Potassium Alginate Oligosaccharides Alter Gut Microbiota, and Have Potential to Prevent the Development of Hypertension and Heart Failure in Spontaneously Hypertensive Rats.

Food-derived oligosaccharides show promising therapeutic potential in lowering blood pressure (BP), but the mechanism is poorly understood. Recently, the potential role of gut microbiota (GM) in hypertension has been investigated, but the specific GM signature that may participate in hypertension remains unclear. To test the potassium alginate oligosaccharides (PAO) mechanism in lowering BP and specific microbial signature changes in altering GM, we administered various dosages of PAO in 40 spontaneously hypertensive rats for a duration of six weeks. We analyzed BP, sequenced the 16S ribosomal DNA gene in the cecum content, and gathered RNA-seq data in cardiac tissues. We showed that the oral administration of PAO could significantly decrease systolic BP and mean arterial pressure. Transcriptome analyses demonstrated that the protective effects of developing heart failure were accompanied by down-regulating of the Natriuretic Peptide A gene expression and by decreasing the concentrations of angiotensin II and atrial natriuretic peptide in plasma. In comparison to the Vehicle control, PAO could increase the microbial diversity by altering the composition of GM. PAO could also decrease the ratio of Firmicutes to Bacteroidetes by decreasing the abundance of Prevotella and Phascolarctobacterium bacteria. The favorable effect of PAO may be added to the positive influence of the abundance of major metabolites produced by Gram-negative bacteria in GM. We suggest that PAO caused changes in GM, and thus, they played an important role in preventing the development of cardiovascular disease.

The Gut Microbiome of Heart Failure With Preserved Ejection Fraction.

Background Risk factors for heart failure with preserved ejection fraction (HFpEF) include hypertension, age, sex, and obesity. Emerging evidence suggests that the gut microbiota independently contributes to each one of these risk factors, potentially mediated via gut microbial-derived metabolites such as short-chain fatty acids. In this study, we determined whether the gut microbiota were associated with HFpEF and its risk factors. Methods and Results We recruited 26 patients with HFpEF and 67 control participants from 2 independent communities. Patients with HFpEF were diagnosed by exercise right heart catheterization. We assessed the gut microbiome by bacterial 16S rRNA sequencing and food intake by the food frequency questionnaire. There was a significant difference in α-diversity (eg, number of microbes) and ß-diversity (eg, type and abundance of microbes) between both cohorts of controls and patients with HFpEF (P=0.001). We did not find an association between ß-diversity and specific demographic or hemodynamic parameters or risk factors for HFpEF. The Firmicutes to Bacteroidetes ratio, a commonly used marker of gut dysbiosis, was lower, but not significantly so (P=0.093), in the patients with HFpEF. Compared with controls, the gut microbiome of patients with HFpEF was depleted of bacteria that are short-chain fatty acid producers. Consistent with this, participants with HFpEF consumed less dietary fiber (17.6±7.7 versus 23.2±8.8 g/day; P=0.016). Conclusions We demonstrate key changes in the gut microbiota in patients with HFpEF, including the depletion of bacteria that generate metabolites known to be important for cardiovascular homeostasis. Further studies are required to validate the role of these gut microbiota and metabolites in the pathophysiology of HFpEF.

Rifaximin or Saccharomyces boulardii in heart failure with reduced ejection fraction: Results from the randomized GutHeart trial.

BACKGROUND: The gut microbiota represents a potential treatment target in heart failure (HF) through microbial metabolites such as trimethylamine N-oxide (TMAO) and systemic inflammation. Treatment with the probiotic yeast Saccharomyces boulardii have been suggested to improve left ventricular ejection fraction (LVEF). METHODS: In a multicentre, prospective randomized open label, blinded end-point trial, we randomized patients with LVEF <40% and New York Heart Association functional class II or III, despite optimal medical therapy, to treatment (1:1:1) with the probiotic yeast Saccharomyces boulardii, the antibiotic rifaximin, or standard of care (SoC) only. The primary endpoint, the baseline-adjusted LVEF at three months, was assessed in an intention-to-treat analysis. FINDINGS: We enrolled a total of 151 patients. After three months' treatment, the LVEF did not differ significantly between the SoC arm and the rifaximin arm (mean difference was -1•2 percentage points; 95% CI -3•2 - 0•7; p=0•22) or between the SoC arm and the Saccharomyces boulardii arm (mean difference -0•2 percentage points; 95% CI -2•2 - 1•9; p=0•87). We observed no significant between-group differences in changes in microbiota diversity, TMAO, or C-reactive protein. INTERPRETATION: Three months' treatment with Saccharomyces boulardii or rifaximin on top of SoC had no significant effect on LVEF, microbiota diversity, or the measured biomarkers in our population with HF. FUNDING: The trial was funded by the Norwegian Association for Public Health, the Blix foundation, Stein Erik Hagen's Foundation for Clinical Heart Research, Ada og Hagbart Waages humanitære og veldedige stiftelse, Alfasigma, and Biocodex.

