PDF(Pubmed)
Abstract：
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.
摘要：
微囊藻毒素（MC），蓝细菌产生的毒素，微囊藻毒素-LR（MC-LR）是水生环境中最普遍和有毒的变种之一。MC-LR不仅引起环境问题，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,被认为是肠道肿瘤的理想动物模型。我们通过管饲法给小鼠施用40µg/kgMC-LR，持续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。与对照相比,暴露于MC-LR的小鼠在结肠直肠癌进展中表现出显著的促进,并且在APCmin/+小鼠中表现出肠屏障功能受损。在MC-LR暴露的小鼠中观察到肠道微生物菌群失调，表现出肠道微生物群结构的显著改变。这包括对Marvinbryantia的丰富，Gordonibacter和Family_XIII_AD3011_组以及Faecalibaculum和Lachnoctrdium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）代谢产物增加，特别是牛磺胆酸（TCA），α-胞嘧啶酸（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_组与牛磺胆酸（TCA）呈最强的正相关。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，为饮用水中MC-LR的指导值提供依据。
