BACKGROUND: Gut microbial imbalance may contribute to endotoxemia, inflammation, and oxidative stress in heart failure (HF). Changes occurring in the intestinal microbiota and inflammatory/oxidative milieu during HF progression and following left ventricular assist device (LVAD) or heart transplantation (HT) are unknown. We aimed to investigate variation in gut microbiota and circulating biomarkers of endotoxemia, inflammation, and oxidative stress in patients with HF (New York Heart Association, Class I–IV), LVAD, and HT. METHODS: We enrolled 452 patients. Biomarkers of endotoxemia (lipopolysaccharide and soluble [sCD14]), inflammation (C-reactive protein, interleukin-6, tumor necrosis factor-α, and endothelin-1 adiponectin), and oxidative stress (isoprostane) were measured in 644 blood samples. A total of 304 stool samples were analyzed using 16S rRNA sequencing. RESULTS: Gut microbial community measures of alpha diversity were progressively lower across worsening HF class and were similarly reduced in patients with LVAD and HT (p < 0.05). Inflammation and oxidative stress were elevated in patients with Class IV HF vs all other groups (all p < 0.05). Lipopolysaccharide was elevated in patients with Class IV HF (vs Class I–III) as well as in patients with LVAD and HT (p < 0.05). sCD14 was elevated in patients with Class IV HF and LVAD (vs Class I–III, p < 0.05) but not in patients with HT. CONCLUSIONS: Reduced gut microbial diversity and increased endotoxemia, inflammation, and oxidative stress are present in patients with Class IV HF. Inflammation and oxidative stress are lower among patients with LVAD and HT relative to patients with Class IV HF, whereas reduced gut diversity and endotoxemia persist in LVAD and HT.
Bibliographical noteFunding Information:
This publication was supported by the Susan and Lowell McAdam educational grant, New York, NY, and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number UL1TR001873. P. C. C., Consultant, Abbott, no honoraria. Research Grant, Abbott. Y.N., Consultant, Abbott, Hourly base reimbursement. R.T.D. and P.C.C. also receive support from R01 DK102932. The sum of payment does not exceed $5,000/year. Consultant, CryoLife, Hourly base reimbursement. The sum of payment does not exceed $5,000/year. The remaining authors have no conflict of interest to declare.
© 2020 International Society for Heart and Lung Transplantation
- gut dysbiosis
- heart failure
- heart transplantation
- left ventricular assist device
- oxidative stress
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't
- Research Support, N.I.H., Extramural