Germ-Free Conditions Modulate Host Purine Metabolism, Exacerbating Adenine-Induced Kidney Damage

Eikan Mishima, Mariko Ichijo, Takeshi Kawabe, Koichi Kikuchi, Yukako Akiyama, Takafumi Toyohara, Takehiro Suzuki, Chitose Suzuki, Atsuko Asao, Naoto Ishii, Shinji Fukuda, Takaaki Abe

研究成果: Article査読

1 被引用数 (Scopus)

抄録

Alterations in microbiota are known to affect kidney disease conditions. We have previously shown that germ-free conditions exacerbated adenine-induced kidney damage in mice; however, the mechanism by which this occurs has not been elucidated. To explore this mechanism, we examined the influence of germ-free conditions on purine metabolism and renal immune responses involved in the kidney damage. Germ-free mice showed higher expression levels of purine-metabolizing enzymes such as xanthine dehydrogenase, which converts adenine to a nephrotoxic byproduct 2,8-dihydroxyadenine (2,8-DHA). The germ-free mice also showed increased urinary excretion of allantoin, indicating enhanced purine metabolism. Metabolome analysis demonstrated marked differences in the purine metabolite levels in the feces of germ-free mice and mice with microbiota. Furthermore, unlike the germ-free condition, antibiotic treatment did not increase the expression of purine-metabolizing enzymes or exacerbate adenine-induced kidney damage. Considering renal immune responses, the germ-free mice displayed an absence of renal IL-17A expression. However, the adenine-induced kidney damage in wild-type mice was comparable to that in IL-17A-deficient mice, suggesting that IL-17A does not play a major role in the disease condition. Our results suggest that the enhanced host purine metabolism in the germ-free mice potentially promotes the conversion of the administered adenine into 2,8-DHA, resulting in exacerbated kidney damage. This further suggests a role of the microbiota in regulating host purine metabolism.

本文言語English
論文番号547
ジャーナルToxins
12
9
DOI
出版ステータスPublished - 2020 9

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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