Design of the GutHeart—targeting gut microbiota to treat heart failure—trial: a Phase II, randomized clinical trial

Mayerhofer, Christiane Caroline; Awoyemi, Ayodeji; Moscavitch, Samuel Datum; Lappegård, Knut Tore; Hov, Johannes Espolin Roksund; Aukrust, Pål; Hovland, Anders; Lorenzo, Andréa Rocha de; Halvorsen, Sigrun; Seljeflot, Ingebjørg; Gullestad, Lars; Trøseid, Marius; Broch, Kaspar

doi:10.1002/ehf2.12332

Cited by 42 publications

(29 citation statements)

References 28 publications

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“…103 Preliminary results from another ongoing RCT showed that brady yeast can increase LVEF by 5% in patients with systolic HF, and the final results are expected to be achieved in 2020. 104 In conclusion, although studies of probiotics in HF patients remain scarce, this treatment strategy has a great prospect.…”

Section: Gutàtmaoàhf Axis As a Potential Therapeutic Target For Hfmentioning

confidence: 99%

TMAO: how gut microbiota contributes to heart failure

Zhang

Wang

et al. 2021

Translational Research

150

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An increasing amount of evidence reveals that the gut microbiota is involved in the pathogenesis and progression of various cardiovascular diseases. In patients with heart failure (HF), splanchnic hypoperfusion causes ischemia and intestinal edema, allowing bacterial translocation and bacterial metabolites to enter the blood circulation via an impaired intestinal barrier. This results in local and systemic inflammatory responses. Gut microbe-derived metabolites are implicated in the pathology of multiple diseases, including HF. These landmark findings suggest that gut microbiota influences the host's metabolic health, either directly or indirectly by producing several metabolites. In this review, we mainly discuss a newly identified gut microbiota-dependent metabolite, trimethylamine N-oxide (TMAO), which appears to participate in the pathologic processes of HF and can serve as an early warning marker to identify individuals who are at the risk of disease progression. We also discuss the potential of the gutÀTMAOÀHF axis as a new target for HF treatment and highlight the current controversies and potentially new and exciting directions for future research.

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Section: Gutàtmaoàhf Axis As a Potential Therapeutic Target For Hfmentioning

confidence: 99%

TMAO: how gut microbiota contributes to heart failure

Zhang

Wang

et al. 2021

Translational Research

150

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“…Probiotics have been around for some time now and while they have shown marginal benefit in attenuating myocardial hypertrophy in animal studies, and were associated with left ventricular ejection fraction improvement in one small study, clinical evidence of their benefit in HF is still largely lacking. The ongoing GutHeart study (antibiotic rifaximin vs. the probiotic yeast Saccharomyces boulardii vs. no treatment) will likely shed more light on the role of probiotics and antibiotics in HF . Fecal transplantation on the other hand has had modest success in treating gut dysbiosis, but has significant variability in patient response and carries the potential risk of transmitting harmful infections to the new host .…”

Section: Challenges and Solutions To The Gut Dysbiosis Theorymentioning

confidence: 99%

Gut dysbiosis and heart failure: navigating the universe within

Madan

Mehra

2020

European J of Heart Fail

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Alternations in gut microbial composition (i.e. loss of microbial diversity or ‘gut dysbiosis’) have been associated with heart failure with reduced ejection fraction (HFrEF). It has also been suggested that increased chronic low‐level inflammation and immune system dysregulation seen in patients with HFrEF could be related to gut dysbiosis and increased intestinal permeability. Hence, the concept of modulating gut microbial composition with the goal of reducing systemic inflammation and controlling HFrEF progression has generated a substantial interest in the scientific community. However, several challenges to the gut dysbiosis theory remain as the exact gut microbial composition in HFrEF patients in these studies is not the same and a common microbiome linked to HFrEF is not yet established. With the advances in culture independent sequencing techniques it has also become evident that the gut microbiome may be much more diverse than previously believed. Further, various ‘omic’ technologies have enabled us to appreciate the potential role of gut microbial metabolites in various physiological processes in the host. Hence, identification of specific gut microbial metabolites may offer an alternative approach at solving this gut microbiome‐HFrEF puzzle. In the current review, we evaluate the concept of gut symbiosis, the potential role of gut dysbiosis in systemic inflammation and HFrEF, and finally highlight the challenges faced by the gut dysbiosis theory in HFrEF and provide a framework for the possible solutions.

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“…We thank Chun Liang and colleagues for their comments on the design of the GutHeart trial, but disagree with their assertations regarding the potential risk associated with direct modulation of the gut flora. The authors refer to a recent study in which 28 patients with brain fogginess were compared with eight patients without brain fogginess .…”

mentioning

confidence: 98%