口服紫杉醇酵母细胞通过调控肠道菌群增强 抗肿瘤疗效

Oral Paclitaxel-Loaded Yeast Cells Enhance Antitumor Effects via Modulating Gut Microbiota

摘要: 紫杉醇(Paclitaxel, PTX)作为结直肠癌临床一线化疗药物，在发挥抗肿瘤作用的同时，常伴随肠黏膜损伤与肠道微生态失衡，导致口服给药的安全性与应用效果均受到明显制约。本研究构建酵母菌细胞壁载紫杉醇微粒(YPs-PTX)，系统考察其体内抑瘤效应与肠道菌群的调控效应。结果显示，YPs-PTX可有效抑制原位结直肠癌生长，降低肿瘤负荷并保护肠道结构完整性。16S rRNA高通量测序表明，YPs-PTX可显著逆转肿瘤及化疗诱导的肠道菌群紊乱，恢复菌群的α与β多样性，提高Lactobacillus、Akkermansia等有益菌丰度，降低Escherichia-Shigella等致病菌增殖。综上，YPs-PTX可通过改善肠道药物递送效率与重塑肠道微环境发挥协同增效作用，在强化抗肿瘤效果的同时减轻化疗相关肠道损伤，为口服紫杉醇治疗结直肠癌提供安全高效的新思路。

Abstract: Paclitaxel (PTX), a first-line chemotherapeutic agent for colorectal cancer, is often accompanied by intestinal mucosal injury and intestinal microecological imbalance during antitumor therapy, which significantly restricts the safety and efficacy of its oral administration. In this study, yeast cell wall-encapsulated paclitaxel microparticles (YPs-PTX) were constructed, and their in vivo antitumor efficacy and regulatory effect on intestinal microbiota were systematically investigated. The results demonstrated that YPs-PTX effectively inhibited the growth of orthotopic colorectal cancer, reduced tumor burden, and protected intestinal structural integrity. 16S rRNA high-throughput sequencing revealed that YPs-PTX significantly reversed tumor- and chemotherapy-induced intestinal microbiota dysbiosis, restored microbiota α- and β-diversity, increased the abundance of beneficial bacteria such as Lactobacillus and Akkermansia, and inhibited the proliferation of pathogenic bacteria including Escherichia-Shigella. In conclusion, YPs-PTX can exert a synergistic effect by improving intestinal drug delivery efficiency and regulating the intestinal microenvironment, enhancing antitumor efficacy while alleviating chemotherapy-related intestinal damage, providing a safe and efficient novel strategy for oral paclitaxel in the treatment of colorectal cancer.