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1.
Am J Physiol Heart Circ Physiol ; 318(3): H590-H603, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32031871

RESUMO

Metabolic syndrome (MetS) is a composite of cardiometabolic risk factors, including obesity, dyslipidemia, hypertension, and insulin resistance, with a range of secondary sequelae such as nonalcoholic fatty liver disease and diastolic heart failure. This syndrome has been identified as one of the greatest global health challenges of the 21st century. Herein, we examine whether a porcine model of diet- and mineralocorticoid-induced MetS closely mimics the cardiovascular, metabolic, gut microbiota, and functional metataxonomic phenotype observed in human studies. Landrace pigs with deoxycorticosterone acetate-induced hypertension fed a diet high in fat, salt, and sugar over 12 wk were assessed for hyperlipidemia, hyperinsulinemia, and immunohistologic, echocardiographic, and hemodynamic parameters, as well as assessed for microbiome phenotype and function through 16S rRNA metataxonomic and metabolomic analysis, respectively. All MetS animals developed obesity, hyperlipidemia, insulin resistance, hypertension, fatty liver, structural cardiovascular changes including left ventricular hypertrophy and left atrial enlargement, and increased circulating saturated fatty acid levels, all in keeping with the human phenotype. A reduction in α-diversity and specific microbiota changes at phylum, family, and genus levels were also observed in this model. Specifically, this porcine model of MetS displayed increased abundances of proinflammatory bacteria coupled with increased circulating tumor necrosis factor-α and increased secondary bile acid-producing bacteria, which substantially impacted fibroblast growth factor-19 expression. Finally, a significant decrease in enteroprotective bacteria and a reduction in short-chain fatty acid-producing bacteria were also noted. Together, these data suggest that diet and mineralocorticoid-mediated development of biochemical and cardiovascular stigmata of metabolic syndrome in pigs leads to temporal gut microbiome changes that mimic key gut microbial population signatures in human cardiometabolic disease.NEW & NOTEWORTHY This study extends a prior porcine model of cardiometabolic syndrome to include systemic inflammation, fatty liver, and insulin sensitivity. Gut microbiome changes during evolution of porcine cardiometabolic disease recapitulate those in human subjects with alterations in gut taxa associated with proinflammatory bacteria, bile acid, and fatty acid pathways. This clinical scale model may facilitate design of future interventional trials to test causal relationships between gut dysbiosis and cardiometabolic syndrome at a systemic and organ level.


Assuntos
Microbioma Gastrointestinal/fisiologia , Hipertensão/microbiologia , Resistência à Insulina/fisiologia , Síndrome Metabólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Animais , Glicemia/metabolismo , Colesterol/sangue , Dieta Hiperlipídica , Modelos Animais de Doenças , Ecocardiografia , Feminino , Hipertensão/metabolismo , Inflamação/metabolismo , Inflamação/microbiologia , Insulina/sangue , Síndrome Metabólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Suínos , Triglicerídeos/sangue
2.
Clin Sci (Lond) ; 134(2): 289-302, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31961431

RESUMO

Preeclampsia (PE) is regarded as a pregnancy-associated hypertension disorder that is related to excessive inflammatory responses. Although the gut microbiota (GM) and short-chain fatty acids (SCFAs) have been related to hypertension, their effects on PE remain unknown. We determined the GM abundance and faecal SCFA levels by 16S ribosomal RNA (rRNA) sequencing and gas chromatography, respectively, using faecal samples from 27 patients with severe PE and 36 healthy, pregnant control subjects. We found that patients with PE had significantly decreased GM diversity and altered GM abundance. At the phylum level, patients with PE exhibited decreased abundance of Firmicutes albeit increased abundance of Proteobacteria; at the genus level, patients with PE had lower abundance of Blautia, Eubacterium_rectale, Eubacterium_hallii, Streptococcus, Bifidobacterium, Collinsella, Alistipes, and Subdoligranulum, albeit higher abundance of Enterobacter and Escherichia_Shigella. The faecal levels of butyric and valeric acids were significantly decreased in patients with PE and significantly correlated with the above-mentioned differential GM abundance. We predicted significantly increased abundance of the lipopolysaccharide (LPS)-synthesis pathway and significantly decreased abundance of the G protein-coupled receptor (GPCR) pathway in patients with PE, based on phylogenetic reconstruction of unobserved states (PICRUSt). Finally, we evaluated the effects of oral butyrate on LPS-induced hypertension in pregnant rats. We found that butyrate significantly reduced the blood pressure (BP) in these rats. In summary, we provide the first evidence linking GM dysbiosis and reduced faecal SCFA to PE and demonstrate that butyrate can directly regulate BP in vivo, suggesting its potential as a therapeutic agent for PE.


