Neal B Shah1, Andrew S Allegretti2, Sagar U Nigwekar2, Sahir Kalim2, Sophia Zhao2, Benjamin Lelouvier3, Florence Servant3, Gloria Serena4, Ravi Ishwar Thadhani2,5, Dominic S Raj6, Alessio Fasano4. 1. Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; nbshah@bwh.harvard.edu. 2. Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. 3. Vaiomer, Department of Research and Development, Bioinformatics Division, Labège, France. 4. Division of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Massachusetts General Hospital for Children, Boston, Massachusetts. 5. Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California; and. 6. Division of Renal Diseases and Hypertension, The George Washington University, Washington, DC.
Abstract
BACKGROUND AND OBJECTIVES: The association between gut dysbiosis, high intestinal permeability, and endotoxemia-mediated inflammation is well established in CKD. However, changes in the circulating microbiome in patients with CKD have not been studied. In this pilot study, we compare the blood microbiome profile between patients with CKD and healthy controls using 16S ribosomal DNA sequencing. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Blood bacterial DNA was studied in buffy coat samples quantitatively by 16S PCR and qualitatively by 16S targeted metagenomic sequencing using a molecular pipeline specifically optimized for blood samples in a cross-sectional study comparing 20 nondiabetic patients with CKD and 20 healthy controls. RESULTS: There were 22 operational taxonomic units significantly different between the two groups. 16S metagenomic sequencing revealed a significant reduction in α diversity (Chao1 index) in the CKD group compared with healthy controls (127±18 versus 145±31; P=0.04). Proteobacteria phylum, Gammaproteobacteria class, and Enterobacteriaceae and Pseudomonadaceae families were more abundant in the CKD group compared with healthy controls. Median 16S ribosomal DNA levels did not significantly differ between CKD and healthy groups (117 versus 122 copies/ng DNA; P=0.38). GFR correlated inversely with the proportion of Proteobacteria (r=-0.54; P≤0.01). CONCLUSIONS: Our pilot study demonstrates qualitative differences in the circulating microbiome profile with lower α diversity and significant taxonomic variations in the blood microbiome in patients with CKD compared with healthy controls.
BACKGROUND AND OBJECTIVES: The association between gut dysbiosis, high intestinal permeability, and endotoxemia-mediated inflammation is well established in CKD. However, changes in the circulating microbiome in patients with CKD have not been studied. In this pilot study, we compare the blood microbiome profile between patients with CKD and healthy controls using 16S ribosomal DNA sequencing. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Blood bacterial DNA was studied in buffy coat samples quantitatively by 16S PCR and qualitatively by 16S targeted metagenomic sequencing using a molecular pipeline specifically optimized for blood samples in a cross-sectional study comparing 20 nondiabeticpatients with CKD and 20 healthy controls. RESULTS: There were 22 operational taxonomic units significantly different between the two groups. 16S metagenomic sequencing revealed a significant reduction in α diversity (Chao1 index) in the CKD group compared with healthy controls (127±18 versus 145±31; P=0.04). Proteobacteria phylum, Gammaproteobacteria class, and Enterobacteriaceae and Pseudomonadaceae families were more abundant in the CKD group compared with healthy controls. Median 16S ribosomal DNA levels did not significantly differ between CKD and healthy groups (117 versus 122 copies/ng DNA; P=0.38). GFR correlated inversely with the proportion of Proteobacteria (r=-0.54; P≤0.01). CONCLUSIONS: Our pilot study demonstrates qualitative differences in the circulating microbiome profile with lower α diversity and significant taxonomic variations in the blood microbiome in patients with CKD compared with healthy controls.
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