Changes of gut microbiome composition and metabolites associated with hypertensive heart failure rats.

BACKGROUND: The potential role of the gut microbiome (GM) in heart failure (HF) had recently been revealed. However, the underlying mechanisms of the GM and fecal metabolome in HF have not been characterized. The Dahl salt-sensitive rat model of hypertensive heart failure (H-HF) was used to study the clinical symptoms and characteristics. To elucidate the pathogenesis of HF, we combined 16S rRNA gene sequencing and metabolomics to analyze gut microbial compositions and fecal metabolomic profiles of rats with H-HF. RESULTS: PCoA of beta diversity shown that the gut microbiome composition profiles among the three groups were separated. Gut microbial composition was significantly altered in H-HF rats, the ratio of Firmicutes to Bacteroidetes(F/B) increased and the abundance of Muribaculaceae, Lachnospiraceae, and Lactobacillaceae decreased. Significantly altered levels of 17 genera and 35 metabolites were identified as the potential biomarker of H-HF. Correlation analysis revealed that specific altered genera were strongly correlated with changed fecal metabolites. The reduction in short-chain fatty acids (SCFA)-producing bacteria and trimethylamine N-oxide (TMAO) might be a notable characteristic for H-HF. CONCLUSIONS: This is the first study to characterize the fecal microbiome of hypertensive heart failure by integrating 16S rRNA gene sequencing and LC-MS-based metabolomics approaches. Collectively, the results suggesting changes of gut microbiome composition and metabolites are associated with hypertensive heart failure rats.

Bacterial metabolites trimethylamine N-oxide and butyrate as surrogates of small intestinal bacterial overgrowth in patients with a recent decompensated heart failure.

In patients with heart failure (HF), the exhaled concentrations of hydrogen after a breath test-a non-invasive assessment of small intestinal overgrowth- has been related to HF severity and higher risk of adverse outcomes. Indeed, two intestinal bacterial metabolites-blood Trimethylamine N-Oxide (TMAO) and butyrate-have been related to a worse prognosis in HF. However, the relationship between the exhaled concentrations of hydrogen after a breath test and these two metabolites remains unknown. Thus, in this post-hoc analysis, we sought to evaluate whether these two metabolites are associated with the exhaled concentrations of hydrogen after a breath test in patients with a recent admission for HF. We included 60 patients with a recent hospitalization for HF. Cumulative hydrogen over time was integrated into a single measurement by the area under the concentration curve (AUC-H2). A linear regression multivariable analysis was used to evaluate the associations. A 2-sided p-value < 0.05 was considered to be statistically significant. The median (p25-p75) amino-terminal pro-brain natriuretic peptide, AUC-H2, TMAO, and Butyrate were 4789 pg/ml (1956-11149), 1615 (700-2585), 0.68 (0.42-1.12), and 0.22 ± 13, respectively. After multivariate adjustment, TMAO and butyrate were significantly associated with AUC-H2 (p = 0.027 and p = 0.009, respectively). For TMAO, this association was positive and for butyrate, negative. Bacterial-origin metabolites TMAO and Butyrate were independently related to AUC-H2 in patients with a recent hospitalization for acute HF.

Association of Small Intestinal Bacterial Overgrowth With Heart Failure and Its Prediction for Short-Term Outcomes.

