Heart failure represents the terminal phase of diverse cardiovascular ailments, denoting the aberrant structure or functioning of the heart, leading to compromised ventricular filling or impaired ejection capacit.1 Consequently, the heart fails to efficiently pump blood, thereby falling short of meeting the body's metabolic demandsy.2 Clinically, this condition manifests as systemic or pulmonary circulation stagnation and inadequate perfusion in various bodily tissues and organs.Currently, the treatment approach for heart failure primarily revolves around diuretics,angiotensin-converting enzyme inhibitors,β receptor blockers,and other pharmacological interventions.3 However, owing to the intricate and variable etiology of heart failure,it often accompanies numerous complications, resulting in suboptimal treatment outcomes and patient prognosis. Globally, this ailment has emerged as a significant public health concern, imposing incalculable economic burdens on both society and families, while profoundly impacting the patients' quality of life and life expectancy. With the escalating global trend of population aging, the incidence of heart failure has witnessed a steep rise, underscoring the paramount importance of investigating its pathogenesis and devising effective treatment strategies.4

In recent times, the intricate connection between gut microbiota and its derivatives and cardiovascular well-being has garnered considerable attention.5 As the most extensive and intricate microbial assemblage within the human body, the gut microbiota comprises a myriad of bacteria, fungi, viruses, and other microorganisms.6 It assumes a pivotal role in immune regulation, nutrient absorption, metabolite synthesis, and other vital facets of human physiology, dynamically interacting with the host and significantly influencing human health and the onset and progression of diseases.7 An increasing body of research highlights the potential linkage between gut microbiota imbalance and the emergence and advancement of cardiovascular ailments, including heart failure. Initial observational studies have observed pronounced disparities in the gut microbiota composition between heart failure patients and healthy individuals.8, 9, 10 Certain species exhibit heightened abundance within the gut microbiota of heart failure patients, while others demonstrate a decline. This dysbiosis of the microbiota corresponds to the inflammatory state observed in heart failure patients and is intricately intertwined with cardiac dysfunction and adverse prognostic outcomes.11,12 Despite providing preliminary evidence of association, observational studies solely elucidate correlations and remain insufficient to definitively establish the causative relationship between gut microbiota and heart failure. Hence, a more comprehensive investigation is imperative to delve into the causal connection between gut microbiota and heart failure, ultimately furnishing precise guidelines for clinical practices and scientific research endeavors.

The application of Mendelian randomization analysis, a statistical model employing genetic variation as an instrumental variable, holds the capacity to assess the causal association between exposure factors and outcome variables.13 Through the utilization of inherent genetic variations bestowed upon individuals at birth, which are typically detached from confounding factors and biases, the influence of potential confounders and reverse causality is circumvented.14 Consequently, this methodology yields a potent approach, furnishing more dependable evidence when investigating the Consequently, this methodology yields a potent approach, furnishing more dependable evidence when investigating the causal link between specific factors and diseases or other outcomes. In line with these principles, the primary objective of this study is to explicate the conceivable causal relationship between gutmicrobiota and heart failure, employing the Mendelian randomization approach, thereby fostering progressive advancements within the domain of heart failure research.