Assuntos
Ácidos Graxos Voláteis/análise , Microbioma Gastrointestinal/fisiologia , Hipertensão/fisiopatologia , Pré-Eclâmpsia/fisiopatologia , Adulto , Animais , Bactérias/classificação , Bactérias/genética , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Butiratos/administração & dosagem , Butiratos/análise , Butiratos/metabolismo , Ácidos Graxos Voláteis/metabolismo , Fezes/química , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Humanos , Hipertensão/metabolismo , Hipertensão/microbiologia , Ácidos Pentanoicos/análise , Ácidos Pentanoicos/metabolismo , Dinâmica Populacional , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/microbiologia , Gravidez , RNA Ribossômico 16S/genética , Ratos Sprague-Dawley
3.
Nutr Metab Cardiovasc Dis ; 29(12): 1408-1417, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31640890

RESUMO

BACKGROUND AND AIM: High-fat (HF) diet consumption has been associated with gut dysbiosis and increased risk of dyslipidemia, type 2 diabetes mellitus and hypertension. Probiotic administration has been suggested as a safe therapeutic strategy for the treatment of cardiometabolic disorders. This study was designed to assess the effects of probiotic Lactobacillus (L.) fermentum 296, a fruit-derived bacteria strain, against cardiometabolic disorders induced by HF diet. METHODS AND RESULTS: Male Wistar rats were divided into control diet (CTL); HF diet; and HF diet treated with Lactobacillus fermentum 296 (HF + Lf 296). The L. fermentum 296 strain at 1 × 109 colony forming units (CFU)/ml were daily administered by oral gavage for 4 weeks. The results showed that rats fed with HF diet displayed insulin resistance, reduced Lactobacillus spp. counts in feces, serum lipids, and oxidative profile. Rats fed on HF diet also demonstrated augmented blood pressure associated with sympathetic hyperactivity and impaired baroreflex control. The administration of L. fermentum 296 for 4 weeks recovered fecal Lactobacillus sp. counts and alleviated hyperlipidemia, sympathetic hyperactivity, and reduced systolic blood pressure in HF rats without affecting baroreflex sensibility. CONCLUSION: Our results suggest the ability of L. fermentum 296 improve biochemical and cardiovascular parameters altered in cardiometabolic disorders.


Assuntos
Dieta Hiperlipídica , Dislipidemias/terapia , Microbioma Gastrointestinal , Hipertensão/terapia , Resistência à Insulina , Lactobacillus fermentum/crescimento & desenvolvimento , Síndrome Metabólica/terapia , Probióticos/farmacologia , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Pressão Sanguínea , Modelos Animais de Doenças , Disbiose , Dislipidemias/sangue , Dislipidemias/microbiologia , Hipertensão/microbiologia , Hipertensão/fisiopatologia , Insulina/sangue , Lipídeos/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/microbiologia , Síndrome Metabólica/fisiopatologia , Ratos Wistar
4.
Biol Pharm Bull ; 42(9): 1482-1490, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474709

RESUMO

Zhengganxifeng decoction (ZGXFD) is a traditional Chinese medicinal formula, from "Medical Zhong parameter West recorded" by Xichun Zhang, which has been applied to the treatment of clinical essential hypertension. Besides its effect in blood pressure reduction, ZGXFD is also known to be a radical therapy with little or no side effects. Compared with western medicines, Chinese medicinal formulas have the advantage of simultaneously attacking multiple targets. However, such a property brings trouble to the pharmacological studies of Chinese medicines. This study investigated the composition of gut microbiota in spontaneously hypertensive rats (SHR) treated with ZGXFD. ZGXFD was shown to cause similar effects in the treatment group as benazepril: both were able to reduce in SHR the microbial diversity, Firmicutes to Bacteroidetes (F/B) ratio and coccus to bacillus (C/B) ratio. Meanwhile, ZGXFD can maintain the integrity of intestinal mechanistic barrier and elevate the percentage of bacteria producing short chain fatty acids (SCFA). By investigating renin-angiotensin system (RAS) system, we found that ZGXFD can decrease the expression of angiotensin-converting-enzyme (ACE) in lungs, which in turn causes a increase in AngI produces angiotensin1-7 (Ang1-7) and decrease in AngII. ZGXFD regulate blood pressure in SHR via RAS.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Animais , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/fisiologia , Hipertensão/microbiologia , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
5.
Nutrients ; 11(9)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443482

