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Updated: Jan 8, 2026

Three-dimensional Quantification of Intestinal Mucus Using Whole-mount Tissue Imaging
Published on: September 12, 2025
Akkermansia muciniphila outer membrane protein Amuc_0904 modulates intestinal homeostasis by promoting goblet cell
Liu Yang1, Jianming Yang1, Xueting Kong1
1Tianjin Institute of Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), School of Basic Medical Sciences, Tianjin Medical University, State Key Laboratory of Experimental Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China.
Abstract:
Akkermansia muciniphila is recognized as a promising probiotic that improves the symptoms of a variety of diseases. However, the role and mechanism of A. muciniphila in regulating intestinal homeostasis remain to be explored. Here, we discovered that A. muciniphila was dramatically increased during colitis recovery, and its colonization greatly increased goblet cells to protect the intestinal barrier in mice. Amuc_0904, a previously uncharacterized A. muciniphila outer membrane protein, was identified to induce goblet cell differentiation. Mechanistically, Amuc_0904 directly interacted with MET and decreased its phosphorylation in epithelia, leading to decreased Wnt/β-catenin signaling and enhanced oxidative phosphorylation and mitochondrial function. Furthermore, Amuc_0904 and engineered probiotic Escherichia coli Nissle 1917 expressing Amuc_0904 were demonstrated to protect mice from colitis and colitis-associated colorectal cancer. The study reveals a previously unknown mechanism of A. muciniphila-mediated intestinal homeostasis recovery and provides a bioactive molecule with the potential to treat intestinal disorders.
Insights
Akkermansia muciniphila, a beneficial gut bacterium, aids intestinal recovery by increasing goblet cells. Its outer membrane protein Amuc_0904 promotes gut barrier function and protects against colitis.
Area of Science:
- Microbiology
- Gastroenterology
- Immunology
Background:
- Akkermansia muciniphila is a promising probiotic with therapeutic potential.
- Its precise mechanisms in maintaining intestinal homeostasis are not fully understood.
Purpose of the Study:
- To investigate the role and mechanism of A. muciniphila in regulating intestinal homeostasis.
- To identify specific molecules involved in A. muciniphila-mediated gut protection.
Main Methods:
- Studied A. muciniphila colonization during colitis recovery in mice.
- Identified and characterized the outer membrane protein Amuc_0904.
- Investigated Amuc_0904's interaction with host cell signaling pathways (MET, Wnt/β-catenin).
- Assessed the protective effects of Amuc_0904 and engineered probiotics in colitis models.
Main Results:
- A. muciniphila abundance increased significantly during colitis recovery.
- Amuc_0904 induced goblet cell differentiation, enhancing intestinal barrier integrity.
- Amuc_0904 modulated MET signaling, reducing Wnt/β-catenin activity and improving mitochondrial function.
- Amuc_0904 conferred protection against colitis and colitis-associated colorectal cancer in mice.
Conclusions:
- A. muciniphila promotes intestinal homeostasis recovery through Amuc_0904-mediated goblet cell induction and barrier protection.
- Amuc_0904 represents a novel therapeutic target for intestinal disorders.
- Engineered probiotics expressing Amuc_0904 show potential for treating inflammatory bowel disease and associated cancers.
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