Frontiers in immunology · 2025
Akkermansia muciniphila and its culture supernatant ameliorate colitis in interleukin-10 knockout mice via gut barrier and immune modulation.
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Jiang Mingshan, Jia Yongbin, Ma Chunxiang, Zeng Zhen, Li Yan, Li Lili, Lin Hao, Pang Jiangmei, Li Jiaxin, Chen Jingjing, Li Xi, Chen Kexin, Zhang Hong, Gan Yu, Xiang Zou, Chen Linlin, Zhang Hu
Аннотация
BACKGROUND: Akkermansia muciniphila (A. muciniphila) is a mucin-degrading commensal bacterium with established roles in maintaining intestinal homeostasis and modulating host immune responses. However, its therapeutic potential and mechanisms in chronic spontaneous colitis remain incompletely defined. Interleukin-10 knockout (IL-10-/-) mice are a well-established model of spontaneous colitis due to impaired anti-inflammatory cytokine signaling and disrupted immune regulation. In this study, we aimed to determine whether A. muciniphila and its culture-derived supernatant could ameliorate intestinal inflammation in IL-10-/- mice.
METHODS: We administered A. muciniphila or its culture supernatant (A. muciniphila supernatant [A.m-SN]) to IL-10-/- mice and monitored disease progression over 30 days. Clinical assessments included body weight, disease activity index (DAI), colon length, histopathology, and endoscopy. Tight junction proteins (zonula occludens-1 [ZO-1] and Occludin) and colonic messenger ribonucleic acid levels of pro- and anti-inflammatory cytokines were evaluated. Gut microbiota composition was assessed using 16S ribosomal deoxyribonucleic acid sequencing, and untargeted metabolomic profiling was performed on the culture medium to identify potential anti-inflammatory components.
RESULTS: Mice treated with A. muciniphila or A.m-SN showed significantly reduced colitis severity, including reduced body weight loss, lower DAI, preserved colon length, and improved histological scores. Immunofluorescence revealed increased expression of ZO-1 and Occludin in colonic tissues. Pro-inflammatory cytokines (tumor necrosis factor-α, IL-6, IL-17, IL-1β, and interferon-γ) were downregulated, while anti-inflammatory cytokines (IL-4, transforming growth factor-β, and IL-22) were upregulated in treated groups. Gut microbiota analysis showed partial restoration of microbial diversity and structure. Metabolomic profiling identified distinct signatures in A.m-SN, with bioactive molecules such as adenosine and tryptophan derivatives implicated in the anti-inflammatory effects.
CONCLUSION: The culture supernatant of A. muciniphila alleviated spontaneous colitis in IL-10-/- mice by suppressing pro-inflammatory cytokines, enhancing anti-inflammatory mediators, and strengthening epithelial barrier function. Metabolomic profiling identified candidate bioactive components, including adenosine and tryptophan derivatives, supporting its potential as a postbiotic intervention for inflammatory bowel disease.
METHODS: We administered A. muciniphila or its culture supernatant (A. muciniphila supernatant [A.m-SN]) to IL-10-/- mice and monitored disease progression over 30 days. Clinical assessments included body weight, disease activity index (DAI), colon length, histopathology, and endoscopy. Tight junction proteins (zonula occludens-1 [ZO-1] and Occludin) and colonic messenger ribonucleic acid levels of pro- and anti-inflammatory cytokines were evaluated. Gut microbiota composition was assessed using 16S ribosomal deoxyribonucleic acid sequencing, and untargeted metabolomic profiling was performed on the culture medium to identify potential anti-inflammatory components.
RESULTS: Mice treated with A. muciniphila or A.m-SN showed significantly reduced colitis severity, including reduced body weight loss, lower DAI, preserved colon length, and improved histological scores. Immunofluorescence revealed increased expression of ZO-1 and Occludin in colonic tissues. Pro-inflammatory cytokines (tumor necrosis factor-α, IL-6, IL-17, IL-1β, and interferon-γ) were downregulated, while anti-inflammatory cytokines (IL-4, transforming growth factor-β, and IL-22) were upregulated in treated groups. Gut microbiota analysis showed partial restoration of microbial diversity and structure. Metabolomic profiling identified distinct signatures in A.m-SN, with bioactive molecules such as adenosine and tryptophan derivatives implicated in the anti-inflammatory effects.
CONCLUSION: The culture supernatant of A. muciniphila alleviated spontaneous colitis in IL-10-/- mice by suppressing pro-inflammatory cytokines, enhancing anti-inflammatory mediators, and strengthening epithelial barrier function. Metabolomic profiling identified candidate bioactive components, including adenosine and tryptophan derivatives, supporting its potential as a postbiotic intervention for inflammatory bowel disease.