A leaky and imbalanced gut could play a significant role in heart failure (HF, heart failure), potentially fueling its onset or worsening the condition. This is the takeaway from a recent study in Heart Failure Reviews, where the microbiome surfaces as a potential therapeutic target to safeguard the heart, alongside conventional drugs.
The Paradigms of Heart Failure
Age, hypertension, obesity, smoking, and diabetes are among the risk factors that can trigger HF, a condition in which the heart is no longer able to pump blood effectively, leading to fatigue, breathing difficulties, and a range of other consequences, including increased mortality.
In this clinical landscape, recent scientific investigations increasingly point to an evolving role for the gut microbiota and, in particular, the concept of “leaky gut”, the loss of intestinal barrier integrity, establishing a new and important heart–gut axis. There is evidence that in HF patients reduced intestinal perfusion compromises the mucosal lining, creating breaches and weakening the intestinal barrier: events that would facilitate the passage of bacterial toxins and the ingress of harmful metabolites into the bloodstream.
Among these substances is lipopolysaccharide (LPS), a component present in the outer membrane of Gram-negative bacteria that, once circulating, activates the TLR4 receptor on cardiomyocytes, triggering an inflammatory cascade with increased production of cytokines such as TNF-α, IL-1, and IL-6, involved in damage to cardiac tissue.
Alongside LPS, another metabolite to watch is TMAO (trimethylamine N-oxide), produced by gut bacteria, predominantly by Firmicutes and Proteobacteria, during digestion of choline and carnitine, which are abundant in red meat, eggs, and fish. TMAO has been linked, for example, to the development of atherosclerosis, endothelial dysfunction, inflammation, and cardiac fibrosis. The role of TMAO remains controversial: some studies suggest that in certain conditions it could have protective effects at low doses, although the more robust data tend to indicate a risk to the heart.
Immune System Weakening
Dysbiosis of the gut, beyond its effects on metabolism, also impacts the immune system by reducing regulatory T cells (Tregs), which normally keep inflammation in check, and by increasing Th17 cells, drivers of inflammatory responses: an imbalance frequently linked to the onset of cardiac dysfunction.
In terms of the gut microbial population, beneficial bacteria such as Bifidobacteria and Bacteroides decline, those producers of short-chain fatty acids (SCFAs) including butyrate, which help strengthen the gut barrier and dampen systemic inflammation through receptors like GPR41/43/109A and epigenetic mechanisms.
The Therapeutic Approaches
Heart failure is now treatable, depending on the case, with a combination of pharmacological, surgical, and/or lifestyle interventions, for example in the dietary sphere by increasing fruit and vegetable intake while reducing animal products, aligned with the Mediterranean or DASH diet models. Such dietary patterns are associated with lowering substrates for TMAO production and promoting the growth of SCFA-producing beneficial bacteria.
As is well known, diet modulates the gut microbiota, a potential therapeutic target alongside antibiotics, such as rifaximin, while prebiotics may also confer benefit, including Saccharomyces boulardii, which has historically been used in the management of this condition. In phase 2 clinical studies, this latter approach has not yet demonstrated consistent improvements in cardiac function, though small pilot studies hint at possible benefits for ejection fraction in patients treated with certain probiotics.
Consequently, phase I research is exploring, in animal models and other tools, approaches such as fecal microbiota transplantation, with results currently mixed and still far from standardized clinical application, as well as testing other probiotic strains. Researchers are also examining natural phytochemicals like allicin (the active compound in garlic), selected for their potential to modulate TMAO production.
In Conclusion
In the future, cardiology for treating certain specific conditions could find the gut to be a valuable ally.
Source
Shoukry AEA, Rahhal A, Constantinou C. The role of the gut microbiota and metabolites in heart failure and possible implications for treatment. Heart Failure Reviews, 2025. Doi: https://doi.org/10.1007/s10741-025-10546-7
Abbonati a Karla Miller