Background Small intestinal bacterial overgrowth (SIBO) is a common pathological condition of intestinal microbiota. The prevalence of SIBO and its prognostic value in patients with heart failure (HF) are unknown. Methods and Results A total of 287 patients tested for SIBO using lactulose hydrogen-methane breath test were evaluated. At least 1 of the following criteria fulfilled was SIBO positive: patients with fasting hydrogen level ≥20 parts per million (ppm) or a ≥20 ppm rise in hydrogen by 90 minutes were diagnosed with SIBO (H2) positive; and patients with methane levels ≥10 ppm at any test point were diagnosed with SIBO (CH4) positive. The association between SIBO and the composite of cardiovascular death and HF rehospitalization was investigated. In 287 consecutive patients with HF, 128 (45%) were positive for SIBO. Our result showed SIBO increased the risk of HF rehospitalization in patients with HF with reduced ejection fraction (P<0.001), and the risk of cardiovascular death in patients with HF with preserved EF (P=0.011). SIBO was an independent risk factor of primary end point in patients with HF (hazard ratio [HR], 2.13; 95% CI; 1.26-3.58; P=0.005). In addition, SIBO (CH4) showed a prognostic value on adverse outcomes (HR, 2.35; 95% CI, 1.38-4.02; P<0.001), whereas the association between SIBO (H2) and outcomes was not statistically significant. Conclusions There was high prevalence of SIBO in patients with HF, and SIBO was independently associated with poor outcomes. Proactive treatment for SIBO may provide extra benefit for patients with HF.

The role of diet-derived short-chain fatty acids in regulating cardiac pressure overload.

Heart failure (HF) is one of the leading causes of mortality and morbidity in the modern world whose increasing prevalence is associated with "Western" diet and sedentary lifestyles. Of particular concern is the increasing burden of HF with preserved ejection fraction (HFpEF) that involves complex pathophysiology and is difficult to treat. Pressure overload caused by hypertension (HTN) is the predominant driver of cardiac injury, left ventricular hypertrophy, and fibrosis that progresses to diastolic dysfunction and ultimately HFpEF. Although pharmacological control of blood pressure may affect the degree of pressure overload, such therapies are largely ineffective in established HFpEF, and there is a need to modulate the festering inflammatory and fibrotic response to injury to halt and perhaps reverse pathology. An emerging literature indicates potentially important links between the gut microbiota, dietary soluble fiber, and microbiota-derived metabolites that modulate blood pressure and the immune response. In particular, high-fiber diets demonstrate protective properties in systemic hypertension and left-sided cardiac pathology, and this action is closely associated with short-chain fatty acid (SCFA)-producing bacteria. Mechanisms underlying the beneficial action of SCFAs in immunity and the systemic circulation could potentially be applied to the treatment of hypertension and the cardiac damage it causes. In this review, we discuss the potential beneficial effects of SCFAs, with an emphasis on mechanisms that are involved in cardiac responses to pressure overload.

Gut microbiome - A potential mediator of pathogenesis in heart failure and its comorbidities: State-of-the-art review.

Gut microbiome (GMB) has been increasingly recognized as a contributor to development and progression of heart failure (HF), immune-mediated subtypes of cardiomyopathy (myocarditis and anthracycline-induced cardiotoxicity), response to certain cardiovascular drugs, and HF-related comorbidities, such as chronic kidney disease, cardiorenal syndrome, insulin resistance, malnutrition, and cardiac cachexia. Gut microbiome is also responsible for the "gut hypothesis" of HF, which explains the adverse effects of gut barrier dysfunction and translocation of GMB on the progression of HF. Furthermore, accumulating evidence has suggested that gut microbial metabolites, including short chain fatty acids, trimethylamine N-oxide (TMAO), amino acid metabolites, and bile acids, are mechanistically linked to pathogenesis of HF, and could, therefore, serve as potential therapeutic targets for HF. Even though there are a variety of proposed therapeutic approaches, such as dietary modifications, prebiotics, probiotics, TMAO synthesis inhibitors, and fecal microbial transplant, targeting GMB in HF is still in its infancy and, indeed, requires further preclinical and clinical evidence. In this review, we aim to highlight the role gut microbiome plays in HF pathophysiology and its potential as a novel therapeutic target in HF.

Manipulation of the gut microbiota by the use of prebiotic fibre does not override a genetic predisposition to heart failure.