RESUMO

Excessive intake of saturated fat has been linked to hypertension. Gut microbiota and their metabolites, short-chain fatty acids (SCFAs), are known to be involved in the development of hypertension. We examined whether maternal and post-weaning high-fat (HF) diet-induced hypertension in adult male offspring is related to alterations of gut microbiota, mediation of SCFAs and their receptors, and downregulation of nutrient-sensing signals. Female Sprague-Dawley rats received either a normal diet (ND) or HF diet (D12331, Research Diets) during pregnancy and lactation. Male offspring were put on either the ND or HF diet from weaning to 16 weeks of age, and designated to four groups (maternal diet/post-weaning diet; n = 8/group): ND/ND, HF/ND, ND/HF, and HF/HF. Rats were sacrificed at 16 weeks of age. Combined HF/HF diets induced elevated blood pressure (BP) and increased body weight and kidney damage in male adult offspring. The rise in BP is related to a downregulated AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor co-activator 1α (PGC-1α) pathway. Additionally, HF/HF diets decreased fecal concentrations of propionate and butyrate and decreased G protein-coupled receptor 41 (GPR41), but increased olfactory receptor 78 (Oflr78) expression. Maternal HF diet has differential programming effects on the offspring's microbiota at 3 and 16 weeks of age. Combined HF/HF diet induced BP elevation was associated with an increased Firmicutes to Bacteroidetes ratio, increased abundance of genus Akkermansia and phylum Verrucomicrobia, and reduced abundance in genus Lactobacillus. Maternal gut microbiota-targeted dietary interventions might be reprogramming strategies to protect against programmed hypertension in children and their mothers on consumption of a fat-rich diet.


Assuntos
Bactérias/crescimento & desenvolvimento , Pressão Sanguínea , Dieta Hiperlipídica , Microbioma Gastrointestinal , Hipertensão/etiologia , Intestinos/microbiologia , Efeitos Tardios da Exposição Pré-Natal , Proteínas Quinases Ativadas por AMP/metabolismo , Fatores Etários , Fenômenos Fisiológicos da Nutrição Animal , Animais , Bactérias/metabolismo , Modelos Animais de Doenças , Feminino , Hipertensão/metabolismo , Hipertensão/microbiologia , Hipertensão/fisiopatologia , Córtex Renal/metabolismo , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Gravidez , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas-G/metabolismo , Receptores Odorantes/metabolismo , Desmame , Ganho de Peso
6.
Int J Med Sci ; 16(6): 872-881, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31337961

RESUMO

Hypertension is the main risk factor for cerebral stroke and death resulting from cerebral stroke. Current association studies on hypertension and intestinal microbiota focus on patients with hypertension (HTN); however, no investigations involving patients with isolated diastolic hypertension (IDH) or systolic hypertension (SH) have been conducted to date. In this study, fecal samples from 62 cases with normal blood pressure (BP) and 67 cases with high BP were used for 16S amplicon sequencing. Sixty-one cases of HTN and 61 corresponding cases with normal BP were obtained by propensity score matching (PSM), and differential analysis was conducted using the DEseq2 package. PSM was also used to match six IDH patients with six controls and to match 35 cases of SH with 35 controls. There were 54 differential genera between the HTN and normal BP groups, and there were five differential genera between the IDH and normal BP groups. There were 38 differential genera between the SH and normal BP groups, including Christensenella. Bayesian network analysis showed that variations in BP influenced microbial abundance. Pearson's correlation analysis showed that bacterial abundance is correlated with BP. Significant differences between the intestinal microbiota of high and normal BP groups were observed. Gut microbiota dysbiosis differed among HTN, IDH, and SH patients. In particular, diastolic blood pressure (DBP) and systolic blood pressure (SBP) were related to different intestinal microbiota.


Assuntos
Pressão Sanguínea/fisiologia , Disbiose/microbiologia , Microbioma Gastrointestinal/fisiologia , Hipertensão/microbiologia , Idoso , Bactérias/isolamento & purificação , Determinação da Pressão Arterial , Estudos de Casos e Controles , Disbiose/fisiopatologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
7.
Hypertension ; 74(4): 1005-1013, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31352822

RESUMO

Gut microbiota may influence blood pressure (BP), namely via end products of carbohydrate fermentation. After informed consent, male volunteers were prospectively categorized into 3 groups upon European Society of Hypertension criteria based on 24-hour ambulatory BP measurements: (1) hypertension, (2) borderline hypertension, and (3) normotension. Stool, urine and serum samples were collected in fasting conditions. Gut microbiota was characterized by 16S amplicon sequencing. Metabolomics, including quantification of short-chain fatty acids, was conducted using nuclear magnetic resonance. Two-way ANOVA combined with Tukey post hoc test, as well as multiple permutation test and Benjamini-Hochberg-Yekutieli false discovery rate procedure, was used. The cohort included 54 males: 38 hypertensive (including 21 under treatment), 7 borderline, and 9 normotensive. No significant difference was observed between groups concerning age, body mass index, smoking habits, and weekly alcohol consumption. The genus Clostridium sensu stricto 1 positively correlated with BP levels in nontreated patients (n=33). This correlation was significant after multiple permutation tests but was not substantiated following false discovery rate adjustment. Short-chain fatty acid levels were significantly different among groups, with higher stool levels of acetate, butyrate, and propionate in hypertensive versus normotensive individuals. No difference was observed in serum and urine metabolomes. Correlation between stool metabolome and 24-hour BP levels was evidenced, with R2 reaching 0.9. Our pilot study based on 24-hour ambulatory BP measurements, 16S amplicon sequencing, and metabolomics supports an association between gut microbiota and BP homeostasis, with changes in stool abundance of short-chain fatty acids.


