Gut Microbiota and Their Derived Metabolites, a Search for Potential Targets to Limit Accumulation of Protein-Bound Uremic Toxins in Chronic Kidney Disease.

Abstract

Chronic kidney disease (CKD) is characterized by gut dysbiosis with a decrease in short-chain fatty acid (SCFA)-producing bacteria. Levels of protein-bound uremic toxins (PBUTs) and post-translational modifications (PTMs) of albumin increase with CKD, both risk factors for cardiovascular morbidity and mortality. The relationship between fecal metabolites and plasma concentrations of PBUTs in different stages of CKD (n = 103) was explored. Estimated GFR tends to correlate with fecal butyric acid (BA) concentrations (rs = 0.212; p = 0.032), which, in its turn, correlates with the abundance of SCFA-producing bacteria. Specific SCFAs correlate with concentrations of PBUT precursors in feces. Fecal levels of p-cresol correlate with its derived plasma UTs (p-cresyl sulfate: rs = 0.342, p < 0.001; p-cresyl glucuronide: rs = 0.268, p = 0.006), whereas an association was found between fecal and plasma levels of indole acetic acid (rs = 0.306; p = 0.002). Finally, the albumin symmetry factor correlates positively with eGFR (rs = 0.274; p = 0.005). The decreased abundance of SCFA-producing gut bacteria in parallel with the fecal concentration of BA and indole could compromise the intestinal barrier function in CKD. It is currently not known if this contributes to increased plasma levels of PBUTs, potentially playing a role in the PTMs of albumin. Further evaluation of SCFA-producing bacteria and SCFAs as potential targets to restore both gut dysbiosis and uremia is needed.

• Authors: Mieke Steenbeke, Sophie Valkenburg, Tessa Gryp, Wim Van Biesen, Joris R Delanghe, Marijn M Speeckaert, Griet Glorieux
• Journal: Toxins (Toxins (Basel)) Vol. 13 Issue 11 (11 17 2021) ISSN: 2072-6651 [Electronic] Switzerland
• PMID: 34822593 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Indoleacetic Acids
• Uremic Toxins
• Butyric Acid
• indoleacetic acid

Topics

• Butyric Acid (metabolism)
• Cohort Studies
• Dysbiosis (etiology)
• Feces (microbiology)
• Gastrointestinal Microbiome
• Humans
• Indoleacetic Acids (metabolism)
• Renal Insufficiency, Chronic (microbiology, physiopathology)
• Uremic Toxins (metabolism)