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Previous research found that Hericium erinaceus-derived peptide (Lys-Ser-Pro-Leu-Tyr, KSPLY) ameliorated intestinal barrier injury and increased the abundance of the gut bacterium Akkermansia muciniphila. To investigate the role of A.muciniphila in improving intestinal barrier damage, a barrier injury model was established using lipopolysaccharide (LPS)-induced Caco-2 cells. The cells were treated with different concentrations of A.muciniphila, its cellular components, or its metabolic products. Untargeted metabolomics was employed to analyze metabolite profiles, cell viability was assessed by the CCK-8 assay, and mRNA expression levels of mucin-related factors, inflammatory cytokines, apoptosis-related factors, and key MAPK signaling pathway proteins were measured using quantitative real-time PCR. Compared to the LPS group, significant upregulation of Muc2 mRNA relative expression was observed by 16.75% and 11.57% after treatment with A.muciniphila at 107 and 105 CFU/mL, respectively, while TFF3 mRNA relative expression was increased by 12.38% and 9.71%. Treatment with the A.muciniphila cell wall resulted in an 18.71% increase in Muc2 mRNA relative expression and a 13.28% increase in TFF3 mRNA relative expression. The major metabolites of A.muciniphila—L-aspartic acid, L-histidine, citric acid, and kynurenic acid—were found to enhance Muc2 mRNA relative expression by 18.09%, 20.29%, 23.67%, and 18.61%, respectively, and TFF3 mRNA relative expression by 10.22%, 10.21%, 10.29%, and 10.98%. Furthermore, the mRNA relative expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8), pro-apoptotic factors (Bax, Caspase-3, Caspase-8), pro-apoptotic proteins (p21, p27), and key MAPK pathway components (p38, JNK, ERK) was significantly downregulated by A.muciniphila, its cell wall, and its key metabolites. In conclusion, A.muciniphila and its cell wall components and primary metabolites can alleviate intestinal barrier injury, likely by inhibiting the activation of the MAPK signaling pathway. This study provides a theoretical basis for understanding the active substances and mechanisms by which A.muciniphila improves intestinal barrier damage.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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