Assuntos
Pressão Sanguínea/fisiologia , Ácidos Graxos Voláteis/análise , Fezes/química , Microbioma Gastrointestinal/fisiologia , Hipertensão/fisiopatologia , Adulto , Humanos , Hipertensão/microbiologia , Masculino , Metaboloma , Pessoa de Meia-Idade , Projetos Piloto
8.
Nutrients ; 11(7)2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31261830

RESUMO

Gut microbiota dysbiosis has been recognized as having key importance in obesity- and metabolic-related diseases. Although there is increasing evidence of the potential benefits induced by probiotics in metabolic disturbances, there is a lack of large cross-sectional studies to assess population-based prevalence of probiotic intake and metabolic diseases. Our aim was to evaluate the association of probiotic ingestion with obesity, type 2 diabetes, hypertension, and dyslipidemia. A cross-sectional study was designed using data from the National Health and Nutrition Examination Survey (NHANES), 1999-2014. Probiotic ingestion was considered when a subject reported consumption of yogurt or a probiotic supplement during the 24-hour dietary recall or during the Dietary Supplement Use 30-Day questionnaire. We included 38,802 adults and 13.1% reported probiotic ingestion. The prevalence of obesity and hypertension was lower in the probiotic group (obesity-adjusted Odds Ratio (OR): 0.84, 95% CI 0.76-0.92, p < 0.001; hypertension-adjusted OR: 0.79, 95% CI 0.71-0.88, p < 0.001). Accordingly, even after analytic adjustments, body mass index (BMI) was significantly lower in the probiotic group, as were systolic and diastolic blood pressure and triglycerides; high-density lipoprotein (HDL) was significantly higher in the probiotic group for the adjusted model. In this large-scale study, ingestion of probiotic supplements or yogurt was associated with a lower prevalence of obesity and hypertension.


Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Dislipidemias/prevenção & controle , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologia , Hipertensão/prevenção & controle , Obesidade/prevenção & controle , Probióticos/administração & dosagem , Iogurte/microbiologia , Adulto , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/microbiologia , Disbiose , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Dislipidemias/microbiologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/microbiologia , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/epidemiologia , Obesidade/microbiologia , Prevalência , Fatores de Proteção , Medição de Risco , Fatores de Risco , Estados Unidos/epidemiologia
9.
Int J Mol Med ; 44(2): 513-522, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173179

RESUMO

Hypertension has become a major risk factor for many diseases, including cardiovascular, cerebrovascular and kidney disorders. It has been reported that the composition of human gut microbiota is changed during the progression of cardiovascular and kidney diseases. The current study aimed to qualitatively and quantitatively compare the composition of gut microbiota between patients with hypertension and healthy controls. Fecal samples were collected from 50 patients diagnosed with grade 3 hypertension and 30 healthy controls. Touchdown PCR­denaturing gradient gel electrophoresis with primers specifically targeting the V3 region of 16S ribosomal RNA, and quantitative PCR, were performed to characterize all the samples. High­throughput sequencing of the V3­V4 regions was performed on 30 randomly selected samples. By comparing diversity and richness indices, the gut microbiome of the hypertensive individuals was found to be more diverse than that of the healthy controls. Among the main bacterial phlya that reside in the gut, Bacteroidetes, Firmicutes and Proteobacteria were dominant in all the samples; however the Firmicutes to Bacteroidetes ratio was variable, with a significant increase in the patients with hypertension compared with the healthy control group. In addition, at the genus level, there was an increased abundance of Prevotella_9, Megasphaera, Parasutterella and Escherichia­Shigella in patients with hypertension, while Bacteroides and Faecalibacterium were decreased. These results suggested that the human gut microbiota is altered in hypertension, and understanding the mechanism of these changes in microbial composition may open up new insights, and help to treat hypertension and other related diseases.


