Akkermansia muciniphila identified as key strain to alleviate gut barrier injury through Wnt signaling pathway
As the largest mucosal surface, the gut has built a physical, chemical, microbial, and immune barrier to protect the body against pathogen invasion. The disturbance of gut microbiota aggravates pathogenic bacteria invasion and gut barrier injury. Fecal microbiota transplantation (FMT) is a promising...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2025-02-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/92906 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832086530738356224 |
|---|---|
| author | Xin Ma Meng Li Yuanyuan Zhang Tingting Xu Xinchen Zhou Mengqi Qian Zhiren Yang Xinyan Han |
| author_facet | Xin Ma Meng Li Yuanyuan Zhang Tingting Xu Xinchen Zhou Mengqi Qian Zhiren Yang Xinyan Han |
| author_sort | Xin Ma |
| collection | DOAJ |
| description | As the largest mucosal surface, the gut has built a physical, chemical, microbial, and immune barrier to protect the body against pathogen invasion. The disturbance of gut microbiota aggravates pathogenic bacteria invasion and gut barrier injury. Fecal microbiota transplantation (FMT) is a promising treatment for microbiome-related disorders, where beneficial strain engraftment is a significant factor influencing FMT outcomes. The aim of this research was to explore the effect of FMT on antibiotic-induced microbiome-disordered (AIMD) models infected with enterotoxigenic Escherichia coli (ETEC). We used piglet, mouse, and intestinal organoid models to explore the protective effects and mechanisms of FMT on ETEC infection. The results showed that FMT regulated gut microbiota and enhanced the protection of AIMD piglets against ETEC K88 challenge, as demonstrated by reduced intestinal pathogen colonization and alleviated gut barrier injury. Akkermansia muciniphila (A. muciniphila) and Bacteroides fragilis (B. fragilis) were identified as two strains that may play key roles in FMT. We further investigated the alleviatory effects of these two strains on ETEC infection in the AIMD mice model, which revealed that A. muciniphila and B. fragilis relieved ETEC-induced intestinal inflammation by maintaining the proportion of Treg/Th17 cells and epithelial damage by moderately activating the Wnt/β-catenin signaling pathway, while the effect of A. muciniphila was better than B. fragilis. We, therefore, identified whether A. muciniphila protected against ETEC infection using basal-out and apical-out intestinal organoid models. A. muciniphila did protect the intestinal stem cells and stimulate the proliferation and differentiation of intestinal epithelium, and the protective effects of A. muciniphila were reversed by Wnt inhibitor. FMT alleviated ETEC-induced gut barrier injury and intestinal inflammation in the AIMD model. A. muciniphila was identified as a key strain in FMT to promote the proliferation and differentiation of intestinal stem cells by mediating the Wnt/β-catenin signaling pathway. |
| format | Article |
| id | doaj-art-b150605eed794c16852786ece227aa58 |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-b150605eed794c16852786ece227aa582025-02-06T14:33:05ZengeLife Sciences Publications LtdeLife2050-084X2025-02-011210.7554/eLife.92906Akkermansia muciniphila identified as key strain to alleviate gut barrier injury through Wnt signaling pathwayXin Ma0Meng Li1Yuanyuan Zhang2Tingting Xu3Xinchen Zhou4Mengqi Qian5Zhiren Yang6Xinyan Han7https://orcid.org/0000-0001-7044-7439Key Laboratory of Animal Nutrition and Feed Science in East China, Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, China; Hainan Institute of Zhejiang University, Yongyou Industry Park, Yazhou Bay Sci-Tech City, Sanya, ChinaKey Laboratory of Animal Nutrition and Feed Science in East China, Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, China; Hainan Institute of Zhejiang University, Yongyou Industry Park, Yazhou Bay Sci-Tech City, Sanya, ChinaKey Laboratory of Animal Nutrition and Feed Science in East China, Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, ChinaKey Laboratory of Animal Nutrition and Feed Science in East China, Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, ChinaKey Laboratory of Animal Nutrition and Feed Science in East China, Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, China; Hainan Institute of Zhejiang University, Yongyou Industry Park, Yazhou Bay Sci-Tech City, Sanya, ChinaKey Laboratory of Animal Nutrition and Feed Science in East China, Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, ChinaKey Laboratory of Animal Nutrition