Petra Mamic, MD, is a cardiologist and member of the Cardiovascular Institute at Stanford University.

Petra Mamic, MD

Possible Correlation Between Gut Microbiome and Heart Failure With Petra Mamic, MD

The gut microbiome has the potential to become both a biomarker and a potential therapy pathway for 

Heart Failure Society of America (HFSA) Annual Scientific Meeting 2025

Presented by Petra Mamic, MD, a cardiologist and member of the Cardiovascular Institute at Stanford University, these data, while still in their infancy, highlight yet another potential multidisciplinary approach for HF. Prior animal trials, in vitro experiments, and ongoing human studies are providing further positive data to this end.

 editorial team spoke with Mamic at the conference, discussing her presentation and the possible next steps for this groundbreaking potential therapy.

“If we can improve our understanding of the gut microbiome, we can develop novel biomarkers for patients with chronic heart failure, diagnostic and prognostic biomarkers,” Mamic told 

. “We can improve the way we risk stratify our patients.”

Mamic has headed several prior studies both documenting and investigating this connection; in 2022, she and colleagues posited the “gut hypothesis” of HF. This highlights the acutely adaptive but chronically maladaptive hemodynamic, pro-inflammatory, and neurohumoral responses, which are both caused and influence the gut microbiome. Additionally, gut ischemia develops in HF due to elevated gut venous pressures and decreased blood flow in the splanchnic arteries.

The investigators went on to note that endotoxin, of which the gut is the primary source, triggers systemic production of pro-inflammatory cytokines, which negatively impact cardiomyocyte functions, cause endothelial dysfunction, and impair peripheral blood flow. Additionally, it directly impairs cardiac function by inducing intracardiac inflammatory responses, which decreases cardiac contractility.

The team also implicates bile acids, amino acid metabolites, and trimethylamine N-oxide as having a substantial effect on both HF and cardiovascular physiology at large. They play roles in fat absorption, cholesterol, lipid and glucose metabolism, and in some cases, direct effects on cardiac function and vascular tone. This further represents the potential linkage between the 2 conditions.

In another study from 2023, Mamic and colleagues highlight evidence implicating microbiome dysregulation in HF initiation, progression and treatment responses. They note the function of the gut as a barrier protecting from pathogen invasion. In chronic HF, the gut barrier is compromised, resulting in abnormal gut permeability. The resulting infiltration of microbes and their products, stimulating the immune and inflammatory responses, may act as a primary driver for chronic low-grade inflammation in chronic HF.

Given these connections, Mamic and colleagues posited another connection between the gut and systemic inflammation at earlier stages of HF. Through this, Mamic believes this connection can be targeted for both therapy and diagnosis of HF.

However, Mamic cautions that the prospect of using the gut microbiome as a preventative – and potentially therapeutic – target in heart failure is a way off. Many larger and comprehensive clinical studies are needed before any aspect of this correlation can be adapted to clinical practice.

“I think it may become one of the important biomarkers that we use to take care of our patients, but I will say that we are very far from that, and we need a lot more data and much better understanding of how to interpret some of the microbiome features that we see in our patients,” Mamic said in the interview.

Mamic P, Chaikijurajai T, Tang WHW. Gut microbiome - A potential mediator of pathogenesis in heart failure and its comorbidities: State-of-the-art review. J Mol Cell Cardiol. 2021;152:105-117. 

Mamic P, Snyder M, Tang WHW. Gut microbiome-based management of patients with heart failure. Journal of the American College of Cardiology. 2023;81(17):1729-1739. 

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If this connection is proven, the gut microbiome may present an entirely new pathway for treatment and prevention of heart failure.

Petra Mamic, MD

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