Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 525, Issue 3, Pages 773-779Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2020.02.141
Keywords
Chronic kidney disease; Indole; p-cresol; AST-120
Categories
Funding
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- Japan Society for the Promotion of Science [16K09599, 19K08669, 18H02674, 18K17997]
- Japan Agency for Medical Research and Development (AMED) [JP17fk0108223h0002, JP17ek0410032s0102, JP17fk0108207h0002, JP17ek0210078h0002, JP17ak0101068h0001, JP17gm1010006s0101, JP18ck0106243h0003, JP19ek0410062h0001]
- Ministry of Health, Labor, and Welfare of Japan [19KA3001]
- Grants-in-Aid for Scientific Research [18H02674, 18K17997, 19K08669, 16K09599] Funding Source: KAKEN
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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 AST120 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. (C) 2020 Elsevier Inc. All rights reserved.
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