微囊藻毒素 (MC) 是蓝藻产生的毒素，微囊藻毒素-LR (MC-LR) 是水生环境中最普遍、最具毒性的变体之一。 MC-LR不仅造成环境问题，而且对人类健康构成重大风险。本研究旨在探讨 MC-LR 对 APCmin/ 小鼠的影响，APCmin/小鼠被认为是肠道肿瘤的理想动物模型。我们给小鼠灌胃 40 µg/kg MC-LR 8 周，然后进行组织病理学检查、微生物多样性和代谢组学分析。与对照组相比，暴露于 MC-LR 的小鼠在 APCmin/ 小鼠中表现出结直肠癌进展的显着促进和肠道屏障功能受损。在暴露于 MC-LR 的小鼠中观察到肠道微生物失调，表明肠道微生物群结构发生显着改变。这包括 Marvinbryantia、Gordonibacter 和 Family_XIII_AD3011_group 的富集以及 Faecalibaculum 和 Lachnoclostridium 的减少。代谢组学分析显示，暴露于 MC-LR 的小鼠肠道内容物中胆汁酸 (BA) 代谢物增加，特别是牛磺胆酸 (TCA)、α-鼠胆酸 (α-MCA)、3-脱氢胆酸 (3-DHCA)、 7-酮脱氧胆酸（7-KDCA）和12-酮脱氧胆酸（12-KDCA）。此外，我们发现在暴露于 MC-LR 的小鼠中，Marvinbryantia 和 Family_XIII_AD3011_group 与牛磺胆酸 (TCA) 表现出最强的正相关性。这些发现为MC-LR在易感人群中的作用和机制提供了新的见解，为MC-LR在饮用水中的指导价值提供了基础。

Microcystins (MCs), toxins generated by cyanobacteria, feature microcystin-LR (MC-LR) as one of the most prevalent and toxic variants in aquatic environments. MC-LR not only causes environmental problems but also presents a substantial risk to human health. This study aimed to investigate the impact of MC-LR on APCmin/+ mice, considered as an ideal animal model for intestinal tumors. We administered 40 µg/kg MC-LR to mice by gavage for 8 weeks, followed by histopathological examination, microbial diversity and metabolomics analysis. The mice exposed to MC-LR exhibited a significant promotion in colorectal cancer progression and impaired intestinal barrier function in the APCmin/+ mice compared with the control. Gut microbial dysbiosis was observed in the MC-LR-exposed mice, manifesting a notable alteration in the structure of the gut microbiota. This included the enrichment of Marvinbryantia, Gordonibacter and Family_XIII_AD3011_group and reductions in Faecalibaculum and Lachnoclostridium. Metabolomics analysis revealed increased bile acid (BA) metabolites in the intestinal contents of the mice exposed to MC-LR, particularly taurocholic acid (TCA), alpha-muricholic acid (α-MCA), 3-dehydrocholic acid (3-DHCA), 7-ketodeoxycholic acid (7-KDCA) and 12-ketodeoxycholic acid (12-KDCA). Moreover, we found that Marvinbryantia and Family_XIII_AD3011_group showed the strongest positive correlation with taurocholic acid (TCA) in the mice exposed to MC-LR. These findings provide new insights into the roles and mechanisms of MC-LR in susceptible populations, providing a basis for guiding values of MC-LR in drinking water.