Title : Targeting the gut-heart axis: Exploring the role of the gut microbiome in cancer therapy-induced cardiotoxicity and prospects for microbiome-based prevention
Abstract:
Cardiotoxicity makes it harder to maximize cancer survival rates; radiation and chemotherapy do more than just harm cells directly; they also worsen irreversible heart damage. By addressing a significant knowledge vacuum about the precise role of the gut microbiome in cardiotoxicity, this study intends to examine the gut microbiota as a possible moderator of this phenomena in relation to cancer treatments. This study presents a new perspective on the gut-heart axis based on the idea that chemotherapy-induced dysbiosis increases cardiotoxicity by changing microbial metabolites like SCFAs and trimethylamine N-oxide (TMAO), which impact systemic inflammation, oxidative stress, and endothelial function. This study will develop drugs that target the microbiome by using a three-pronged translational strategy to decipher these relationships. Using state-of-the-art cardiac imaging (3D echocardiography, global longitudinal strain), plasma metabolomics (TMAO, butyrate), and serial metagenomic sequencing, we will prospectively enroll 200 breast cancer patients who are taking anthracyclines or immune checkpoint inhibitors (ICIs) and look for microbial signatures and metabolite profiles that indicate subclinical cardiac dysfunction. Secondly, we will be employing germ-free animals who are going through cancer treatments that are comparable to guinea pigs in order to find out if dysbiosis is associated with heart damage. We will be on the lookout for signs of decreased butyrate production by Bacteroidetes and increased tissue microbiota acidotrophic index (TMAO) by Proteobacteria. Using 60 high-risk patients (TMAO >6 µM, LVEF <55%), a proof-of-concept randomized trial will evaluate a customized probiotic formulation (Lactobacillus rhamnosus, Akkermansia muciniphila, and Bifidobacterium longum) with the goals of restoring microbial diversity, reducing TMAO (target: 40% reduction), and preserving cardiac function (primary endpoint: ΔLVEF ≥ 5%). Identifying which patient subsets are most responsive to changes in their microbiome requires integrating omics data with machine learning-driven clustering. This will allow for reliable risk stratification. By shifting the emphasis to the microbiota, this study challenges the status quo of reactive cardio-oncology therapy and offers a proactive strategy for reducing cardiotoxicity. The research aims to uncover the molecular involvement of the gut microbiota and evaluate a scalable, low-cost intervention with the goal of rethinking preventive cardiology in cancer therapy, especially in contexts with limited resources when advanced treatments are unavailable. The findings will pave the way for more extensive clinical investigations and recommendations by shedding light on microbial metabolites as potential novel biomarkers and therapies. In order to better balance the short- and long-term impacts of oncologic therapy on cardiovascular health, this study bridges a vital gap by merging cardio-oncology with cutting-edge microbiome research.