Assuntos
Microbioma Gastrointestinal , Hipertensão/microbiologia , Adulto , Idoso , Bacteroidetes/genética , Bacteroidetes/isolamento & purificação , Progressão da Doença , Feminino , Firmicutes/genética , Firmicutes/isolamento & purificação , Humanos , Hipertensão/patologia , Masculino , Pessoa de Meia-Idade , Filogenia , Proteobactérias/genética , Proteobactérias/isolamento & purificação , RNA Ribossômico 16S/genética
10.
High Blood Press Cardiovasc Prev ; 26(3): 217-225, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31236901

RESUMO

INTRODUCTION: A possible role of the oral microbiome, specifically oral nitrate reducing flora, in blood pressure (BP) homeostasis, if proven etiologic in nature, could lead to novel mechanism-based therapy to improve hypertension prevention and control. AIM: This cross-sectional study characterized and compared the oral microbiome between four study groups based on BP status among 446 postmenopausal women aged 53-82 years. METHODS: Three study groups were not taking hypertension medication and were separated based on BP, as follows: normal BP (systolic < 120 and diastolic < 80; N = 179), elevated BP/Stage I hypertension (systolic 120-139 or diastolic 80-90; N = 106), Stage II hypertension (systolic > 140 or diastolic > 90; N = 42). The forth group consisted of anyone taking hypertension medications, regardless of BP (N = 119). Subgingival microbiome composition was determined using 16S rRNA sequencing with the Illumina MiSeq platform. Kruskal-Wallis tests were used to compare species-level relative abundance of bacterial operational taxonomic units across the four groups. RESULTS: Sixty-five bacterial species demonstrated significant differences in relative abundance in women with elevated BP or using hypertension medication as compared to those with normal BP. After correction for multiple testing, two species, Prevotella oral (species 317) and Streptococcus oralis, remained significant and were lower in abundance among women taking antihypertension medications compared to those with normal BP (corrected P < 0.05). CONCLUSIONS: These data provide novel description of oral subgingival bacteria grouped according to BP status. Additional larger studies including functional analysis and prospective designs will help further assess the potential role of the oral microbiome in BP regulation and hypertension.


Assuntos
Bactérias/isolamento & purificação , Pressão Sanguínea , Hipertensão/microbiologia , Hipertensão/fisiopatologia , Microbiota , Boca/microbiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Bactérias/classificação , Bactérias/genética , Pressão Sanguínea/efeitos dos fármacos , Estudos Transversais , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Pessoa de Meia-Idade , Pós-Menopausa , Ribotipagem/métodos , Fatores de Risco , Fatores Sexuais
11.
Biol Sex Differ ; 10(1): 22, 2019 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-31023366

RESUMO

There has been intense interest in the role of the gut microbiome in human health and a broad range of diseases in recent years. In the context of cardiovascular disease, gut dysbiosis (defined as a change in the gut microbiome and the gut-epithelial barrier) has been linked to disturbances in blood pressure (BP) regulation. These findings build upon our understanding of the complex pathophysiology of essential hypertension. There are clear sex differences in the epidemiology of hypertension, with distinct trends in BP across the life-course in men and women. To date, a role for the gut microbiome in contributing to the sex differences in BP is yet to be clearly established. The purpose of this review is to summarise the current literature regarding how the gut microbiome differs between men and women and to investigate whether sex-determined differences in the gut microbiome influence the response to factors such as diet, obesity and inflammation. Finally, we will explore evidence for the possible interaction between sex-specific factors, including sex hormones and pregnancy, with the gut in the context of hypertension pathophysiology.


Assuntos
Pressão Arterial , Microbioma Gastrointestinal , Caracteres Sexuais , Animais , Feminino , Humanos , Hipertensão/microbiologia , Masculino , Gravidez
12.
Hypertension ; 73(5): 998-1006, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30905192

RESUMO

Animal models support a role for the gut microbiota in the development of hypertension. There has been a lack of epidemiological cohort studies to confirm these findings in human populations. We examined cross-sectional associations between measures of gut microbial diversity and taxonomic composition and blood pressure (BP) in 529 participants of the biracial (black and white) CARDIA study (Coronary Artery Risk Development in Young Adults). We sequenced V3-V4 regions of the 16S ribosomal RNA marker gene using DNA extracted from stool samples collected at CARDIA's Year 30 follow-up examination (2015-2016; aged 48-60 years). We quantified associations between BP (hypertension [defined as systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg or antihypertension medication use] and systolic BP) and within and between-person diversity measures. We conducted genera-specific multivariable-adjusted regression analysis, accounting for multiple comparisons using the false discovery rate. Hypertension and systolic BP were inversely associated with measures of α-diversity, including richness and the Shannon Diversity Index, and were distinguished with respect to principal coordinates based on a similarity matrix of genera abundance. Several specific genera were significantly associated with hypertension and systolic BP, though results were attenuated with adjustment for body mass index. Our findings support associations between within-person and between-person gut microbial community diversity and taxonomic composition and BP in a diverse population-based cohort of middle-aged adults. Future study is needed to define functional pathways that underlie observed associations and identify specific microbial targets for intervention.


