Melana Yuzefpolskaya1, Bruno Bohn2, Mojdeh Nasiri1, Amelia M Zuver1, Drew D Onat1, Eugene A Royzman1, Joseph Nwokocha1, Melissa Mabasa1, Alberto Pinsino1, Danielle Brunjes1, Antonia Gaudig1, Autumn Clemons1, Pauline Trinh3, Stephania Stump4, Marla J Giddins4, Veli K Topkara1, A Reshad Garan1, Koji Takeda5, Hiroo Takayama5, Yoshifumi Naka5, Maryjane A Farr1, Renu Nandakumar6, Anne-Catrin Uhlemann4, Paolo C Colombo1, Ryan T Demmer7. 1. Division of Cardiology, Department of Medicine, New York Presbyterian Hospital, Columbia University, New York City, New York. 2. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota. 3. Department of Environmental and Occupational Health Sciences, University of Washington, School of Public Health, Seattle, Washington. 4. Department of Medicine, Division of Infectious Diseases and Microbiome and Pathogen Genomics Core, New York Presbyterian Hospital, Columbia University, New York City, New York. 5. Division of Cardiothoracic Surgery, Department of Surgery, New York Presbyterian Hospital, Columbia University, New York City, New York. 6. Biomarkers Core Laboratory, Irving Institute for Clinical and Translational Research, New York Presbyterian Hospital, Columbia University, New York City, New York. 7. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota; Division of Epidemiology, Mailman School of Public Health, Columbia University, New York City, New York. Electronic address: demm0009@umn.edu.
Abstract
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.
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-1adiponectin), 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.
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