Association Study of Gut Flora in Coronary Heart Disease through High-Throughput Sequencing.
Cui Li,Zhao Tingting,Hu Haibing,Zhang Wen,Hua Xiuguo
BioMed research international
We aimed to explore the impact of gut microbiota in coronary heart disease (CHD) patients through high-throughput sequencing. A total of 29 CHD in-hospital patients and 35 healthy volunteers as controls were included. Nucleic acids were extracted from fecal samples, followed by diversity and principal coordinate analysis (PCoA). Based on unweighted UniFrac distance matrices, unweighted-pair group method with arithmetic mean (UPGMA) trees were created. After data optimization, an average of 121312 ± 19293 reads in CHD patients and 234372 ± 108725 reads in controls was obtained. Reads corresponding to 38 phyla, 90 classes, and 584 genera were detected in CHD patients, whereas 40 phyla, 99 classes, and 775 genera were detected in controls. The proportion of phylum Bacteroidetes (56.12%) was lower and that of phylum Firmicutes was higher (37.06%) in CHD patients than those in the controls (60.92% and 32.06%, < 0.05). PCoA and UPGMA tree analysis showed that there were significant differences of gut microbial compositions between the two groups. The diversity and compositions of gut flora were different between CHD patients and healthy controls. The incidence of CHD might be associated with the alteration of gut microbiota.
Alterations in the gut microbiome and metabolism with coronary artery disease severity.
Liu Honghong,Chen Xi,Hu Xiaomin,Niu Haitao,Tian Ran,Wang Hui,Pang Haiyu,Jiang Lingjuan,Qiu Bintao,Chen Xiuting,Zhang Yang,Ma Yiyangzi,Tang Si,Li Hanyu,Feng Siqin,Zhang Shuyang,Zhang Chenhong
BACKGROUND:Coronary artery disease (CAD) is associated with gut microbiota alterations in different populations. Gut microbe-derived metabolites have been proposed as markers of major adverse cardiac events. However, the relationship between the gut microbiome and the different stages of CAD pathophysiology remains to be established by a systematic study. RESULTS:Based on multi-omic analyses (sequencing of the V3-V4 regions of the 16S rRNA gene and metabolomics) of 161 CAD patients and 40 healthy controls, we found that the composition of both the gut microbiota and metabolites changed significantly with CAD severity. We identified 29 metabolite modules that were separately classified as being positively or negatively correlated with CAD phenotypes, and the bacterial co-abundance group (CAG) with characteristic changes at different stages of CAD was represented by Roseburia, Klebsiella, Clostridium IV and Ruminococcaceae. The result revealed that certain bacteria might affect atherosclerosis by modulating the metabolic pathways of the host, such as taurine, sphingolipid and ceramide, and benzene metabolism. Moreover, a disease classifier based on differential levels of microbes and metabolites was constructed to discriminate cases from controls and was even able to distinguish stable coronary artery disease from acute coronary syndrome accurately. CONCLUSION:Overall, the composition and functions of the gut microbial community differed from healthy controls to diverse coronary artery disease subtypes. Our study identified the relationships between the features of the gut microbiota and circulating metabolites, providing a new direction for future studies aiming to understand the host-gut microbiota interplay in atherosclerotic pathogenesis.
Bacteroides vulgatus and Bacteroides dorei Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis.
