) demonstrated that elevated LDL-C levels significantly increased the risk of T2DM. The relationship between LDL-C and Type 1 diabetes mellitus (T1DM) with this analysis producing negative pooled results (Beta value-0.202, 95%CI-2.888~2.484, P-value=0.883).