and Feed Science in East China, Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, China; Hainan Institute of Zhejiang University, Yongyou Industry Park, Yazhou Bay Sci-Tech City, Sanya, ChinaKey Laboratory of Animal Nutrition and Feed Science in East China, Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, China; Hainan Institute of Zhejiang University, Yongyou Industry Park, Yazhou Bay Sci-Tech City, Sanya, ChinaAs the largest mucosal surface, the gut has built a physical, chemical, microbial, and immune barrier to protect the body against pathogen invasion. The disturbance of gut microbiota aggravates pathogenic bacteria invasion and gut barrier injury. Fecal microbiota transplantation (FMT) is a promising treatment for microbiome-related disorders, where beneficial strain engraftment is a significant factor influencing FMT outcomes. The aim of this research was to explore the effect of FMT on antibiotic-induced microbiome-disordered (AIMD) models infected with enterotoxigenic Escherichia coli (ETEC). We used piglet, mouse, and intestinal organoid models to explore the protective effects and mechanisms of FMT on ETEC infection. The results showed that FMT regulated gut microbiota and enhanced the protection of AIMD piglets against ETEC K88 challenge, as demonstrated by reduced intestinal pathogen colonization and alleviated gut barrier injury. Akkermansia muciniphila (A. muciniphila) and Bacteroides fragilis (B. fragilis) were identified as two strains that may play key roles in FMT. We further investigated the alleviatory effects of these two strains on ETEC infection in the AIMD mice model, which revealed that A. muciniphila and B. fragilis relieved ETEC-induced intestinal inflammation by maintaining the proportion of Treg/Th17 cells and epithelial damage by moderately activating the Wnt/β-catenin signaling pathway, while the effect of A. muciniphila was better than B. fragilis. We, therefore, identified whether A. muciniphila protected against ETEC infection using basal-out and apical-out intestinal organoid models. A. muciniphila did protect the intestinal stem cells and stimulate the proliferation and differentiation of intestinal epithelium, and the protective effects of A. muciniphila were reversed by Wnt inhibitor. FMT alleviated ETEC-induced gut barrier injury and intestinal inflammation in the AIMD model. A. muciniphila was identified as a key strain in FMT to promote the proliferation and differentiation of intestinal stem cells by mediating the Wnt/β-catenin signaling pathway.https://elifesciences.org/articles/92906pigmouseorganoid |
| spellingShingle | Xin Ma Meng Li Yuanyuan Zhang Tingting Xu Xinchen Zhou Mengqi Qian Zhiren Yang Xinyan Han Akkermansia muciniphila identified as key strain to alleviate gut barrier injury through Wnt signaling pathway eLife pig mouse organoid |
| title | Akkermansia muciniphila identified as key strain to alleviate gut barrier injury through Wnt signaling pathway |
| title_full | Akkermansia muciniphila identified as key strain to alleviate gut barrier injury through Wnt signaling pathway |
| title_fullStr | Akkermansia muciniphila identified as key strain to alleviate gut barrier injury through Wnt signaling pathway |
| title_full_unstemmed | Akkermansia muciniphila identified as key strain to alleviate gut barrier injury through Wnt signaling pathway |
| title_short | Akkermansia muciniphila identified as key strain to alleviate gut barrier injury through Wnt signaling pathway |
| title_sort | akkermansia muciniphila identified as key strain to alleviate gut barrier injury through wnt signaling pathway |
| topic | pig mouse organoid |
| url | https://elifesciences.org/articles/92906 |
| work_keys_str_mv | AT xinma akkermansiamuciniphilaidentifiedaskeystraintoalleviategutbarrierinjurythroughwntsignalingpathway AT mengli akkermansiamuciniphilaidentifiedaskeystraintoalleviategutbarrierinjurythroughwntsignalingpathway AT yuanyuanzhang akkermansiamuciniphilaidentifiedaskeystraintoalleviategutbarrierinjurythroughwntsignalingpathway AT tingtingxu akkermansiamuciniphilaidentifiedaskeystraintoalleviategutbarrierinjurythroughwntsignalingpathway AT xinchenzhou akkermansiamuciniphilaidentifiedaskeystraintoalleviategutbarrierinjurythroughwntsignalingpathway AT mengqiqian akkermansiamuciniphilaidentifiedaskeystraintoalleviategutbarrierinjurythroughwntsignalingpathway AT zhirenyang akkermansiamuciniphilaidentifiedaskeystraintoalleviategutbarrierinjurythroughwntsignalingpathway AT xinyanhan akkermansiamuciniphilaidentifiedaskeystraintoalleviategutbarrierinjurythroughwntsignalingpathway |