Yoshida Naofumi,Emoto Takuo,Yamashita Tomoya,Watanabe Hikaru,Hayashi Tomohiro,Tabata Tokiko,Hoshi Namiko,Hatano Naoya,Ozawa Genki,Sasaki Naoto,Mizoguchi Taiji,Amin Hilman Zulkifli,Hirota Yushi,Ogawa Wataru,Yamada Takuji,Hirata Ken-Ichi
BACKGROUND:It is increasingly recognized that gut microbiota play a pivotal role in the development of atherosclerotic cardiovascular disease. Previously, we have reported that the abundance of genus Bacteroides is lower in patients with coronary artery disease (CAD) than in patients without CAD with coronary risk factors or in healthy volunteers. However, it remains unclear which and how specific gut bacteria contribute to the progression of atherosclerosis. METHODS:We recruited patients with CAD patients and controls without CAD with coronary risk factors. We then compared gut microbial composition using 16S ribosomal RNA gene sequencing in fecal samples to detect species with differential abundance between 2 groups. Subsequently, we used atherosclerosis-prone mice to study the mechanisms underlying the relationship between such species and atherosclerosis. RESULTS:Human fecal 16S ribosomal RNA gene sequencing revealed a significantly lower abundance of Bacteroides vulgatus and Bacteroides dorei in patients with CAD. This significant differential abundance was confirmed by quantitative polymerase chain reaction. Gavage with live B. vulgatus and B. dorei attenuated atherosclerotic lesion formation in atherosclerosis-prone mice, markedly ameliorating endotoxemia followed by decreasing gut microbial lipopolysaccharide production, effectively suppressing proinflammatory immune responses. Furthermore, fecal lipopolysaccharide levels in patients with CAD were significantly higher and negatively correlated with the abundance of B. vulgatus and B. dorei. CONCLUSIONS:Our translational research findings identify a previously unknown link between specific gut bacteria and atherosclerosis. Treatment with live B. vulgatus and B. dorei may help prevent CAD. CLINICAL TRIAL REGISTRATION:URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018051 . Unique identifier: UMIN000015703.
The gut microbiome in coronary artery disease and heart failure: Current knowledge and future directions.
Trøseid Marius,Andersen Geir Øystein,Broch Kaspar,Hov Johannes Roksund
Host-microbiota interactions involving inflammatory and metabolic pathways have been linked to the pathogenesis of multiple immune-mediated diseases and metabolic conditions like diabetes and obesity. Accumulating evidence suggests that alterations in the gut microbiome could play a role in cardiovascular disease. This review focuses on recent advances in our understanding of the interplay between diet, gut microbiota and cardiovascular disease, with emphasis on heart failure and coronary artery disease. Whereas much of the literature has focused on the circulating levels of the diet- and microbiota-dependent metabolite trimethylamine-N-oxide (TMAO), several recent sequencing-based studies have demonstrated compositional and functional alterations in the gut microbiomes in both diseases. Some microbiota characteristics are consistent across several study cohorts, such as a decreased abundance of microbes with capacity for producing butyrate. However, the published gut microbiota studies generally lack essential covariates like diet and clinical data, are too small to capture the substantial variation in the gut microbiome, and lack parallel plasma samples, limiting the ability to translate the functional capacity of the gut microbiomes to actual function reflected by circulating microbiota-related metabolites. This review attempts to give directions for future studies in order to demonstrate clinical utility of the gut-heart axis.
Coronary heart disease and intestinal microbiota.
Liu Lin,He Xuyu,Feng Yingqing
Coronary artery disease
Changes in human body systems influence metabolism and may cause disease. The intestinal microbiota influence health and is itself influenced by factors including diet and drugs. Investigation of the relationship of the intestinal microbiota and chronic conditions like coronary heart disease (CHD) has been facilitated by advances in sequencing technology. Some studies have identified changes in the composition and the metabolism of intestinal microbiota in patients with CHD, including increases in phyla Bacteroidetes and Proteobacteria and decreases in phyla Firmicutes and Fusobacteria. The ratio of two metabolites of intestinal bacteria, trimethylamine and trimethylamine N-oxide, has been found to be related to CHD. This review summarizes recent research to provide ideas for further research on the relationships between intestinal microbiota and CHD and on the preventive measures for CHD.
Analysis of changes in intestinal flora and intravascular inflammation and coronary heart disease in obese patients.
