The gut microbiota and cardiac cachexia
Introduction: Progression of heart failure to advanced heart failure (AHF) has a very poor prognosis. Cardiac cachexia (CC) is a clinical indicator of AHF, encompassing the unintentional weight loss (UWL) of fat/muscle with other symptoms and signs. The gut microbiota (GM) is an area of pathogenic interest that has not been investigated in AHF patients with CC; this study aimed to address this.  Methods: Patients with AHF, with or without CC/UWL, and stable chronic HF were recruited from Harefield Hospital (part of Guy's and St Thomas' NHS Foundation Trust) following national ethical approval. Healthy control subjects (HCs) were also enrolled. Patients underwent assessment for CC/UWL and were provided with a validated stool kit for onward GM analysis. Bacterial DNA was extracted, quantified and bacterial 16s RNA gene sequencing performed. Statistical analyses were conducted comparing baseline characteristics, GM composition (via Wilcoxon rank sum and DESeq2 analyses across the taxonomic levels), alpha and beta diversity between AHF patients with CC/UWL (CC/UWL-AHF) and rest of cohort (ROC). Secondary analyses sought to compare AHF with HF groups, and those with a HF diagnosis (PwHF) versus HCs.   Results: 67 patients returned faecal samples and 14 were noted to have CC/UWL-AHF. No significant differences were observed at each taxonomic level between CC/UWL-AHF and ROC. Alpha diversity was also indifferent. A borderline-significant weak trend towards community compositional differences between CC/UWL-AHF and ROC was observed following beta diversity testing (R2=0.016, p<0.071). Secondary analysis revealed Lactobacillales (order) and Streptococcaceae (family) were more prevalent in PwHF than HCs (both adjusted p<0.05), whereas Comamonadaceae (family) bacteria were more prevalent in HCs (adjusted p<0.05). Finally, differential abundance testing revealed Streptococcus salivarius was enriched at a species level in PwHF versus HCs (log2 fold change 4.72, adjusted p<0.038).   Conclusion: In conclusion, patients with CC/UWL and AHF may exhibit subtle GM compositional changes. We also found GM alterations in HF when compared to HCs, consistent with current literature findings. Our study implores the need to explore GM changes in a larger cohort, coupled with data on gut metabolites, to better understand its role in CC pathogenesis.