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The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation

Author

Listed:
  • Eun-Jung Kang

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Chungnam National University)

  • Jae-Hoon Kim

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Daejeon Metropolitan City Institute of Health and Environment)

  • Young Eun Kim

    (Korea Research Institute of Standards and Science (KRISS)
    Gwangju Institute of Science and Technology (GIST))

  • Hana Lee

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Kwang Bo Jung

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Dong-Ho Chang

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Youngjin Lee

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Shinhye Park

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Eun-Young Lee

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Eun-Ji Lee

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Ho Bum Kang

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Moon-Young Rhyoo

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Seungwoo Seo

    (Gwangju Institute of Science and Technology (GIST))

  • Sohee Park

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Yubin Huh

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Jun Go

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Jung Hyeon Choi

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Young-Keun Choi

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • In-Bok Lee

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Dong-Hee Choi

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Yun Jeong Seo

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Jung-Ran Noh

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Kyoung-Shim Kim

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Jung Hwan Hwang

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Ji-Seon Jeong

    (Korea Research Institute of Standards and Science (KRISS)
    Korea University of Science and Technology (UST))

  • Ha-Jeong Kwon

    (Korea Research Institute of Standards and Science (KRISS))

  • Hee Min Yoo

    (Korea Research Institute of Standards and Science (KRISS)
    Korea University of Science and Technology (UST))

  • Mi-Young Son

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Yeon-Gu Kim

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    University of Science and Technology (UST))

  • Dae-Hee Lee

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    University of Science and Technology (UST))

  • Tae-Young Kim

    (Gwangju Institute of Science and Technology (GIST))

  • Hyo-Jung Kwon

    (Chungnam National University)

  • Myung Hee Kim

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB))

  • Byoung-Chan Kim

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    HealthBiome Inc.)

  • Yong-Hoon Kim

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

  • Dukjin Kang

    (Korea Research Institute of Standards and Science (KRISS))

  • Chul-Ho Lee

    (Korea Research Institute of Bioscience and Biotechnology (KRIBB)
    Korea University of Science and Technology (UST))

Abstract

Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/β-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/β-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health.

Suggested Citation

  • Eun-Jung Kang & Jae-Hoon Kim & Young Eun Kim & Hana Lee & Kwang Bo Jung & Dong-Ho Chang & Youngjin Lee & Shinhye Park & Eun-Young Lee & Eun-Ji Lee & Ho Bum Kang & Moon-Young Rhyoo & Seungwoo Seo & Soh, 2024. "The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47275-8
    DOI: 10.1038/s41467-024-47275-8
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    References listed on IDEAS

    as
    1. Nalle Pentinmikko & Sharif Iqbal & Miyeko Mana & Simon Andersson & Armand B. Cognetta & Radu M. Suciu & Jatin Roper & Kalle Luopajärvi & Eino Markelin & Swetha Gopalakrishnan & Olli-Pekka Smolander & , 2019. "Notum produced by Paneth cells attenuates regeneration of aged intestinal epithelium," Nature, Nature, vol. 571(7765), pages 398-402, July.
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