
Evaluating the Prognostic Significance of the Blood Firmicutes-to-Bacteroidetes Ratio in Patients with Heart Failure with Reduced Ejection Fraction
Seyed Mohsen Mirhosseini 1 ©, Hossein Yarmohammadi 1, Mahdi Rezaei 1, Sina Esmaeili 2 ℗, Sina Shahshenas 2, Seyed Davar Siadat 3
Abstract
Background: Recent studies indicate that the blood microbiota might contribute to the development and advancement of cardiovascular diseases. While the Firmicutes-to-Bacteroidetes (F/B) ratio, an indicator of microbial balance, has been extensively examined in the gut, its relevance in the bloodstream and its predictive value for heart failure with reduced ejection fraction (HFrEF) are still not well understood. Methods: This prospective observational study involved 30 patients diagnosed with HFrEF (left ventricular ejection fraction below 40%) and 30 healthy controls matched for age and sex. At the start of the study, blood samples were collected from all participants. These samples were analyzed using quantitative real-time PCR to quantify the presence of Firmicutes and Bacteroidetes. The patients were then followed for a period of 12 months, during which their survival status was recorded at the 6-month and 12-month marks. To evaluate the diagnostic and prognostic significance of these microbial markers, ROC curve analysis and Cox regression were performed. Results: In patients with HFrEF, the abundance of Firmicutes was significantly lower, while Bacteroidetes abundance was notably higher compared to healthy controls (p0.0001), leading to a decreased F/B ratio (p=0.0003). Bacteroidetes showed excellent diagnostic accuracy in distinguishing HFrEF patients from controls, with an AUC of 1.0. Firmicutes also demonstrated strong diagnostic potential (AUC: 0.945). The F/B ratio provided moderate diagnostic value with an AUC of 0.771. From a prognostic perspective, a higher F/B ratio was strongly linked to better survival at 6 months (AUC: 0.913, HR: 1.28×10⁻⁹, p=0.0243) and remained a significant predictor at 12 months (AUC: 0.710, HR: 0.00059, p=0.041). Additionally, Firmicutes abundance showed a negative correlation with ProBNP levels (r = −0.55, p=0.0018). No significant differences in blood microbiota composition were found among patient subgroups categorized by medication use, history of cardiovascular surgery, atrial fibrillation, or presence of abdominal ascites. Conclusion: This study shows that the blood F/B ratio is markedly changed in HFrEF patients and could potentially be used as a valuable non-invasive biomarker for diagnosis as well as prognosis.
Keywords: Blood microbiome; Heart failure; Microbiota; Firmicutes; Bacteroidetes