Increasing evidence supports a role for the gut microbiota in the development of cardiovascular diseases such as hypertension and its progression to heart failure (HF). Dietary fibre has emerged as a modulator of the gut microbiota, resulting in the release of gut metabolites called short-chain fatty acids (SCFAs), such as acetate. We have shown previously that fibre or acetate can protect against hypertension and heart disease in certain models. HF is also commonly caused by genetic disorders. In this study we investigated whether the intake of fibre or direct supplementation with acetate could attenuate the development of HF in a genetic model of dilated cardiomyopathy (DCM) due to overexpression of the cardiac specific mammalian sterile 20-like kinase (Mst1). Seven-week-old male mice DCM mice and littermate controls (wild-type, C57BL/6) were fed a control diet (with or without supplementation with 200 mM magnesium acetate in drinking water), or a high fibre diet for 7 weeks. We obtained hemodynamic, morphological, flow cytometric and gene expression data. The gut microbiome was characterised by 16S rRNA amplicon sequencing. Fibre intake was associated with a significant shift in the gut microbiome irrespective of mouse genotype. However, neither fibre or supplementation with acetate were able to attenuate cardiac remodelling or cardiomyocyte apoptosis in Mst1 mice. Furthermore, fibre and acetate did not improve echocardiographic or hemodynamic parameters in DCM mice. These data suggest that although fibre modulates the gut microbiome, neither fibre nor acetate can override a strong genetic contribution to the development of heart failure in the Mst1 model.

Circadian influence on the microbiome improves heart failure outcomes.

Myocardial infarction (MI) leading to heart failure (HF) is a major cause of death worldwide. Previous studies revealed that the circadian system markedly impacts cardiac repair post-MI, and that light is an important environmental factor modulating the circadian influence over healing. Recent studies suggest that gut physiology also affects the circadian system, but how it contributes to cardiac repair post-MI and in HF is not well understood. To address this question, we first used a murine coronary artery ligation MI model to reveal that an intact gut microbiome is important for cardiac repair. Specifically, gut microbiome disruption impairs normal inflammatory responses in infarcted myocardium, elevates adverse cardiac gene biomarkers, and leads to worse HF outcomes. Conversely, reconstituting the microbiome post-MI in mice with prior gut microbiome disruption improves healing, consistent with the notion that normal gut physiology contributes to cardiac repair. To investigate a role for the circadian system, we initially utilized circadian mutant Clock∆19/∆19 mice, revealing that a functional circadian mechanism is necessary for gut microbiome benefits on post-MI cardiac repair and HF. Finally, we demonstrate that circadian-mediated gut responses that benefit cardiac repair can be conferred by time-restricted feeding, as wake time feeding of MI mice improves HF outcomes, but these benefits are not observed in MI mice fed during their sleep time. In summary, gut physiology is important for cardiac repair, and the circadian system influences the beneficial gut responses to improve post-MI and HF outcomes.

Gut Microbiota Profile Identifies Transition From Compensated Cardiac Hypertrophy to Heart Failure in Hypertensive Rats.

Microcirculatory alterations displayed by patients with heart failure (HF) induce structural and functional intestinal changes that may affect normal gut microbial community. At the same time, gut microbiota can influence pathological mechanisms implicated in HF progression. However, it is unknown whether gut microbiota dysbiosis can precede the development of cardiac alterations in HF or it is only a mere consequence. Our aim was to investigate the potential relationship between gut microbiota composition and HF development by comparing spontaneously hypertensive heart failure and spontaneously hypertensive rat models. Gut microbiota from spontaneously hypertensive heart failure, spontaneously hypertensive rat, and normotensive Wistar Kyoto rats at 9 and 19 months of age was analyzed by sequencing the 16S ribosomal RNA gene, and KEGG metabolic pathways associated to 16S profiles were predicted. Beta diversity, Firmicutes/Bacteroidetes ratio, taxonomic abundances, and potential metabolic functions of gut microbiota were significantly different in spontaneously hypertensive heart failure with respect to spontaneously hypertensive rat before (9 months) and after (19 months) cardiac differences were presented. Nine-month-old spontaneously hypertensive heart failure showed a significant increase in the genera Paraprevotella, Oscillospira, Prevotella 9, Faecalitalea, Faecalibacterium, Ruminiclostridium 6, Phascolarctobacterium, Butyrivibrio, Parasutterella, and Parabacteroides compared with both Wistar Kyoto and spontaneously hypertensive rat, while Ruminiclostridium 9, Oscillibacter, Ruminiclostridium, Mucispirillum, Intestinimonas, and Akkermansia were diminished. Of them, Akkermansia, Prevotella 9, Paraprevotella, and Phascolarctobaterium were associated to changes in cardiac structure and function. Our results demonstrate an association between specific changes in gut microbiota and the development of HF in a hypertensive model of HF and further support the intervention to restore gut microbiota as an innovative therapeutic strategy for preventing HF.

