The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation
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 wel...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-04-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-47275-8 |
| _version_ | 1827291449872351232 |
|---|---|
| author | 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 Chul-Ho Lee |
| author_facet | 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 Chul-Ho Lee |
| author_sort | Eun-Jung Kang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T12:38:18Z |
| format | Article |
| id | doaj.art-561797eb415d4717ac55e900e1272c33 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T12:38:18Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-561797eb415d4717ac55e900e1272c332024-04-07T11:22:49ZengNature PortfolioNature Communications2041-17232024-04-0115112010.1038/s41467-024-47275-8The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulationEun-Jung Kang0Jae-Hoon Kim1Young Eun Kim2Hana Lee3Kwang Bo Jung4Dong-Ho Chang5Youngjin Lee6Shinhye Park7Eun-Young Lee8Eun-Ji Lee9Ho Bum Kang10Moon-Young Rhyoo11Seungwoo Seo12Sohee Park13Yubin Huh14Jun Go15Jung Hyeon Choi16Young-Keun Choi17In-Bok Lee18Dong-Hee Choi19Yun Jeong Seo20Jung-Ran Noh21Kyoung-Shim Kim22Jung Hwan Hwang23Ji-Seon Jeong24Ha-Jeong Kwon25Hee Min Yoo26Mi-Young Son27Yeon-Gu Kim28Dae-Hee Lee29Tae-Young Kim30Hyo-Jung Kwon31Myung Hee Kim32Byoung-Chan Kim33Yong-Hoon Kim34Dukjin Kang35Chul-Ho Lee36Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Group for Biometrology, Korea Research Institute of Standards and Science (KRISS)Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Microbiome Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Microbiome Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Microbiome Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Microbiome Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Synthetic Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Laboratory Animal Resource Center, Korea Advanced Institute of Science and Technology (KAIST)School of Earth Sciences & Environmental Engineering, Gwangju Institute of Science and Technology (GIST)Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Group for Biometrology, Korea Research Institute of Standards and Science (KRISS)Group for Biometrology, Korea Research Institute of Standards and Science (KRISS)Group for Biometrology, Korea Research Institute of Standards and Science (KRISS)Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Synthetic Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)School of Earth Sciences & Environmental Engineering, Gwangju Institute of Science and Technology (GIST)Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National UniversityMicrobiome Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Microbiome Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Group for Biometrology, Korea Research Institute of Standards and Science (KRISS)Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)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.https://doi.org/10.1038/s41467-024-47275-8 |
| spellingShingle | 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 Chul-Ho Lee The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation Nature Communications |
| title | The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation |
| title_full | The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation |
| title_fullStr | The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation |
| title_full_unstemmed | The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation |
| title_short | The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation |
| title_sort | secreted protein amuc 1409 from akkermansia muciniphila improves gut health through intestinal stem cell regulation |
| url | https://doi.org/10.1038/s41467-024-47275-8 |
| work_keys_str_mv | AT eunjungkang thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT jaehoonkim thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT youngeunkim thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT hanalee thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT kwangbojung thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT donghochang thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT youngjinlee thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT shinhyepark thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT eunyounglee thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT eunjilee thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT hobumkang thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT moonyoungrhyoo thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT seungwooseo thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT soheepark thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT yubinhuh thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT jungo thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT junghyeonchoi thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT youngkeunchoi thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT inboklee thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT dongheechoi thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT yunjeongseo thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT jungrannoh thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT kyoungshimkim thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT junghwanhwang thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT jiseonjeong thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT hajeongkwon thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT heeminyoo thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT miyoungson thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT yeongukim thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT daeheelee thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT taeyoungkim thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT hyojungkwon thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT myungheekim thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT byoungchankim thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT yonghoonkim thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT dukjinkang thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT chulholee thesecretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT eunjungkang secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT jaehoonkim secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT youngeunkim secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT hanalee secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT kwangbojung secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT donghochang secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT youngjinlee secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT shinhyepark secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT eunyounglee secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT eunjilee secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT hobumkang secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT moonyoungrhyoo secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT seungwooseo secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT soheepark secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT yubinhuh secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT jungo secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT junghyeonchoi secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT youngkeunchoi secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT inboklee secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT dongheechoi secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT yunjeongseo secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT jungrannoh secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT kyoungshimkim secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT junghwanhwang secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT jiseonjeong secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT hajeongkwon secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT heeminyoo secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT miyoungson secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT yeongukim secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT daeheelee secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT taeyoungkim secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT hyojungkwon secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT myungheekim secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT byoungchankim secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT yonghoonkim secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT dukjinkang secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation AT chulholee secretedproteinamuc1409fromakkermansiamuciniphilaimprovesguthealththroughintestinalstemcellregulation |