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

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

研究成果: ジャーナルへの寄稿記事

1 引用 (Scopus)

抄録

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.

元の言語英語
ジャーナルJCI insight
3
発行部数20
DOI
出版物ステータス出版済み - 10 18 2018

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Acute Kidney Injury
Serine
Kidney
Amino Acids
Dysbiosis
D-Amino-Acid Oxidase
L Forms
Health
Wounds and Injuries
Gastrointestinal Microbiome
Reperfusion
Oral Administration
Ischemia
Biomarkers
Cell Proliferation

これを引用

Nakade, Y., Iwata, Y., Furuichi, K., Mita, M., Hamase, K., Konno, R., ... Wada, T. (2018). Gut microbiota-derived D-serine protects against acute kidney injury. JCI insight, 3(20). https://doi.org/10.1172/jci.insight.97957

Gut microbiota-derived D-serine protects against acute kidney injury. / Nakade, Yusuke; Iwata, Yasunori; Furuichi, Kengo; Mita, Masashi; Hamase, Kenji; Konno, Ryuichi; Miyake, Taito; Sakai, Norihiko; Kitajima, Shinji; Toyama, Tadashi; Shinozaki, Yasuyuki; Sagara, Akihiro; Miyagawa, Taro; Hara, Akinori; Shimizu, Miho; Kamikawa, Yasutaka; Sato, Kouichi; Oshima, Megumi; Yoneda-Nakagawa, Shiori; Yamamura, Yuta; Kaneko, Shuichi; Miyamoto, Tetsuya; Katane, Masumi; Homma, Hiroshi; Morita, Hidetoshi; Suda, Wataru; Hattori, Masahira; Wada, Takashi.

:: JCI insight, 巻 3, 番号 20, 18.10.2018.

研究成果: ジャーナルへの寄稿記事

Nakade, Y, Iwata, Y, Furuichi, K, Mita, M, Hamase, K, Konno, R, Miyake, T, Sakai, N, Kitajima, S, Toyama, T, Shinozaki, Y, Sagara, A, Miyagawa, T, Hara, A, Shimizu, M, Kamikawa, Y, Sato, K, Oshima, M, Yoneda-Nakagawa, S, Yamamura, Y, Kaneko, S, Miyamoto, T, Katane, M, Homma, H, Morita, H, Suda, W, Hattori, M & Wada, T 2018, 'Gut microbiota-derived D-serine protects against acute kidney injury', JCI insight, 巻. 3, 番号 20. https://doi.org/10.1172/jci.insight.97957
Nakade, Yusuke ; Iwata, Yasunori ; Furuichi, Kengo ; Mita, Masashi ; Hamase, Kenji ; Konno, Ryuichi ; Miyake, Taito ; Sakai, Norihiko ; Kitajima, Shinji ; Toyama, Tadashi ; Shinozaki, Yasuyuki ; Sagara, Akihiro ; Miyagawa, Taro ; Hara, Akinori ; Shimizu, Miho ; Kamikawa, Yasutaka ; Sato, Kouichi ; Oshima, Megumi ; Yoneda-Nakagawa, Shiori ; Yamamura, Yuta ; Kaneko, Shuichi ; Miyamoto, Tetsuya ; Katane, Masumi ; Homma, Hiroshi ; Morita, Hidetoshi ; Suda, Wataru ; Hattori, Masahira ; Wada, Takashi. / Gut microbiota-derived D-serine protects against acute kidney injury. :: JCI insight. 2018 ; 巻 3, 番号 20.
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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.",
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AU - Nakade, Yusuke

AU - Iwata, Yasunori

AU - Furuichi, Kengo

AU - Mita, Masashi

AU - Hamase, Kenji

AU - Konno, Ryuichi

AU - Miyake, Taito

AU - Sakai, Norihiko

AU - Kitajima, Shinji

AU - Toyama, Tadashi

AU - Shinozaki, Yasuyuki

AU - Sagara, Akihiro

AU - Miyagawa, Taro

AU - Hara, Akinori

AU - Shimizu, Miho

AU - Kamikawa, Yasutaka

AU - Sato, Kouichi

AU - Oshima, Megumi

AU - Yoneda-Nakagawa, Shiori

AU - Yamamura, Yuta

AU - Kaneko, Shuichi

AU - Miyamoto, Tetsuya

AU - Katane, Masumi

AU - Homma, Hiroshi

AU - Morita, Hidetoshi

AU - Suda, Wataru

AU - Hattori, Masahira

AU - Wada, Takashi

PY - 2018/10/18

Y1 - 2018/10/18

N2 - 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.

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