The gut microbiome in dogs with congestive heart failure: a pilot study.

Compromised gut health and dysbiosis in people with heart failure has received a great deal of attention over the last decade. Whether dogs with heart failure have a similar dysbiosis pattern to what is described in people is currently unknown. We hypothesised that dogs with congestive heart failure have quantifiable dysbiosis compared to healthy dogs that are similar in sex and age. A total of 50 dogs (15 healthy dogs and 35 dogs with congestive heart failure) were prospectively recruited, and their faecal gut microbiome was assessed using 16S rRNA sequencing (Illumina MiSeq platform). There was no significant change in the microbial diversity and richness in dogs with congestive heart failure. However, there was an increase in abundance of Proteobacteria in the congestive heart failure group (p = 0.014), particularly due to an increase in the family Enterobacteriaceae (p = 0.002) and Escherichia coli (p = 0.033). We conclude that dogs with congestive heart failure have dysbiosis, and we show additional trends in our data suggesting that dogs may have a similar pattern to that described in people. The results of this study provide useful preliminary information and raise the possibility that dogs represent a clinically relevant animal model of dysbiosis in people with heart failure.

Heart Failure Disturbs Gut-Blood Barrier and Increases Plasma Trimethylamine, a Toxic Bacterial Metabolite.

Trimethylamine (TMA) is a gut bacteria product oxidized by the liver to trimethylamine-N-oxide (TMAO). Clinical evidence suggests that cardiovascular disease is associated with increased plasma TMAO. However, little headway has been made in understanding this relationship on a mechanistic and molecular level. We investigated the mechanisms affecting plasma levels of TMAO in Spontaneously Hypertensive Heart Failure (SHHF) rats. Healthy Wistar Kyoto (WKY) and SHHF rats underwent metabolic, hemodynamic, histopathological and biochemical measurements, including tight junction proteins analysis. Stool, plasma and urine samples were evaluated for TMA and TMAO using ultra performance liquid chromatography-mass spectrometry. SHHF presented disturbances of the gut-blood barrier including reduced intestinal blood flow, decreased thickness of the colonic mucosa and alterations in tight junctions, such as claudin 1 and 3, and zonula occludens-1. This was associated with significantly higher plasma levels of TMA and TMAO and increased gut-to-blood penetration of TMA in SHHF compared to WKY. There was no difference in kidney function or liver oxidation of TMA to TMAO between WKY and SHHF. In conclusion, increased plasma TMAO in heart failure rats results from a perturbed gut-blood barrier and increased gut-to-blood passage of TMAO precursor, i.e., TMA. Increased gut-to-blood penetration of bacterial metabolites may be a marker and a mediator of cardiovascular pathology.

Nonlethal Inhibition of Gut Microbial Trimethylamine N-oxide Production Improves Cardiac Function and Remodeling in a Murine Model of Heart Failure.

Background Patients at increased risk for coronary artery disease and adverse prognosis during heart failure exhibit increased levels of circulating trimethylamine N-oxide (TMAO), a metabolite formed in the metabolism of dietary phosphatidylcholine. We investigated the efficacy of dietary withdrawal of TMAO as well as use of a gut microbe-targeted inhibitor of TMAO production, on cardiac function and structure during heart failure. Methods and Results Male C57BLK/6J mice were fed either control diet, a diet containing TMAO (0.12% wt/wt), a diet containing choline (1% wt/wt), or a diet containing choline (1% wt/wt) plus a microbial choline trimethylamine lyase inhibitor, iodomethylcholine (0.06% wt/wt), starting 3 weeks before transverse aortic constriction. At 6 weeks after transverse aortic constriction, a subset of animals in the TMAO group were switched to a control diet for the remainder of the study. Left ventricular structure and function were monitored at 3-week intervals. Withdrawal of TMAO from the diet attenuated adverse ventricular remodeling and improved cardiac function compared with the TMAO group. Similarly, inhibiting gut microbial conversion of choline to TMAO with a choline trimethylamine lyase inhibitor, iodomethylcholine, improved remodeling and cardiac function compared with the choline-fed group. Conclusions These experimental findings are clinically relevant, and they demonstrate that TMAO levels are modifiable following long-term exposure periods with either dietary withdrawal of TMAO or gut microbial blockade of TMAO generation. Furthermore, these therapeutic strategies to reduce circulating TMAO levels mitigate the negative effects of dietary choline and TMAO in heart failure.

