Introduction: Circulating biomarkers of congestion and inflammation correlate with poor clinical outcomes in heart failure (HF). Splanchnic venous congestion may alter intestinal barrier function and gut microbiota composition leading to inflammation. Microbial diversity is a new biomarker of health and metabolic capacity and is reduced in HF.
Hypotheses: Reduced microbial diversity is associated with congestion and inflammation in HF pts.
Methods: We enrolled 67 HF pts (NYHA class I-IV). CD146, endothelin-1 (ET-1), interleukin-6 (IL6), interleukin-10 (IL10), tumor necrosis factor-alpha (TNF-α), adiponectin and CRP were assessed in venous blood. Bacterial DNA was extracted from stool and V3-V4 16S rRNA was sequenced. Alpha-diversity (the number of taxa within pts) and beta-diversity (similarity in bacteria between pts) were calculated via standard methods. Multivariable models assessed the associations between diversity metrics, or bacterial taxa, and the aforementioned biomarkers.
Results: Pts were 60±13 y old, 29% female. Increased alpha diversity was related to reduced IL6, TNFα (p for both<0.05) and CRP (p=0.06). Beta diversity was related to CRP, TNFα (p for both<0.05) and IL6 (p=0.08). Several individual taxa were related to both inflammatory and congestion biomarkers (Figure). Increased F. prausnitzii was associated with decreased CRP, IL6 and TNFα (all p<0.05); R. faecis with decreased CRP, IL6, TNFα, IL10 and ET1 (all p<0.05); Cardiobacterium genera with increased CRP, IL6 and TNFα (all p<0.05). Over 50 taxa were associated with CD146 (biomarker of systemic congestion), including taxa in the Desulfovibrio genera (p<0.01), which has known relevance for cardiovascular physiology.
Conclusions: Reduced microbial diversity and specific gut microbiota are related to biomarkers of inflammation and congestion in HF pts. Future studies can investigate whether interventions targeting the gut microbiome may reduce the inflammatory state of HF.