Gut microbiome correlations with cardiotoxicity biomarkers (LV-GLS, LVEF, Troponin I, NTproBNP) in breast cancer patients prior to chemotherapy

Links between the gut microbiome and a range of cardiovascular diseases such as heart failure, atherosclerosis and hypertension have been well established. However, there is very limited research on the role of the gut microbiome in chemotherapy-induced cardiotoxicity. Here, we investigate associations between the gut microbiome and several biomarkers of cardiotoxicity (LV-GLS, LVEF, Troponin I and NTproBNP) in breast cancer patients prior to anti-cancer treatment, aiming to bridge this critical gap in knowledge.

This research investigates the potential of microbiome-targeted interventions as strategies for mitigating chemotherapy-induced cardiotoxicity in breast cancer patients.

The ongoing CARDIOCARE Prospective Clinical Study (NCT06334445) recruited 98 women >60 years of age diagnosed with breast cancer at three clinical cancer treatment centres. At diagnosis (prior to the start of any chemotherapy treatment), echocardiogram assessments for cardiac functioning (LVEF, LV-GLS) as well as blood tests for Troponin I, BNP and pro-NT BNP were performed and faecal samples were collected for 16s metagenomics. DNA was isolated and purified from these faecal samples and analysed using the hypervariable regions of the 16S rRNA gene on an Illumina DNA sequencing platform. Bacterial abundance was adjusted for patient BMI and a Spearman’s correlation was used to detect the direction and strength of relationships between biomarkers and gut bacteria, while permutation analysis was employed to validate statistical significance.

The family Bacteroidaceae was found to be significantly positively associated with both LV-GLS and Troponin I (r=0.39, p<0.00032; r=0.21, p<0.042, respectively) with very similar results at the genus level (r=0.40, p<0.00022; r=0.21, p<0.043). At the species level, significant associations (p<0.05) were also found between LV-GLS, LVEF, Troponin I and NTproBNP involving several individual Bacteroides species.

Our findings suggest that the relative abundance of certain Bacteroides species prior to treatment were correlated with cardiovascular parameters which are known to be linked to an increased risk of cardiotoxicity following chemotherapy. Bacteroides are a prevalent commensal gut bacteria that are known to reduce inflammation through regulation of T lymphocytes functioning within the gut mucosa (1) and have been associated with cardiovascular disease including hypertension (2), variations in cardiac structure and systolic and diastolic dysfunction (3). Bacteroides fragilis has already been evaluated as a probiotic to mitigate gastrointestinal toxicity to chemotherapy (4) which highlights the potential of this approach for addressing chemotherapy-induced cardiotoxicity.