Effect of Prebiotic Complex on Gut Microbiota and Endotoxemia in Female Rats with Modeled Heart Failure.

We studied the levels endotoxin and microbial markers in the blood of female rats with experimental heart failure and the effects of preliminary treatment with a prebiotic complex based on fermented wheat bran and inactivated Saccharomyces cerevisiae culture on these parameters. The concentrations of endotoxin, markers of lactobacilli, and opportunistic microorganisms were found to increase in rats with experimental heart failure and significantly decreased against the background of treatment with prebiotic complex. The dynamics of markers of bifidobacteria, eubacteria, and propionibacteria were reciprocal. The observed effect of the prebiotic complex effect on gut microbiota in rats with experimental heart failure suggests that this complex can be used for the correction of intestinal dysbiosis and endotoxemia in this clinical condition.

Association with Controlling Nutritional Status (CONUT) Score and In-hospital Mortality and Infection in Acute Heart Failure.

The high controlling nutritional status (CONUT) score that represents poor nutritional status has been acknowledged to have prognostic implications in chronic heart failure. We aimed to investigate its role in acute decompensated heart failure (ADHF). Using the data from an multicenter registry that enrolled 4056 consecutive patients hospitalized for ADHF in Japan between 2014 and 2016, we analyzed 2466 patients in whom data on the components of the CONUT score at hospital presentation were available. The decrease of lymphocyte count and total cholesterol was assigned with 0, 1, 2, and 3 points and the decrease of albumin was assigned with 0, 2, 4, and 6 points according to the severity. We defined low CONUT score as 0-4 (N = 1568) and high CONUT score as 5-9 (N = 898). The patients in the high CONUT score group were older and more likely to have a smaller body mass index than those in the low CONUT score group. The high CONUT score group was associated with higher rate of death and infection during the index hospitalization compared to the low CONUT score group (9.0% versus 4.4%, and 21.9% versus 12.7%, respectively). After adjusting for confounders, the excess risk of high relative to low CONUT score for mortality and infection was significant (OR: 1.61, 95%CI: 1.05-2.44, and OR: 1.66, 95%CI: 1.30-2.12, respectively). The effect was incremental according to the score. High CONUT score was associated with higher risk for in-hospital mortality and infection in an incremental manner in patients hospitalized for ADHF.

Minimum inhibitory concentration changes in relapsed left ventricular assist device driveline infections.

Driveline infection is the most common infectious complication in patients with left ventricular assist devices. Minimum inhibitory concentration changes are not well described in relapsed driveline infections. This retrospective descriptive epidemiology study of patients with left ventricular assist device implantation between January 1, 2013, and August 1, 2017, who developed driveline infection with positive cultures aimed to describe minimum inhibitory concentration changes. Of the 330 patients underwent left ventricular assist device implantation, 30 (9%) met criteria for driveline infection. Median duration of follow-up was 26 months (interquartile range 16, 39) and time to first driveline infection was 171 days (interquartile range 83, 403). There were 74 driveline infections: 40 new and 34 relapsed. Staphylococcus aureus was most common in new and relapsed driveline infection. Thirteen patients comprised the 34 relapsed infections, 9 of which experienced a minimum inhibitory concentration change. Median time to first minimum inhibitory concentration change was 56 days (interquartile range 36-88), and type of minimum inhibitory concentration change was an increase in five cases, decrease in two cases, and both increase and decrease in two cases. Minimum inhibitory concentration changes did not result in resistance in S. aureus but did in Pseudomonas aeruginosa and Mycobacterium fortuitum relapsed driveline infection. Time to first relapse from initial infection was longer in those who received suppressive therapy, 60 days versus 83 days, p = 0.047. Relapsed driveline infections were most common with S. aureus. Minimum inhibitory concentration changes were quite variable and may not be the major contributor to relapsed infection in gram-positive driveline infection.

