title: The gut-kidney axis.
abstract: The host-gut microbiota interaction has been the focus of increasing interest in recent years. It has been determined that this complex interaction is not only essential to many aspects of normal "mammalian" physiology but that it may also contribute to a multitude of ailments, from the obvious case of inflammatory bowel disease to (complex) diseases residing in organs outside the gut. An increasing body of evidence indicates that crosstalk between host and microbiota is pathophysiologically relevant in patients with chronic kidney disease (CKD). Interactions are bidirectional; on the one hand, uremia affects both the composition and metabolism of the gut microbiota and, on the other hand, important uremic toxins originate from microbial metabolism. In addition, gut dysbiosis may induce a disruption of the epithelial barrier, ultimately resulting in increased exposure of the host to endotoxins. Due to dietary restrictions and gastrointestinal dysfunctions, microbial metabolism shifts to a predominantly proteolytic fermentation pattern in CKD. Indoxyl sulfate and p-cresyl sulfate, both end-products of protein fermentation, and trimethylamine-N-oxide, an end-product of microbial choline and carnitine metabolism, are prototypes of uremic toxins originating from microbial metabolism. The vascular and renal toxicity of these co-metabolites has been demonstrated extensively in experimental and clinical studies. These co-metabolites are an appealing target for adjuvant therapy in CKD. Treatment options include dietary therapy, prebiotics, probiotics and host and bacterial enzyme inhibitors. Final proof of the concept should come from randomized controlled and adequately powered intervention studies.
authors.affiliation: Laboratory of Nephrology, Department of Immunology and Microbiology, KU Leuven, Leuven, Belgium. Pieter.Evenepoel@uzleuven.be.|Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium. Pieter.Evenepoel@uzleuven.be.|Dienst Nefrologie, University Hospitals Leuven-Gasthuisberg campus, Herestraat 49, 3000, Leuven, Belgium. Pieter.Evenepoel@uzleuven.be.
authors.forename: Pieter
authors.initials: P
authors.lastname: Evenepoel
authors.affiliation: Laboratory of Nephrology, Department of Immunology and Microbiology, KU Leuven, Leuven, Belgium.|Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Ruben
authors.initials: R
authors.lastname: Poesen
authors.affiliation: Laboratory of Nephrology, Department of Immunology and Microbiology, KU Leuven, Leuven, Belgium.|Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Björn
authors.initials: B
authors.lastname: Meijers
mesh_terms: D000818:Animals; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D051436:Renal Insufficiency, Chronic / Q000378:metabolism / Q000382:microbiology*; D014511:Uremia / Q000378:metabolism* / Q000382:microbiology
keywords: Chronic kidney disease; Host–gut microbiota interaction; Microbial metabolism; Microbiome; Uremic toxins