Abstract 15952: Gut Microbiota and Insulin Resistance in Heart Failure

Introduction/Hypothesis: Insulin resistance (IR) and heart failure (HF) are closely interconnected - IR is a risk factor for HF and can develop as a consequence of chronic HF. Dysregulation of the gut microbiota (GMB) has been independently associated with both HF and IR, with many overlapping GMB features. We hypothesized that the HF-associated GMB changes may be confounded by concomitant IR. Methods: Our study recruited 60 non-diabetic adults with non-ischemic cardiomyopathy and HF. As controls we included 49 non-diabetic adults. We profiled GMB using whole genome sequencing. Degree of IR was assessed by fasting Homeostatic Model Assessment of IR (HOMA-IR). Results: Study participants were largely middle aged (median age 53.6 years), white (65%), and overweight (median body mass index (BMI) 28.5 kg/m2). Men were over-represented in the HF group, compared to controls (78% vs 48%). Mean left ventricular ejection fraction was 30.5% in the HF group, and most HF patients had mild symptoms. Both groups had elevated HOMA-IR (median 2.5). According to beta-diversity analysis based on Bray-Curtis distances, both taxonomic and functional GMB structure were significantly different in HF, compared to controls (ANOSIM p<0.001) (Figure 1). Similar analysis of IR-associated GMB structure did not show significant separation (Figure 2). Taxa and metabolic pathways contributing to HF-associated GMB differences (Table 2) remained significant after controlling for HOMA-IR, age, sex, race, and BMI. Conclusions: We confirmed independent association between HF and taxonomic and functional GMB community shifts, but did not demonstrate a direct relationship between comorbid IR (as measured by HOMA-IR) and the GMB changes in HF. More precise and accurate measurement of IR than HOMA-IR may be needed to allow better characterization of the GMB-IR relationship in HF, and hopefully enable identification of novel preventative, diagnostic, and therapeutic targets in this disease.