Assuntos
Pressão Sanguínea/fisiologia , Microbioma Gastrointestinal/fisiologia , Hipertensão/fisiopatologia , Adolescente , Adulto , Anti-Hipertensivos/uso terapêutico , Estudos Transversais , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/microbiologia , Masculino , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
13.
Clin Investig Arterioscler ; 31(4): 178-185, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30737071

RESUMO

Cardiovascular disease remains the first cause of mortality in Western countries. New strategies for prevention and control of cardiovascular disease are needed. At the same time, the incidence of risk factors that lead to the development of this disease, such as obesity, hypertension and diabetes, continues to rise. Therefore, the search for new markers or mediators is a priority in most cardiovascular prevention programs. The study of the intestinal microbiota is emerging because it is known that intestinal microorganisms act collectively as an integrated organ, regulating multiple biological functions that can modulate cardiovascular risk factors and the pathogenic mechanisms of this process. This review considers the current situation regarding the influence of gut microbiota on cardiovascular disease and particularly, its influence on the main traditional risk factors that lead to cardiovascular disease, such as obesity, diabetes, hypertension and lipids.


Assuntos
Doenças Cardiovasculares/etiologia , Microbioma Gastrointestinal , Doenças Cardiovasculares/microbiologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/microbiologia , Humanos , Hipertensão/complicações , Hipertensão/microbiologia , Lipídeos/sangue , Obesidade/complicações , Obesidade/microbiologia , Fatores de Risco
14.
Biomed Pharmacother ; 112: 108580, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30784906

RESUMO

Obstructive sleep apnea (OSA) and high salt content in modern diet has been particularly implicated in systemic hypertension, leading to increased morbidity and mortality. Gut dysbiosis, associated with increased risk of systemic immunological imbalance, plays a causal role in the development of cardiovascular diseases. Here, we investigated the effect of Lactobacillus rhamnosus GG strain (LGG) on the development of hypertension induced by OSA and high salt diet. In this study, hypertension was modeled in rats by feeding a high salt diet (HSD) for 6 wk and exposuring to chronic intermittent hypoxia (CIH) during the sleep cycle. We found that OSA combined with HSD increased the severity of hypertension through increasing level of blood Trimethylamine-Oxide (TMAO), release of Th1-related cytokine (IFN-γ) and inhibition of anti-inflammatory cytokine (TGF-ß1), and affected the gut microbiome in rats, particularly by depleting Lactobacillus. In addition, expression of PERK1/2, PAkt and PmTOR increased in the aorta from rats with a CIH exposure and HSD. Consequently, treatment of model rats with LGG prevented aggravation of hypertension by reducing blood TMAO levels, modulating Th1/Th2 cytokine imbalance and suppressing phosphorylation levels of ERK1/2, Akt and mTOR. In line with these findings, our results connect high salt diet to the gut-immune axis and highlight the gut microbiome as a potential therapeutic target to counteract the development of OSA-induced hypertension basing on a high salt diet.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Hipertensão/metabolismo , Mediadores da Inflamação/metabolismo , Lactobacillus rhamnosus , Metilaminas/metabolismo , Apneia Obstrutiva do Sono/metabolismo , Cloreto de Sódio na Dieta/efeitos adversos , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Hipertensão/induzido quimicamente , Hipertensão/microbiologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/microbiologia , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Apneia Obstrutiva do Sono/induzido quimicamente , Apneia Obstrutiva do Sono/microbiologia
15.
Circ Res ; 124(5): 727-736, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30612527

RESUMO

RATIONALE: Increased microglial activation and neuroinflammation within autonomic brain regions have been implicated in sustained hypertension, and their inhibition by minocycline-an anti-inflammatory antibiotic-produces beneficial effects. These observations led us to propose a dysfunctional brain-gut communication hypothesis for hypertension. However, it has been difficult to reconcile whether an anti-inflammatory or antimicrobial action is the primary beneficial effect of minocycline in hypertension. Accordingly, we utilized chemically modified tetracycline-3 (CMT-3)-a derivative of tetracycline that has potent anti-inflammatory activity-to address this question. OBJECTIVE: Test the hypothesis that central administration of CMT-3 would inhibit microglial activation, attenuate neuroinflammation, alter selective gut microbial communities, protect the gut wall from developing hypertension-associated pathology, and attenuate hypertension. METHODS AND RESULTS: Rats were implanted with radiotelemetry devices for recording mean arterial pressure. Ang II (angiotensin II) was infused subcutaneously using osmotic mini-pumps to induce hypertension. Another osmotic mini-pump was surgically implanted to infuse CMT-3 intracerebroventricularly. Intracerebroventricular CMT- 3 infusion was also investigated in SHR (spontaneously hypertensive rats). Physiological, pathological, immunohistological parameters, and fecal microbiota were analyzed. Intracerebroventricular CMT-3 significantly inhibited Ang II-induced increases in number of microglia, their activation, and proinflammatory cytokines in the paraventricular nucleus of hypothalamus. Further, intracerebroventricular CMT-3 attenuated increased mean arterial pressure, normalized sympathetic activity, and left ventricular hypertrophy in Ang II rats, as well as in the SHR. Finally, CMT-3 beneficially restored certain gut microbial communities altered by Ang II and attenuated pathological alterations in gut wall. CONCLUSIONS: These observations demonstrate that inhibition of microglial activation alone was sufficient to induce significant antihypertensive effects. This was associated with unique changes in gut microbial communities and profound attenuation of gut pathology. They suggest, for the first time, a link between microglia and certain microbial communities that may have implications for treatment of hypertension.


