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-Hara & 36 others Jiro 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

4 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

Fingerprint

kidney diseases
Albuminuria
Diabetic Nephropathies
Sulfates
sulfates
tyrosine
Medical problems
progressions
phenols
rats
Tyrosine Phenol-Lyase
Rats
transporter
Podocytes
Metabolomics
metabolites
kidneys
Disease Management
Metabolites
Phenol

ASJC Scopus subject areas

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

Cite this

Kikuchi, K., Saigusa, D., Kanemitsu, Y., Matsumoto, Y., Thanai, P., Suzuki, N., ... 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

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

In: Nature communications, Vol. 10, No. 1, 1835, 01.12.2019.

Research output: Contribution to journalArticle

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, NN, Ho, HJ, Nanto-Hara, F, Ogura, J, Saito, R, Nagao, S, Ohsaki, Y, Shimada, S, Suzuki, T, Toyohara, T, Mishima, E, Shima, H, Akiyama, Y, Akiyama, Y, Ichijo, M, Matsuhashi, T, Matsuo, A, Ogata, Y, Yang, CC, Suzuki, C, Breeggemann, MC, Heymann, J, Shimizu, M, Ogawa, S, Takahashi, N, Suzuki, T, Owada, Y, Kure, S, Mano, N, Soga, T, Wada, T, Kopp, JB, Fukuda, S, Hozawa, A, Yamamoto, M, Ito, S, Wada, J, Tomioka, Y & Abe, T 2019, 'Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease', Nature communications, vol. 10, no. 1, 1835. https://doi.org/10.1038/s41467-019-09735-4
Kikuchi, Koichi ; Saigusa, Daisuke ; Kanemitsu, Yoshitomi ; Matsumoto, Yotaro ; Thanai, Paxton ; Suzuki, Naoto ; Mise, Koki ; Yamaguchi, Hiroaki ; Nakamura, Tomohiro ; Asaji, Kei ; Mukawa, Chikahisa ; Tsukamoto, Hiroki ; Sato, Toshihiro ; Oikawa, Yoshitsugu ; Iwasaki, Tomoyuki ; Oe, Yuji ; Tsukimi, Tomoya ; Fukuda, Noriko N. ; Ho, Hsin Jung ; Nanto-Hara, Fumika ; Ogura, Jiro ; Saito, Ritsumi ; Nagao, Shizuko ; Ohsaki, Yusuke ; Shimada, Satoshi ; Suzuki, Takehiro ; Toyohara, Takafumi ; Mishima, Eikan ; Shima, Hisato ; Akiyama, Yasutoshi ; Akiyama, Yukako ; Ichijo, Mariko ; Matsuhashi, Tetsuro ; Matsuo, Akihiro ; Ogata, Yoshiaki ; Yang, Ching Chin ; Suzuki, Chitose ; Breeggemann, Matthew C. ; Heymann, Jurgen ; Shimizu, Miho ; Ogawa, Susumu ; Takahashi, Nobuyuki ; Suzuki, Takashi ; Owada, Yuji ; Kure, Shigeo ; Mano, Nariyasu ; Soga, Tomoyoshi ; Wada, Takashi ; Kopp, Jeffrey B. ; Fukuda, Shinji ; Hozawa, Atsushi ; Yamamoto, Masayuki ; Ito, Sadayoshi ; Wada, Jun ; Tomioka, Yoshihisa ; Abe, Takaaki. / Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease. In: Nature communications. 2019 ; Vol. 10, No. 1.
@article{9ae7a1c0e7c04b479629f796facf396a,
title = "Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease",
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.",
author = "Koichi Kikuchi and Daisuke Saigusa and Yoshitomi Kanemitsu and Yotaro Matsumoto and Paxton Thanai and Naoto Suzuki and Koki Mise and Hiroaki Yamaguchi and Tomohiro Nakamura and Kei Asaji and Chikahisa Mukawa and Hiroki Tsukamoto and Toshihiro Sato and Yoshitsugu Oikawa and Tomoyuki Iwasaki and Yuji Oe and Tomoya Tsukimi and Fukuda, {Noriko N.} and Ho, {Hsin Jung} and Fumika Nanto-Hara and Jiro Ogura and Ritsumi Saito and Shizuko Nagao and Yusuke Ohsaki and Satoshi Shimada and Takehiro Suzuki and Takafumi Toyohara and Eikan Mishima and Hisato Shima and Yasutoshi Akiyama and Yukako Akiyama and Mariko Ichijo and Tetsuro Matsuhashi and Akihiro Matsuo and Yoshiaki Ogata and Yang, {Ching Chin} and Chitose Suzuki and Breeggemann, {Matthew C.} and Jurgen Heymann and Miho Shimizu and Susumu Ogawa and Nobuyuki Takahashi and Takashi Suzuki and Yuji Owada and Shigeo Kure and Nariyasu Mano and Tomoyoshi Soga and Takashi Wada and Kopp, {Jeffrey B.} and Shinji Fukuda and Atsushi Hozawa and Masayuki Yamamoto and Sadayoshi Ito and Jun Wada and Yoshihisa Tomioka and Takaaki Abe",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41467-019-09735-4",
language = "English",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease

AU - Kikuchi, Koichi

AU - Saigusa, Daisuke

AU - Kanemitsu, Yoshitomi

AU - Matsumoto, Yotaro

AU - Thanai, Paxton

AU - Suzuki, Naoto

AU - Mise, Koki

AU - Yamaguchi, Hiroaki

AU - Nakamura, Tomohiro

AU - Asaji, Kei

AU - Mukawa, Chikahisa

AU - Tsukamoto, Hiroki

AU - Sato, Toshihiro

AU - Oikawa, Yoshitsugu

AU - Iwasaki, Tomoyuki

AU - Oe, Yuji

AU - Tsukimi, Tomoya

AU - Fukuda, Noriko N.

AU - Ho, Hsin Jung

AU - Nanto-Hara, Fumika

AU - Ogura, Jiro

AU - Saito, Ritsumi

AU - Nagao, Shizuko

AU - Ohsaki, Yusuke

AU - Shimada, Satoshi

AU - Suzuki, Takehiro

AU - Toyohara, Takafumi

AU - Mishima, Eikan

AU - Shima, Hisato

AU - Akiyama, Yasutoshi

AU - Akiyama, Yukako

AU - Ichijo, Mariko

AU - Matsuhashi, Tetsuro

AU - Matsuo, Akihiro

AU - Ogata, Yoshiaki

AU - Yang, Ching Chin

AU - Suzuki, Chitose

AU - Breeggemann, Matthew C.

AU - Heymann, Jurgen

AU - Shimizu, Miho

AU - Ogawa, Susumu

AU - Takahashi, Nobuyuki

AU - Suzuki, Takashi

AU - Owada, Yuji

AU - Kure, Shigeo

AU - Mano, Nariyasu

AU - Soga, Tomoyoshi

AU - Wada, Takashi

AU - Kopp, Jeffrey B.

AU - Fukuda, Shinji

AU - Hozawa, Atsushi

AU - Yamamoto, Masayuki

AU - Ito, Sadayoshi

AU - Wada, Jun

AU - Tomioka, Yoshihisa

AU - Abe, Takaaki

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85064911992&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064911992&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-09735-4

DO - 10.1038/s41467-019-09735-4

M3 - Article

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 1835

ER -