Role and Effective Therapeutic Target of Gut Microbiota in Heart Failure.

Although the mechanism of the occurrence and development of heart failure has been continuously explored in the past ten years, the mortality and readmission rate of heart failure is still very high. Modern studies have shown that gut microbiota is associated with a variety of cardiovascular diseases, among which the study of gut microbiota and heart failure attracts particular attention. Therefore, understanding the role of gut microbiota in the occurrence and development of heart failure will help us further understand the pathogenesis of heart failure and provide new ideas for its treatment. This paper introduced intestinal flora and its metabolites, summarized the changes of intestinal flora in patients with heart failure, clarified that intestinal barrier damage and bacterial translocation induced inflammation and immune response aggravated heart failure, and altered intestinal microflora affected various metabolic pathways including trimethylamine/TMAO, SCFA, and Bile acid pathway leads to heart failure. At the same time, regulating intestinal microflora through diet, probiotics, antibiotics, fecal transplantation and microbial enzyme inhibitors has grown up to be a potential treatment for many metabolic disorders.

Another Whipple's triad? Pericardial, myocardial and valvular disease in an unusual case presentation from a Canadian perspective.

BACKGROUND: Whipple's disease is a clinically relevant multi-system disorder that is often undiagnosed given its elusive nature. We present an atypical case of Whipple's disease involving pan-valvular endocarditis and constrictive pericarditis, requiring cardiac intervention. A literature review was also performed assessing the prevalence of atypical cases of Whipple's disease. CASE PRESENTATION: A previously healthy 56-year-old male presented with a four-year history of congestive heart failure with weight loss and fatigue. Notably, he had absent gastrointestinal symptoms. He went on to develop pan-valvular endocarditis and constrictive pericarditis requiring urgent cardiac surgery. A clinical diagnosis of Whipple's disease was suspected, prompting duodenal biopsy sampling which was unremarkable, Subsequently, Tropheryma whipplei was identified by 16S rDNA PCR on the cardiac valvular tissue. He underwent prolonged antibiotic therapy with recovery of symptoms. CONCLUSIONS: Our study reports the first known case of Whipple's disease involving pan-valvular endocarditis and constrictive pericarditis. A literature review also highlights this presentation of atypical Whipple's with limited gastrointestinal manifestations. Duodenal involvement was limited and the gold standard of biopsy was not contributory. We also highlight the Canadian epidemiology of the disease from 2012 to 2016 with an approximate 4% prevalence rate amongst submitted samples. Routine investigations for Whipple's disease, including duodenal biopsy, in this case may have missed the diagnosis. A high degree of suspicion was critical for diagnosis of unusual manifestations of Whipple's disease.

The gut microbiome and heart failure: A better gut for a better heart.

Despite the development of new drugs and therapeutic strategies, mortality and morbidity related to heart failure (HF) remains high. It is also the leading cause of global mortality. Several concepts have been proposed to explore the underlying pathogenesis of HF, but there is still a strong need for more specific and complementary therapeutic options. In recent years, accumulating evidence has demonstrated that changes in the composition of gut microbiota, referred to as dysbiosis, might play a pivotal role in the development of several diseases, including HF. HF-associated decreased cardiac output, resulting in bowell wall oedema and intestine ischaemia, can alter gut structure, peamibility and function. These changes would favour bacterial translocation, exacerbating HF pathogenesis at least partly through activation of systemic inflammation. Although our knowledge of the precise molecular mechanisms by which gut dysbiosis influance HF is still limited, a growing body of evidence has recently demonstrated the impact of a series of gut microbiome-derived metabolites, such as trimetylamine N-oxide, short-chain fatty acids or secondary bile acids, which have been shown to play critical roles in cardiac health and disease. This review will summarize the role of gut microbiota and its metabolites in the pathogenesis of HF. Current and future preventive and therapeutic strategies to prevent HF by an adequate modulation of the microbiome and its derived metabolites are also discussed.