Assuntos
Anti-Hipertensivos/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Intestinos/efeitos dos fármacos , Microglia/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Tetraciclinas/administração & dosagem , Angiotensina II , Animais , Antibacterianos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Pressão Arterial/efeitos dos fármacos , Sistema Nervoso Autônomo/efeitos dos fármacos , Sistema Nervoso Autônomo/fisiopatologia , Modelos Animais de Doenças , Hipertensão/microbiologia , Hipertensão/patologia , Hipertensão/fisiopatologia , Infusões Intraventriculares , Intestinos/inervação , Intestinos/microbiologia , Intestinos/patologia , Masculino , Microglia/patologia , Núcleo Hipotalâmico Paraventricular/patologia , Núcleo Hipotalâmico Paraventricular/fisiopatologia , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
16.
Curr Opin Nephrol Hypertens ; 28(2): 97-104, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30531472

RESUMO

PURPOSE OF REVIEW: To summarize evidence supporting that microorganisms colonizing our gastrointestinal tract, collectively known as the gut microbiota, are implicated in the development and maintenance of hypertension in experimental models. RECENT FINDINGS: The use of gnotobiotic (germ-free) mice has been essential for advancement in this area: they develop higher blood pressure (BP) if they receive faecal transplants from hypertensive patients compared to normotensive donors, and germ-free mice have a blunted response to angiotensin II. Experimental hypertension is consistently accompanied by changes in the composition of the gut microbiota. This is combined with a shift in microbial diversity and the deterioration of the gut epithelial barrier commonly referred to as gut dysbiosis. Restoration of normal gut biosis and microbiota alleviates and protects against the development of hypertension in both genetic and pharmacological models. This has been achieved by the use of antibiotics, faecal transplants between normotensive and hypertensive strains, and the use of prebiotics (i.e. food stuff that feeds the microbiota), probiotics (i.e. live bacteria) and gut metabolites (i.e. short-chain fatty acids). SUMMARY: Research into experimental hypertension supports that the gut microbiota contributes to the regulation of BP. Manipulation of the microbiota might represent a new tool to prevent hypertension.


Assuntos
Modelos Animais de Doenças , Disbiose/complicações , Microbioma Gastrointestinal , Vida Livre de Germes , Hipertensão/microbiologia , Animais , Pressão Sanguínea , Dieta , Suplementos Nutricionais , Disbiose/terapia , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Modelos Teóricos
17.
Curr Hypertens Rev ; 15(1): 40-46, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29895255

RESUMO

Arterial hypertension is a progressive cardiovascular syndrome arising from complex and interrelated etiologies. The human microbiome refers to the community of microorganisms that live in or on the human body. They influence human physiology by interfering in several processes such as providing nutrients and vitamins in Phase I and Phase II drug metabolism. The human gut microbiota is represented mainly by Firmicutes and Bacteroidetes and to a lesser degree by Actinobacteria and Proteobacteria, with each individual harbouring at least 160 such species. Gut microbiota contributes to blood pressure homeostasis and the pathogenesis of arterial hypertension through production, modification, and degradation of a variety of microbial-derived bioactive metabolites. Animal studies and to a lesser degree human research has unmasked relative mechanisms, mainly through the effect of certain microbiome metabolites and their receptors, outlining this relationship. Interventions to utilize these pathways, with probiotics, prebiotics, antibiotics and fecal microbiome transplantation have shown promising results. Personalized microbiome-based disease prediction and treatment responsiveness seem futuristic. Undoubtedly, a long way of experimental and clinical research should be pursued to elucidate this novel, intriguing and very promising horizon.


Assuntos
Pressão Arterial , Bactérias/crescimento & desenvolvimento , Microbioma Gastrointestinal , Hipertensão/microbiologia , Hipertensão/fisiopatologia , Intestinos/microbiologia , Animais , Anti-Hipertensivos/uso terapêutico , Pressão Arterial/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Modelos Animais de Doenças , Disbiose , Microbioma Gastrointestinal/efeitos dos fármacos , Interações Hospedeiro-Patógeno , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Probióticos/uso terapêutico , Fatores de Risco
18.
Curr Opin Cardiol ; 34(2): 225-232, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30575647

RESUMO

PURPOSE OF REVIEW: The human gut is populated by a complex community of microbiota that coexists with the host to maintain homeostasis. Accumulating evidence shows that changes in the composition and diversity of gut microbiota, known as dysbiosis, is associated with cardiovascular diseases, such as atherosclerosis, hypertension, and heart failure. RECENT FINDINGS: Although recent advances in biochemical and molecular analyses have contributed to the detection, identification, and characterization of a variety of gut microbiota genomes and their associated metabolites, the exact mechanisms of action remain unclear. As the prevalence of cardiovascular disease continues to rise, investigating the gut microbiome as a potential strategy for clinical intervention is highly warranted. SUMMARY: In this review, we discuss correlations between the gut microbiome and heart failure, as well as the effects of altering the microbiome as a potential therapeutic target in cardiovascular diseases including heart failure.


