Stable colonization of Akkermansia muciniphila educates host intestinal microecology and immunity to battle against inflammatory intestinal diseases

• Published in: Experimental & molecular medicine Vol. 55; no. 1; pp. 55 - 68
• Main Authors: Wang, Bin, Chen, Xuheng, Chen, Zhiyuan, Xiao, Huiwen, Dong, Jiali, Li, Yuan, Zeng, Xiaozhou, Liu, Jinjian, Wan, Guoyun, Fan, Saijun, Cui, Ming
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-01-2023; Springer Nature B.V; 생화학분자생물학회
• Subjects: 13/21; 13/51; 38/77; 38/90; 45/23; 59/5; 631/154/152; 631/1647/350/354; 64/60; 692/699/1503/257/1389; 692/699/1503/2745; Akkermansia muciniphila; Animal models; Animals; Biomedical and Life Sciences; Biomedicine; Colitis; Colitis - chemically induced; Colonization; Community structure; Dextran; Digestive system; Gastrointestinal Microbiome - physiology; Gastrointestinal tract; Gene expression; Inflammatory bowel disease; Inflammatory Bowel Diseases; Interleukin 4; Intestine; Iron oxides; Lactobacillus; Macrophages; Mannose; Medical Biochemistry; Medical personnel; Mice; Molecular Medicine; Nanoparticles; Probiotics; Sodium sulfate; Stem Cells; Toxicity; Verrucomicrobia - metabolism; 생화학
• ISSN: 2092-6413; 1226-3613; 2092-6413
• DOI: 10.1038/s12276-022-00911-z

Gut microbial preparations are widely used in treating intestinal diseases but show mixed success. In this study, we found that the therapeutic efficacy of
A. muciniphila
for dextran sodium sulfate (DSS)-induced colitis as well as intestinal radiation toxicity was ~50%, and mice experiencing a positive prognosis harbored a high frequency of
A. muciniphila
in the gastrointestinal (GI) tract. Stable GI colonization of
A. muciniphila
elicited more profound shifts in the gut microbial community structure of hosts. Coexisting with
A. muciniphila
facilitated proliferation and reprogrammed the gene expression profile of
Lactobacillus murinus
, a classic probiotic that overtly responded to
A. muciniphila
addition in a time-dependent manner. Then, a magnetic-drove, mannose-loaded nanophase material was designed and linked to the surface of
A. muciniphila
. The modified
A. muciniphila
exhibited enhancements in inflammation targeting and intestinal colonization under an external magnetic field, elevating the positive-response rate and therapeutic efficacy against intestinal diseases. However, the unlinked cocktail containing
A. muciniphila
and the delivery system only induced negligible improvement of therapeutic efficacy. Importantly, heat-inactivated
A. muciniphila
lost therapeutic effects on DSS-induced colitis and was even retained in the GI tract for a long time. Further investigations revealed that the modified
A. muciniphila
was able to drive M2 macrophage polarization by upregulating the protein level of IL-4 at inflammatory loci. Together, our findings demonstrate that stable colonization of live
A. muciniphila
at lesion sites is essential for its anti-inflammatory function.
Inflammatory bowel disease: Magnets help modified bacteria colonize the gut
A modified gut bacterium that can colonize the gut more effectively with the help of magnets could offer a novel treatment for inflammatory bowel diseases (IBD). In experiments on mouse models, Ming Cui at the Chinese Academy of Medical Sciences and Peking Union Medical College, China, and co-workers showed that when the bacterium
Akkermansia muciniphila
successfully colonizes the gut it repairs damage caused by IBD and boosts the proliferation of another probiotic bacterium,
Lactobacillus murinus
. To enhance colonization chances, the team added Fe
3
O
4
nanoparticles to the bacterium as well as mannose, a sugar monomer that is drawn to the macrophages present in inflamed regions. The magnetic
A. muciniphila
was then attracted to the correct part of the gut and held in place using magnets on the skin. Initial experiments suggest that this safely enhances stable colonization.