Isolation and Quantification of Uremic Toxin Precursor-Generating Gut Bacteria in Chronic Kidney Disease Patients

International Journal of Molecular Sciences

Mario Vaneechoutte¹  Tessa Gryp²  Griet Glorieux²  Wim Van Biesen²  GeertR.B. Huys³  Marie Joossens³ 

[1] Department of Diagnostic Sciences, Laboratory Bacteriology Research, Ghent University, 9000 Ghent, Belgium;Department of Internal Medicine and Pediatrics, Nephrology Section, Ghent University Hospital, 9000 Ghent, Belgium;Department of Microbiology, Immunology and Transplantation, Molecular Microbiology—Microbiome Research Lab, KU Leuven, 3000 Leuven, Belgium;

关键词: qpcr;    bacterial culture;    fecal bacteria;    chronic kidney disease;    protein-bound uremic toxins;    bacterial metabolization;    aromatic amino acids;    p-cresol;    indole;    indole-3-acetic acid;    phenol;   

DOI  :  10.3390/ijms21061986

来源: DOAJ

【 摘 要 】

In chronic kidney disease (CKD), impaired kidney function results in accumulation of uremic toxins, which exert deleterious biological effects and contribute to inflammation and cardiovascular morbidity and mortality. Protein-bound uremic toxins (PBUTs), such as p-cresyl sulfate, indoxyl sulfate and indole-3-acetic acid, originate from phenolic and indolic compounds, which are end products of gut bacterial metabolization of aromatic amino acids (AAA). This study investigates gut microbial composition at different CKD stages by isolating, identifying and quantifying PBUT precursor-generating bacteria. Fecal DNA extracts from 14 controls and 138 CKD patients were used to quantify total bacterial number and 11 bacterial taxa with qPCR. Moreover, isolated bacteria from CKD 1 and CKD 5 fecal samples were cultured in broth medium supplemented with AAA under aerobic and anaerobic conditions, and classified as PBUT precursor-generators based on their generation capacity of phenolic and indolic compounds, measured with U(H)PLC. In total, 148 different fecal bacterial species were isolated, of which 92 were PBUT precursor-generators. These bacterial species can be a potential target for reducing PBUT plasma levels in CKD. qPCR indicated lower abundance of short chain fatty acid-generating bacteria, Bifidobacterium spp. and Streptococcus spp., and higher Enterobacteriaceae and E. coli with impaired kidney function, confirming an altered gut microbial composition in CKD.

【 授权许可】

Unknown