Effects of Abrus cantoniensis capsule on gut microbiota and intestinal barrier in mice infected with alveolar echinococcosis.

BACKGROUND: Alveolar echinococcosis (AE) is a progressive parasitic disease characterized by tumor-like invasiveness, with liver fibrosis being a primary pathological feature. This study was conducted to evaluate the therapeutic effects of Abrus cantoniensis capsule (ACC) on the gut microbiota and intestinal barrier in an experimental mouse model with AE infection; to identify potential therapeutic targets by integrating traditional Chinese medicine (TCM) pharmacological network analysis with molecular docking validation, so as to lay a theoretical foundation for the clinical application of TCM in AE treatment.

METHODS: Our experiment investigated the therapeutic effects of ACC in two aspects: (1) To analyze the effect of the ACC aqueous solution on protoscolices, protoscolices were isolated from AE cysts and cultured under the conditions of ACC, with albendazole (ABZ, positive control) separately or jointly used. (2) Thirty mice were randomly divided into five groups and subjected to treatment for 8 weeks to comprehensively analyze liver fibrosis, serum cytokine profiles, intestinal integrity, and microbiota composition. Additionally, potential therapeutic targets were validated by integrating network pharmacology with molecular docking.

RESULTS: 1) ACC exhibited an inhibitory effect on protoscolices comparable to that of ABZ (p < 0.05). 2) ACC alleviated liver fibrosis in AE-infected mice, with significant decrease in the levels of ALT, TNF-α and IL-6 (all p < 0.05), suggesting a potential anti-inflammatory response mediated by immune activation and a hepatoprotective effect. 3) ACC treatment preserved villus morphology, maintained mucin secretion, and significantly increased Paneth cell density (all p < 0.01). Mechanistically, it might be attributed to upregulated levels of tight junction proteins (ZO-1, and Occludin) and antimicrobial effectors (MUC2, and Lysozyme), as well as reduced intestinal permeability. 4) 16S rRNA sequencing revealed that ACC could obviously restore the abundance of Ligilactobacillus, with a 4.5-fold increase compared to AE, which was consistent with the results of redundancy analysis, where the abundance of Ligilactobacillus exhibited negative correlations with ALT and IL-6 levels.

CONCLUSION: ACC can enrich Ligilactobacillus to modulate the gut microbiota, and protect intestinal mucosal integrity, thereby reducing the translocation of endotoxins to the liver and alleviating liver fibrosis eventually.