Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease
| العنوان: | Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease |
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| المؤلفون: | Takehiro Suzuki, Yotaro Matsumoto, Chikahisa Mukawa, Tomoya Tsukimi, Jun Wada, Hiroki Tsukamoto, Yuji Oe, Takaaki Abe, Naoto Suzuki, Nobuyuki Takahashi, Tetsuro Matsuhashi, Yuji Owada, Jurgen Heymann, Hiroaki Yamaguchi, Yukako Akiyama, Chitose Suzuki, Paxton Thanai, Ritsumi Saito, Satoshi Shimada, Ching Chin Yang, Tomohiro Nakamura, Fumika Nanto-Hara, Susumu Ogawa, Daisuke Saigusa, Matthew C. Breeggemann, Koichi Kikuchi, Masayuki Yamamoto, Akihiro Matsuo, Yoshitomi Kanemitsu, Jeffrey B. Kopp, Shinji Fukuda, Sadayoshi Ito, Tomoyuki Iwasaki, Yasutoshi Akiyama, Mariko Ichijo, Atsushi Hozawa, Miho Shimizu, Toshihiro Sato, Takafumi Toyohara, Yoshihisa Tomioka, Tomoyoshi Soga, Yoshiaki Ogata, Nariyasu Mano, Koki Mise, Jiro Ogura, Eikan Mishima, Noriko N. Fukuda, Takashi Suzuki, Shizuko Nagao, Kei Asaji, Takashi Wada, Yusuke Ohsaki, Hisato Shima, Hsin Jung Ho, Yoshitsugu Oikawa, Shigeo Kure |
| المصدر: | Nature Communications Nature Communications, Vol 10, Iss 1, Pp 1-17 (2019) |
| بيانات النشر: | Nature Publishing Group UK, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, General Physics and Astronomy, Organic Anion Transporters, 02 engineering and technology, Diabetic nephropathy, urologic and male genital diseases, Podocyte, Madin Darby Canine Kidney Cells, Animals, Genetically Modified, Cohort Studies, Mice, Diabetic Nephropathies, Enzyme Inhibitors, lcsh:Science, Tyrosine Phenol-Lyase, Aged, 80 and over, Kidney, Multidisciplinary, Proteinuria, Podocytes, Sulfates, Middle Aged, 021001 nanoscience & nanotechnology, medicine.anatomical_structure, Female, medicine.symptom, 0210 nano-technology, Adult, medicine.medical_specialty, Science, Sulfuric Acid Esters, General Biochemistry, Genetics and Molecular Biology, Streptozocin, Article, Diabetes Mellitus, Experimental, 03 medical and health sciences, Young Adult, Dogs, Diabetes mellitus, Internal medicine, medicine, Diabetes Mellitus, Animals, Metabolomics, Albuminuria, Humans, Aged, business.industry, urogenital system, General Chemistry, medicine.disease, Rats, Gastrointestinal Microbiome, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, Diabetes Mellitus, Type 1, Early Diagnosis, Diabetes Mellitus, Type 2, lcsh:Q, Microalbuminuria, Microbiome, business, Kidney disease |
| الوصف: | 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. Diabetes is a major cause of kidney disease. Here Kikuchi et al. show that phenol sulfate, a gut microbiota-derived metabolite, is increased in diabetic kidney disease and contributes to the pathology by promoting kidney injury, suggesting phenyl sulfate could be used a marker and therapeutic target for the treatment of diabetic kidney disease. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f53539ee350baef3ab3064425f4e6578Test http://europepmc.org/articles/PMC6478834Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f53539ee350baef3ab3064425f4e6578 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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