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2017 Fiscal Year Final Research Report

Gut-renal axis: microbiota and chronic kidney disease

Research Project

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Project/Area Number 16K19474
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Kidney internal medicine
Research InstitutionTohoku University

Principal Investigator

Eikan Mishima  東北大学, 大学病院, 助教 (00706939)

Project Period (FY) 2016-04-01 – 2018-03-31
Keywords腸腎連関 / 慢性腎臓病 / 腸内細菌叢 / メタボローム / メタゲノム / 尿毒素 / 短鎖脂肪酸 / 無菌マウス
Outline of Final Research Achievements

Microbiota is involved in pathophysiology of renal disease such as accumulation of uremic solutes. We compared renal failure and control mice under germ-free or specific pathogen-free (SPF) conditions, examining the metabolite profiles using CE-TOFMS. We revealed that 11 solutes were considered microbiota-derived uremic solutes. Additionally, germ-free renal failure conditions resulted in the disappearance of colonic short-chain fatty acids, decreased utilization of intestinal amino acids, and more severe renal damage compared with SPF mice with renal failure. Thus, microbiota contributes to the production of harmful uremic solutes, but conversely, growth without microbiota has harmful effects on CKD progression. We examined the effect of canagliflozin, a SGLT inhibitor, on the accumulation of uremic toxins using renal failure mice. Canagliflozin treatment significantly reduced the plasma levels of p-cresyl sulfate and indoxyl sulfate and altered the microbiota composition.

Free Research Field

腎臓内科学

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Published: 2019-03-29  

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