MO137DIFFERENCES IN GUT MICROBIOTA PROFILES AND FUNCTIONS BETWEEN END-STAGE KIDNEY DISEASE AND HEALTHY POPULATIONS

Abstract

Abstract Background and Aims Patients with end-stage kidney disease (ESKD) are characterized by altered gut microbiota, impaired intestinal barrier function, and experienced gut microbiota-derived metabolites related to systemic complications. However, limited studies evaluated the microbial diversity and function in ESKD patients previously. Method Compared to age- and gender-matched subjects without kidney disease, 82 ESKD patients in the discovery cohort and 58 ESKD patients in the validation cohort were investigated for the microbial richness, biodiversity, gut dysbiosis, microbial composition differences, and the functional changes by gut metabolic module analysis. Bacterial derived free form protein-bound uremic toxins were analyzed by mass spectrometry and their association with microbial richness in ESKD patients was determined. Results Compared to controls, an increased α-diversity and distinct β-diversity were found in ESKD (Figure). The increase in α-diversity was correlated with protein-bound uremic toxins, particularly hippuric acid. A higher microbial dysbiosis index (MDI) was found in ESKD patients with the following enriched genera: Facealibacterium, Ruminococcus, Fusobacterium, Dorea, Anaerovorax, Sarcina, Akkermansia, Streptococcus, and Dysgonomonas. MDI at the genus level successfully differentiated between ESKD and controls in the discovery cohort (area under the curve [AUC] of 81.9%) and the validation cohort (AUC of 83.2%). Regarding functional enrichment analysis with gut metabolic modules, ESKD subjects presented with gut microbial function of increased saccharide and amino acid metabolism compared with matched controls. Conclusion An enriched but dysbiotic gut microbiota was presented in ESKD patients, in which the bacteria that were present increase amino acid metabolism linked to the production of protein-bound uremic toxins.