Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease

Koichi Kikuchi, Daisuke Saigusa, Yoshitomi Kanemitsu, Yotaro Matsumoto, Paxton Thanai, Naoto Suzuki, Koki Mise, Hiroaki Yamaguchi, Tomohiro Nakamura, Kei Asaji, Chikahisa Mukawa, Hiroki Tsukamoto, Toshihiro Sato, Yoshitsugu Oikawa, Tomoyuki Iwasaki, Yuji Oe, Tomoya Tsukimi, Noriko N. Fukuda, Hsin Jung Ho, Fumika Nanto-HaraJiro Ogura, Ritsumi Saito, Shizuko Nagao, Yusuke Ohsaki, Satoshi Shimada, Takehiro Suzuki, Takafumi Toyohara, Eikan Mishima, Hisato Shima, Yasutoshi Akiyama, Yukako Akiyama, Mariko Ichijo, Tetsuro Matsuhashi, Akihiro Matsuo, Yoshiaki Ogata, Ching Chin Yang, Chitose Suzuki, Matthew C. Breeggemann, Jurgen Heymann, Miho Shimizu, Susumu Ogawa, Nobuyuki Takahashi, Takashi Suzuki, Yuji Owada, Shigeo Kure, Nariyasu Mano, Tomoyoshi Soga, Takashi Wada, Jeffrey B. Kopp, Shinji Fukuda, Atsushi Hozawa, Masayuki Yamamoto, Sadayoshi Ito, Jun Wada, Yoshihisa Tomioka, Takaaki Abe

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Diabetic kidney disease is a major cause of renal failure that urgently necessitates a breakthrough in disease management. Here we show using untargeted metabolomics that levels of phenyl sulfate, a gut microbiota-derived metabolite, increase with the progression of diabetes in rats overexpressing human uremic toxin transporter SLCO4C1 in the kidney, and are decreased in rats with limited proteinuria. In experimental models of diabetes, phenyl sulfate administration induces albuminuria and podocyte damage. In a diabetic patient cohort, phenyl sulfate levels significantly correlate with basal and predicted 2-year progression of albuminuria in patients with microalbuminuria. Inhibition of tyrosine phenol-lyase, a bacterial enzyme responsible for the synthesis of phenol from dietary tyrosine before it is metabolized into phenyl sulfate in the liver, reduces albuminuria in diabetic mice. Together, our results suggest that phenyl sulfate contributes to albuminuria and could be used as a disease marker and future therapeutic target in diabetic kidney disease.

Original languageEnglish
Article number1835
JournalNature communications
Volume10
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease'. Together they form a unique fingerprint.

  • Cite this

    Kikuchi, K., Saigusa, D., Kanemitsu, Y., Matsumoto, Y., Thanai, P., Suzuki, N., Mise, K., Yamaguchi, H., Nakamura, T., Asaji, K., Mukawa, C., Tsukamoto, H., Sato, T., Oikawa, Y., Iwasaki, T., Oe, Y., Tsukimi, T., Fukuda, N. N., Ho, H. J., ... Abe, T. (2019). Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease. Nature communications, 10(1), [1835]. https://doi.org/10.1038/s41467-019-09735-4