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Nat. Commun., Apr 06 2024, 15 (1) | https://doi.org/10.1038/s41467-024-47275-8 The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation

Eun-Jung Kang ^1,2,17, Jae-Hoon Kim ^1,3,17, Young Eun Kim ^4,5,17, Hana Lee ⁶, Kwang Bo Jung ⁶, Dong-Ho Chang ⁷, Youngjin Lee ⁷, Shinhye Park ⁷, Eun-Young Lee ⁷, Eun-Ji Lee ⁸, Ho Bum Kang ⁹, Moon-Young Rhyoo ¹⁰, Seungwoo Seo ⁵, Sohee Park ^6,11, Yubin Huh ^6,11, Jun Go ¹, Jung Hyeon Choi ¹, Young-Keun Choi ¹, In-Bok Lee ¹, Dong-Hee Choi ¹, Yun Jeong Seo ¹, Jung-Ran Noh ¹, Kyoung-Shim Kim ^1,12, Jung Hwan Hwang ^1,12, Ji-Seon Jeong ^4,13, Ha-Jeong Kwon ⁴, Hee Min Yoo^4,13, Mi-Young Son ^6,11, Yeon-Gu Kim ^8,14, Dae-Hee Lee ^9,15, Tae-Young Kim ⁵, Hyo-Jung Kwon ², Myung Hee Kim ⁷, Byoung-Chan Kim ^7,16, Yong-Hoon Kim ^1,12,*, Dukjin Kang ^4,* & Chul-Ho Lee ^1,12,*

¹Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
²Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Republic of Korea.
³Livestock Products Analysis Division, Division of Animal health, Daejeon Metropolitan City Institute of Health and Environment, Daejeon 34146, Republic of Korea.
⁴Group for Biometrology, Korea Research Institute of Standards and Science (KRISS), Daejeon 34113, Republic of Korea.
⁵School of Earth Sciences & Environmental Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea.
⁶Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
⁷Microbiome Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
⁸Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
⁹Synthetic Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
¹⁰Laboratory Animal Resource Center, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
¹¹Department of Bio-Molecular Science, Korea Research Institute of Bioscience and Biotechnology (KRIBB) School of Bioscience, Korea University of Science and Technology (UST), Daejeon 34141, Republic of Korea.
¹²Department of Functional Genomics, Korea Research Institute of Bioscience and Biotechnology (KRIBB) School of Bioscience, Korea University of Science and Technology (UST), Daejeon 34141, Republic of Korea.
¹³Department of Measurement Science, Korea Research Institute of Standards and Science (KRISS) School of Precision Measurement, Korea University of Science and Technology (UST), Daejeon 34113, Republic of Korea.
¹⁴Department of Applied Biological Engineering, Korea Research Institute of Bioscience and Biotechnology (KRIBB) School of Biotechnology, University of Science and Technology (UST), Daejeon 34141, Republic of Korea.
¹⁵Department of Biosystems and Bioengineering, Korea Research Institute of Bioscience and Biotechnology (KRIBB) School of Biotechnology, University of Science and Technology (UST), Daejeon 34141, Republic of Korea.
¹⁶HealthBiome Inc., Daejeon 34141, Republic of Korea.
¹⁷These authors contributed equally: Eun-Jung Kang, Jae-Hoon Kim, Young Eun Kim.

^*Corresponding authors: correspondence to Yong-Hoon Kim, Dukjin Kang or Chul-Ho Lee

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.

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형식Research article
게재일2024년 04월 (BRIC 등록일 2024-05-08)
연구진국내 연구진
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