Li Xv,Li Chuantao
Experimental and therapeutic medicine
Changes in intestinal flora in obese patients and intravascular C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and coronary heart disease (CHD) were analyzed. A total of 75 cases of obese patients were divided into obesity (OB) alone (n=40) and OB with CHD group (n=35). There was no statistically significant difference in age, sex, pre-existing basic diabetes, history of hypertension, and body mass index (P>0.05). Results showed that total bacterial load of CHD was obviously higher than that of OB group. The uric acid decomposed by intestinal flora (IFUA) and blood uric acid levels in CHD were higher than those in OB group, but the fecal uric acid level was lower than that of OB group (P<0.05). Levels of inflammatory factors in CHD, were significantly higher than those in OB group (P<0.05). Correlation analyses showed that the intestinal flora total load and CRP were positively correlated (r=0.793, P<0.001). Intestinal flora and Gensini score were also positively related to total load (r=0.893, P=0.893). Furthermore, CRP and Gensini score were positively related (r=0.796, P<0.796). IFUA and Gensini score were positively related to (r=0.647, P<0.001). Over-reaction in the flammation system in obese patients may lead to intestinal flora disorder, disturbance and also increased levels of IFUA and inflammatory factors.
Correlations of changes in inflammatory factors, glucose and lipid metabolism indicators and adiponectin with alterations in intestinal flora in rats with coronary heart disease.
Peng Y,Zhang N,Li W-J,Tan K,Zhou Y,She C,Chen H-N
European review for medical and pharmacological sciences
OBJECTIVE:The aim of this study was to explore the correlations of changes in inflammatory factors, glucose and lipid metabolism indicators and adiponectin with alterations in intestinal flora in rats with coronary heart disease. MATERIALS AND METHODS:A total of 30 male specific pathogen-free rats were randomly assigned into two groups, including: blank group (n=15) and coronary heart disease group (n=15). The rats in the coronary heart disease group were given high-fat diets and pituitrin to establish the model of coronary heart disease. Meanwhile, rats in the blank group were administered with an equal volume of double-distilled water. The alterations in the intestinal flora of rats were detected in the two groups, respectively. In addition, the changes in the levels of inflammatory factors, glucose and lipid metabolism indicators, adiponectin, creatine kinase (CK) and its isoenzyme, as well as troponin, were also examined. RESULTS:Statistically, significant differences in the levels of glucose and lipid metabolism indicators low-density lipoprotein (LDL) (p=0.040), total cholesterol (TC) (p=0.039), high-density lipoprotein (HDL) (p=0.044), triglyceride (TG) (p=0.000) and blood glucose (p=0.046) were observed between the rats in the coronary heart disease group and blank group. The content of all the glucose and lipid metabolism indicators (except HDL) in coronary heart disease group was significantly higher than the blank group (p<0.05). The rats in the coronary heart disease group had evidently higher levels of CK (p=0.000) and its isoenzyme (p=0.019), as well as troponin (p=0.021), than those in the blank group. The level of serum adiponectin in rats in coronary heart disease group was distinctly lower than that in the blank group, showing statistically significant differences (p<0.05). Besides, the levels of the inflammatory factors interleukin (IL)-2 (p=0.011), transforming growth factor (TGF)-β (p=0.048), tumor necrosis factor-α (TNF-α) (p=0.025) and IL-6 (p=0.038) in rats in the coronary heart disease group were dramatically higher than those in blank group. Rats in coronary heart disease group had remarkably more Actinobacteria, Desulfovibrio, Aristipus and Escherichia coli in the intestine. Meanwhile, the abundance of Flavobacterium, Burkhofer and some probiotics increased significantly in the intestine of rats in blank group (p<0.05). The changes in the abundance of Actinobacteria, Desulfovibrio, Aristipus and Escherichia coli in the intestine of rats were probably correlated with increased levels of glucose and lipid metabolism indicators, inflammatory factors and adiponectin in coronary heart disease group. Moreover, the abundance of intestinal probiotics such as Bifidobacterium and Lactobacillus in rats in coronary heart disease group was notably lower than that in blank group (p<0.05). The decline in the abundance of such intestinal probiotics as Bifidobacterium and Lactobacillus was correlated with the changes in the levels of glucose and lipid metabolism indicators, inflammatory factors and adiponectin. In addition, decreased levels of probiotics weakened normal physiological functions of the intestine and promoted disease progression. CONCLUSIONS:Inflammatory factors, glucose and lipid metabolism indicators and adiponectin have evident changes in rats with coronary heart disease, which may be correlated with the alterations in the intestinal flora.