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

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, Sohee Park, Yubin Huh, Jun Go, Jung Hyeon Choi, Young-Keun Choi, In-Bok Lee, Dong-Hee Choi, Yun Jeong Seo, Jung-Ran Noh, Kyoung-Shim Kim, Jung Hwan Hwang, Ji-Seon Jeong, Ha-Jeong Kwon, Hee Min Yoo, Mi-Young Son, Yeon-Gu Kim, Dae-Hee Lee, Tae-Young Kim, Hyo-Jung Kwon, Myung Hee Kim, Byoung-Chan Kim, Yong-Hoon Kim (), Dukjin Kang () and Chul-Ho Lee ()
Additional contact information
Eun-Jung Kang: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Jae-Hoon Kim: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Young Eun Kim: Korea Research Institute of Standards and Science (KRISS)
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)
Yubin Huh: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
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)
Jung Hwan Hwang: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Ji-Seon Jeong: Korea Research Institute of Standards and Science (KRISS)
Ha-Jeong Kwon: Korea Research Institute of Standards and Science (KRISS)
Hee Min Yoo: Korea Research Institute of Standards and Science (KRISS)
Mi-Young Son: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Yeon-Gu Kim: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Dae-Hee Lee: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
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)
Yong-Hoon Kim: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Dukjin Kang: Korea Research Institute of Standards and Science (KRISS)
Chul-Ho Lee: Korea Research Institute of Bioscience and Biotechnology (KRIBB)

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-47275-8

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