Methotrexate (MTX) is a widely used therapeutic agent for the treatment of cancer and autoimmune diseases. However, its efficacy is often limited by adverse effects, such as intestinal toxicity. Although treatment with leucovorin (LV) is the most common method to reduce the toxic effects of MTX, it may also compromise the therapeutic effects of MTX. The gut microbiome has been reported to be associated with the intestinal toxicity of MTX. In this study, the intestinal damage of MTX was ameliorated by treatment with LV. Moreover, the population, diversity, and principal components of the gut microbiota in MTX-treated mice were restored by treatment with LV. The only element of the gut microbiota that was significantly changed after treatment with LV was Bifidobacterium, and supplementation with Bifidobacterium longum ameliorated MTX-induced intestinal damage. In conclusion, our results suggest that the balance and the composition of gut microbiota have an important role in the LV-mediated protection against MTX-induced intestinal toxicity. This work provides foundation of data in support of a new potential mechanism for the prevention of MTX-induced intestinal toxicity.

中文翻译：

---

白蛋白通过调节肠道菌群改善了甲氨蝶呤引起的肠毒性。

甲氨蝶呤（MTX）是广泛用于治疗癌症和自身免疫性疾病的治疗剂。但是，其功效通常受到诸如肠道毒性等不良影响的限制。尽管用亚叶酸（LV）进行治疗是降低MTX毒性作用的最常见方法，但它也可能会损害MTX的治疗作用。据报道肠道微生物组与MTX的肠道毒性有关。在这项研究中，LV治疗可以改善MTX的肠道损伤。此外，MTX处理小鼠的肠道菌群的种群，多样性和主要组成部分通过LV处理得以恢复。LV处理后，肠道菌群中唯一发生显着变化的元素是双歧杆菌，补充长双歧杆菌可改善MTX引起的肠道损伤。总之，我们的结果表明，肠道菌群的平衡和组成在LV介导的针对MTX诱导的肠道毒性的保护中具有重要作用。这项工作提供了数据基础，以支持预防MTX诱导的肠毒性的新的潜在机制。