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- Andrikopoulos, Petros, et al.
(author)
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Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide
- 2023
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In: Nature Communications. - 2041-1723 .- 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.
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| 3. |
- Chakaroun, Rima, 1983, et al.
(author)
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The potential of tailoring the gut microbiome to prevent and treat cardiometabolic disease
- 2023
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In: Nature Reviews Cardiology. - : Springer Science and Business Media LLC. - 1759-5002 .- 1759-5010. ; 20:4, s. 217-235
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Journal article (peer-reviewed)abstract
- In this Review, Backhed and colleagues summarize the evidence for gut microbiome alterations in cardiometabolic and cardiovascular diseases and the rationale and potential benefit motivating translational approaches to target the gut microbiota and its metabolites for prevention and treatment. Despite milestones in preventive measures and treatment, cardiovascular disease (CVD) remains associated with a high burden of morbidity and mortality. The protracted nature of the development and progression of CVD motivates the identification of early and complementary targets that might explain and alleviate any residual risk in treated patients. The gut microbiota has emerged as a sentinel between our inner milieu and outer environment and relays a modified risk associated with these factors to the host. Accordingly, numerous mechanistic studies in animal models support a causal role of the gut microbiome in CVD via specific microbial or shared microbiota-host metabolites and have identified converging mammalian targets for these signals. Similarly, large-scale cohort studies have repeatedly reported perturbations of the gut microbial community in CVD, supporting the translational potential of targeting this ecological niche, but the move from bench to bedside has not been smooth. In this Review, we provide an overview of the current evidence on the interconnectedness of the gut microbiome and CVD against the noisy backdrop of highly prevalent confounders in advanced CVD, such as increased metabolic burden and polypharmacy. We further aim to conceptualize the molecular mechanisms at the centre of these associations and identify actionable gut microbiome-based targets, while contextualizing the current knowledge within the clinical scenario and emphasizing the limitations of the field that need to be overcome.
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| 4. |
- Molinaro, Antonio, et al.
(author)
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Microbially Produced Imidazole Propionate Is Associated With Heart Failure and Mortality
- 2023
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In: JACC: Heart Failure. - 2213-1779 .- 2213-1787. ; 11:7, s. 810-821
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Journal article (peer-reviewed)abstract
- Background: Over the past years, it has become clear that the microbial ecosystem in the gut has a profound capacity to interact with the host through the production of a wide range of bioactive metabolites. The microbially produced metabolite imidazole propionate (ImP) is clinically and mechanistically linked with insulin resistance and type 2 diabetes, but it is unclear how ImP is associated with heart failure. Objectives: The authors aimed to explore whether ImP is associated with heart failure and mortality. Methods: ImP serum measurements in 2 large and independent clinical cohorts of patients (European [n = 1,985] and North American [n = 2,155]) with a range of severity of cardiovascular disease including heart failure. Univariate and multivariate Cox regression analyses were performed to delineate the impact of ImP on 5-year mortality in the North American cohort, independent of other covariates. Results: ImP is independently associated with reduced ejection fraction and heart failure in both cohorts, even after adjusting for traditional risk factors. Elevated ImP was a significant independent predictor of 5-year mortality (for the highest quartile, adjusted HR: 1.85 [95% CI: 1.20-2.88]; P < 0.01). Conclusions: The gut microbial metabolite ImP is increased in individuals with heart failure and is a predictor of overall survival.
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| 5. |
- Schamarek, I., et al.
(author)
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The role of the oral microbiome in obesity and metabolic disease: potential systemic implications and effects on taste perception
- 2023
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In: Nutrition Journal. ; 22:1
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Journal article (peer-reviewed)abstract
- Obesity and its metabolic sequelae still comprise a challenge when it comes to understanding mechanisms, which drive these pandemic diseases. The human microbiome as a potential key player has attracted the attention of broader research for the past decade. Most of it focused on the gut microbiome while the oral microbiome has received less attention. As the second largest niche, the oral microbiome is associated with a multitude of mechanisms, which are potentially involved in the complex etiology of obesity and associated metabolic diseases. These mechanisms include local effects of oral bacteria on taste perception and subsequent food preference as well as systemic effects on adipose tissue function, the gut microbiome and systemic inflammation. This review summarizes a growing body of research, pointing towards a more prominent role of the oral microbiome in obesity and associated metabolic diseases than expected. Ultimately, our knowledge on the oral microbiome may support the development of new patient oriented therapeutic approaches inevitable to relieve the health burden of metabolic diseases and to reach long-term benefits in patients ' lives.
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