Dataset Information

Gut microbiota-derived D-serine protects against acute kidney injury.

ABSTRACT: Gut microbiota-derived metabolites play important roles in health and disease. D-amino acids and their L-forms are metabolites of gut microbiota with distinct functions. In this study, we show the pathophysiologic role of D-amino acids in association with gut microbiota in humans and mice with acute kidney injury (AKI). In a mouse kidney ischemia/reperfusion model, the gut microbiota protected against tubular injury. AKI-induced gut dysbiosis contributed to the altered metabolism of D-amino acids. Among the D-amino acids, only D-serine was detectable in the kidney. In injured kidneys, the activity of D-amino acid oxidase was decreased. Conversely, the activity of serine racemase was increased. The oral administration of D-serine mitigated the kidney injury in B6 mice and D-serine-depleted mice. D-serine suppressed hypoxia-induced tubular damage and promoted posthypoxic tubular cell proliferation. Finally, the D-serine levels in circulation were significantly correlated with the decrease in kidney function in AKI patients. These results demonstrate the renoprotective effects of gut-derived D-serine in AKI, shed light on the interactions between the gut microbiota and the kidney in both health and AKI, and highlight D-serine as a potential new therapeutic target and biomarker for AKI.

SUBMITTER: Nakade Y

PROVIDER: S-EPMC6237464 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Gut microbiota-derived D-serine protects against acute kidney injury.

Nakade Yusuke Y Iwata Yasunori Y Furuichi Kengo K Mita Masashi M Hamase Kenji K Konno Ryuichi R Miyake Taito T Sakai Norihiko N Kitajima Shinji S Toyama Tadashi T Shinozaki Yasuyuki Y Sagara Akihiro A Miyagawa Taro T Hara Akinori A Shimizu Miho M Kamikawa Yasutaka Y Sato Kouichi K Oshima Megumi M Yoneda-Nakagawa Shiori S Yamamura Yuta Y Kaneko Shuichi S Miyamoto Tetsuya T Katane Masumi M Homma Hiroshi H Morita Hidetoshi H Suda Wataru W Hattori Masahira M Wada Takashi T

JCI insight 20181018 20

Gut microbiota-derived metabolites play important roles in health and disease. D-amino acids and their L-forms are metabolites of gut microbiota with distinct functions. In this study, we show the pathophysiologic role of D-amino acids in association with gut microbiota in humans and mice with acute kidney injury (AKI). In a mouse kidney ischemia/reperfusion model, the gut microbiota protected against tubular injury. AKI-induced gut dysbiosis contributed to the altered metabolism of D-amino acid ...[more]

PMID: 30333299

Similar Datasets

Project description:BackgroundInterleukin-17C (IL-17C), a member of the IL-17 cytokine family, plays a pathogenic role in kidney diseases. Our previous studies have shown that pre-administration of IL-17C neutralizing antibody attenuated acute kidney injury (AKI, a common acute inflammation associated renal disease). In this study, we explored whether post-ischemia reperfusion (IR) of IL-17C blockade has therapeutic effects on AKI and whether IL-17C is involved in the pathogenesis of diabetic nephropathy (DN), a major type of chronic inflammation-associated kidney disease.Methods12-week-old male C57BL/6JGpt mice were treated with IL-17C neutralizing antibody or normal IgG control antibody at 3 h after reperfusion. Renal injury, inflammation, and oxidative stress were assessed. Additionally, we examined renal IL-17C expression in patients with DN and db/db mice and evaluated albuminuria, mesangial matrix accumulation and podocyte loss in db/db mice with IL-17C neutralization. Knockdown of NF-κB p65 using siRNA, and blocking Hypoxia-inducible factor-1α (HIF-1α) using YC-1 in mice and HIF-1α Decoy in HK2 cells were investigated to explore the possible signaling pathway involved in IL-17C regulation.FindingsWe found that delayed IL-17C neutralization had similar reno-protective effects on renal ischemia-reperfusion injury (IRI). Additionally, renal IL-17C expression was increased in patients with DN and db/db mice, while IL-17C blockade significantly attenuated DN, accompanied with blunted albuminuria, mesangial matrix accumulation, and podocyte loss. Moreover, IL-17C neutralization significantly repressed the expression of downstream pro-inflammatory cytokines, inflammatory cell infiltration, and Th17/IL-17A activation both in mice with renal IRI and DN. Mechanistical studies demonstrated that hypoxia or high glucose-induced IL-17C up-regulation was predominantly mediated by NF-κB pathway.InterpretationIL-17C participates in the pathogenesis of AKI and DN and inhibition of IL-17C shows potential as a therapeutic strategy for AKI and DN.FundingThe National Natural Science Foundation of China (81770741, 81700601 and 81870504).

Dataset Information

Gut microbiota-derived D-serine protects against acute kidney injury.

Publications

Gut microbiota-derived D-serine protects against acute kidney injury.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets