Faculty Collaboration Database

Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease. Nat Commun 2019 Apr 23;10(1):1835

Date

04/25/2019

Pubmed ID

31015435

Pubmed Central ID

PMC6478834

DOI

10.1038/s41467-019-09735-4

Scopus ID

2-s2.0-85064911992 (requires institutional sign-in at Scopus site)   230 Citations

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 List

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

Author

Satoshi Shimada MD, PhD Instructor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Albuminuria
Animals
Animals, Genetically Modified
Cohort Studies
Diabetes Mellitus, Experimental
Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2
Diabetic Nephropathies
Dogs
Enzyme Inhibitors
Female
Gastrointestinal Microbiome
Humans
Madin Darby Canine Kidney Cells
Male
Metabolomics
Mice
Mice, Inbred C57BL
Middle Aged
Organic Anion Transporters
Podocytes
Rats
Streptozocin
Sulfuric Acid Esters
Tyrosine Phenol-Lyase
Young Adult