Assuntos
Microbioma Gastrointestinal , Insuficiência Cardíaca , Hipertensão , Disbiose , Insuficiência Cardíaca/microbiologia , Humanos , Hipertensão/microbiologia
19.
Nutrients ; 10(9)2018 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-30142973

RESUMO

Emerging data indicate a correlation between gut microbial composition and cardiovascular disease including hypertension. The host's diet greatly affects microbial composition and metabolite production. Short chain fatty acids (SCFAs) are products of microbial fermentation, which can be utilized by the host. It has been suggested that SCFAs play a pivotal role as mediators in a microbiome host: microbial interactions occur in health and disease. The aim of this study was to evaluate the effect of a high salt diet (HSD) on microbial variation and to determine whether this effect is accompanied by an alteration in fecal SCFAs. To this end, Dahl salt-sensitive rats were divided into two groups (n = 10 each): (A) Control: fed regular chow; and (B) Fed HSD. High-throughput pyrosequencing of the 16S rRNA amplicon sequencing was used for microbiome characterizing. Chromatography-mass spectrometry was used to measure the levels of SCFAs: acetic acid, propionic acid, butyric acid, and isobutyric acid in fecal samples. Differences in microbial composition were noted between groups. Principal Coordinate Analysis (PCoA) principal coordinate 1 (PC1) primarily separated controls from the HSD. Four taxa displayed significant differences between HSD and controls. Taxa from the Erwinia genus, the Christensenellaceae and Corynebacteriaceae families, displayed an increased abundance in HSD versus control. In contrast, taxa from the Anaerostipes genus displayed a decreased abundance in HSD. We were able to identify seven unique taxa that were significantly associated with blood pressure. There was a significant difference in fecal acetic acid, as well as propionic and isobutyric acid, but not in the butyric acid composition between groups. Adding salt to a diet impacts the gut's microbial composition, which may alter fecal SCFA production.


Assuntos
Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal , Hipertensão/microbiologia , Cloreto de Sódio na Dieta/administração & dosagem , Ácido Acético/análise , Actinomycetales/isolamento & purificação , Animais , Pressão Sanguínea , Ácido Butírico/análise , Clostridiales/isolamento & purificação , Dieta , Erwinia/isolamento & purificação , Fezes/química , Hipertensão/metabolismo , Isobutiratos/análise , Masculino , Propionatos/análise , RNA Ribossômico 16S , Ratos , Ratos Endogâmicos Dahl
20.
J Perinatol ; 38(10): 1309-1317, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30068969

RESUMO

BACKGROUND: The potential factors associated with group B streptococcus (GBS) vertical transmission have not been studied in detail. STUDY DESIGN: A prospective cohort study was conducted to recruit 1815 mother-neonate pairs for GBS analysis. Pearson's chi-squared tests and generalized linear models were used to explore the risk factors for neonatal GBS colonization. RESULTS: The rate of GBS vertical transmission was 14.1%. GBS colonization in all neonates was significantly associated with maternal GBS colonization, mode of delivery, episiotomy, number of prenatal vaginal exams, parity, and hypertension. For neonates born to GBS-positive mothers, GBS vertical transmission was associated with the mode of delivery, episiotomy, and sexually transmitted diseases. For neonates born to GBS-negative mothers, neonatal GBS colonization was associated with the number of prenatal vaginal exams, parity, and hypertension. CONCLUSION: These findings suggest the need for prenatal GBS screening for pregnant women and intrapartum antimicrobial prophylaxis for GBS-colonized women.


Assuntos
Hipertensão/epidemiologia , Transmissão Vertical de Doença Infecciosa/estatística & dados numéricos , Complicações Infecciosas na Gravidez/epidemiologia , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/transmissão , Adulto , Antibacterianos/farmacologia , China , Estudos Transversais , Feminino , Humanos , Hipertensão/microbiologia , Recém-Nascido , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Modelos Lineares , Masculino , Gravidez , Complicações Infecciosas na Gravidez/microbiologia , Estudos Prospectivos , Fatores de Risco , Infecções Estreptocócicas/prevenção & controle , Streptococcus agalactiae , Vagina/microbiologia , Adulto Jovem
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