Differences in Gut Microbiota Profiles and Functions Between End-stage Renal Disease and Healthy Populations 

Abstract

Background: Patients with end-stage renal disease (ESRD) have extremely high risks of mortality and morbidity, as well as altered gut microbiota and impaired intestinal barrier function. The translocation of gut-derived molecules in ESRD contributes to systemic complications. In this study, we evaluated the gut microbiome difference in ESRD patients compared to age- and gender-matched subjects without kidney disease in discovery and validation cohorts.Results: Compared to controls with normal renal function, an increased α-diversity and distinct β-diversity were found in ESRD subjects. The increase in α-diversity was correlated with protein-bound uremic toxins, particularly hippuric acid. A higher microbial dysbiosis index (MDI) was found in ESRD patients with the following enriched genera: Facealibacterium, Ruminococcus, Fusobacterium, Dorea, Anaerovorax, Sarcina, Akkemansia, Streptococcus, and Dysgonomonas. MDI at the genus level demonstrated highly differentiated accuracies between ESRD and control subjects in the discovery cohort (area under the curve [AUC] of 81.9%) and between ESRD and control subjects in the validation cohort (AUC of 83.2%). On functional enrichment analysis with gut metabolic modules, ESRD subjects presented with increased saccharide and amino acid metabolism when compared with matched controls.Conclusions: An enriched but dysbiotic gut microbiota was presented in ESRD patients, in which the bacteria that were present increase amino acid metabolism linked to the production of protein-bound uremic toxins.

Ketoanalogs’ Effects on Intestinal Microbiota Modulation and Uremic Toxins Serum Levels in Chronic Kidney Disease (Medika2 Study)

“…Moreover, they are able to produce short chain fatty acids (SCFAs), i.e., acetic, propionic, and butyric acids [ 48 ]. Acetate and butyrate are essential in CKD patients, in which the accumulation of urea and ammonia drives the pH out of normal range [ 49 ], whereas SCFAs could bring back pH ranges into normal ones [ 50 ]. Additionally, lactobacilli and derived SCFAs contributes also to enhance the epithelial layer integrity [ 51 , 52 , 53 ], therefore reducing the translocation of microbes and metabolites (including urea, ammonia, and uremic toxins) into the systemic circulation, an evidence common in CKD patients [ 54 , 55 ].…”

In Vitro Selection of Probiotics, Prebiotics, and Antioxidants to Develop an Innovative Synbiotic (NatuREN G) and Testing Its Effect in Reducing Uremic Toxins in Fecal Batches from CKD Patients

“…In CKD, the dysbiotic, highly proteolytic, microbial patterns determine the increase in uremic toxins, e.g., IS and pCS, produced from urea and other nitrogenous compounds [ 8 ]. Moreover, due to low kidney functionality, CKD patients are unable to excrete waste metabolites (including urea, ammonia, and uremic toxins), which, in turn, contribute to pH increase in the intestinal environment [ 7 ]. Additionally, urea and ammonia are primarily involved in the tight junctions’ disruption in CKD [ 46 ].…”

“…In CKD, renal damage determines an accumulation of urea and nitrogenous compounds in both blood and intestinal lumen [ 6 ]. Therefore, urea and its derivatives (i.e., ammonia and other nitrogenous compounds) cause significant deviations in the optimal pH range of the gut, and both urea and intestinal pH strongly favor the proliferation of proteolytic bacteria [ 7 , 8 ]. From this point of view, the genomic potential of specific bacterial patterns (e.g., Proteobacteria and relative sub-taxa, such as Enterobacteriaceae ) determines the production of secondary metabolites, starting from the overabundant nitrogen compounds found in the intestinal lumen of nephropathic subjects [ 8 ].…”