Next Article in Journal / Special Issue
Association between Free Light Chain Levels, and Disease Progression and Mortality in Chronic Kidney Disease
Previous Article in Journal
Antibacterial and Antidiarrheal Activities of Plant Products against Enterotoxinogenic Escherichia coli
Previous Article in Special Issue
Effects of Decreased Vitamin D and Accumulated Uremic Toxin on Human CYP3A4 Activity in Patients with End-Stage Renal Disease
Article Menu

Export Article

Open AccessReview
Toxins 2013, 5(11), 2042-2057;

From the Gastrointestinal Tract (GIT) to the Kidneys: Live Bacterial Cultures (Probiotics) Mediating Reductions of Uremic Toxin Levels via Free Radical Signaling

The University of Queensland, School of Medicine, Brisbane, St Lucia QLD 4072, Australia
Medlab, Sydney, New South Wales, Australia
Monash University, Melbourne VIC 3800, Australia
Centre for Kidney Disease Research, School of Medicine, Translational Research Institute at Princess Alexandra Hospital, The University of Queensland, Brisbane, St Lucia QLD 4072, Australia
Department of Nephrology, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane QLD 4102, Australia
Author to whom correspondence should be addressed.
Received: 2 September 2013 / Revised: 4 November 2013 / Accepted: 4 November 2013 / Published: 7 November 2013
(This article belongs to the Special Issue Uremic Toxins)
Full-Text   |   PDF [253 KB, uploaded 7 November 2013]


A host of compounds are retained in the body of uremic patients, as a consequence of progressive renal failure. Hundreds of compounds have been reported to be retention solutes and many have been proven to have adverse biological activity, and recognized as uremic toxins. The major mechanistic overview considered to contribute to uremic toxin overload implicates glucotoxicity, lipotoxicity, hexosamine, increased polyol pathway activity and the accumulation of advanced glycation end-products (AGEs). Until recently, the gastrointestinal tract (GIT) and its associated micro-biometabolome was a neglected factor in chronic disease development. A systematic underestimation has been to undervalue the contribution of GIT dysbiosis (a gut barrier-associated abnormality) whereby low-level pro-inflammatory processes contribute to chronic kidney disease (CKD) development. Gut dysbiosis provides a plausible clue to the origin of systemic uremic toxin loads encountered in clinical practice and may explain the increasing occurrence of CKD. In this review, we further expand a hypothesis that posits that environmentally triggered and maintained microbiome perturbations drive GIT dysbiosis with resultant uremia. These subtle adaptation responses by the GIT microbiome can be significantly influenced by probiotics with specific metabolic properties, thereby reducing uremic toxins in the gut. The benefit translates to a useful clinical treatment approach for patients diagnosed with CKD. Furthermore, the role of reactive oxygen species (ROS) in different anatomical locales is highlighted as a positive process. Production of ROS in the GIT by the epithelial lining and the commensal microbe cohort is a regulated process, leading to the formation of hydrogen peroxide which acts as an essential second messenger required for normal cellular homeostasis and physiological function. Whilst this critical review has focused on end-stage CKD (type 5), our aim was to build a plausible hypothesis for the administration of probiotics with or without prebiotics for the early treatment of kidney disease. We postulate that targeting healthy ROS production in the gut with probiotics may be more beneficial than any systemic antioxidant therapy (that is proposed to nullify ROS) for the prevention of kidney disease progression. The study and understanding of health-promoting probiotic bacteria is in its infancy; it is complex and intellectually and experimentally challenging. View Full-Text
Keywords: toxins; commensal bacteria; uremia; chronic kidney disease; probiotics; reactive oxygen species (ROS) toxins; commensal bacteria; uremia; chronic kidney disease; probiotics; reactive oxygen species (ROS)
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Share & Cite This Article

MDPI and ACS Style

Vitetta, L.; Linnane, A.W.; Gobe, G.C. From the Gastrointestinal Tract (GIT) to the Kidneys: Live Bacterial Cultures (Probiotics) Mediating Reductions of Uremic Toxin Levels via Free Radical Signaling. Toxins 2013, 5, 2042-2057.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top