Effects of the oral adsorbent AST-120 on fecal p-cresol and indole levels and on the gut microbiota composition.

Abstract

In chronic kidney disease, elevated levels of circulating uremic toxins are associated with a variety of symptoms and organ dysfunction. Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) are microbiota-derived metabolites and representative uremic toxins. We have previously shown that the oral adsorbent AST-120 profoundly reduced pCS compared to IS in adenine-induced renal failure in mice. However, the mechanisms of the different attenuation effects of AST-120 between IS and pCS are unclear. To clarify the difference of AST-120 on IS and pCS, we investigated the levels of fecal indole and p-cresol, the respective precursors of IS and pCS, and examined the influence on the gut microbiota. Although fecal indole was detected in all groups analyzed, fecal p-cresol was not detected in AST-120 treatment groups. In genus level, a total of 23 organisms were significantly changed by renal failure or AST-120 treatment. Especially, AST-120 reduced the abundance of Erysipelotrichaceae uncultured and Clostridium sensu stricto 1, which have a gene involved in p-cresol production. Our findings suggest that, in addition to the adsorption of the uremic toxin precursors, AST-120 affects the abundance of some gut microbiota in normal and renal failure conditions, thereby explaining the different attenuation effects on IS and pCS.

• Authors: Emiko Sato, Koji Hosomi, Akiyo Sekimoto, Eikan Mishima, Yuji Oe, Daisuke Saigusa, Sadayoshi Ito, Takaaki Abe, Hiroshi Sato, Jun Kunisawa, Toshimitsu Niwa, Nobuyuki Takahashi
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 525 Issue 3 Pg. 773-779 (05 07 2020) ISSN: 1090-2104 [Electronic] United States
• PMID: 32147096 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Cresols
• Indoles
• Oxides
• 4-cresol
• Carbon
• indole
• AST 120

Topics

• Administration, Oral
• Adsorption
• Animals
• Bacteria (drug effects)
• Carbon (administration & dosage, pharmacology)
• Cresols (metabolism)
• Feces (chemistry)
• Gastrointestinal Microbiome (drug effects)
• Indoles (metabolism)
• Kidney Failure, Chronic (microbiology, pathology)
• Male
• Mice, Inbred C57BL
• Oxides (administration & dosage, pharmacology)