Wang Jui-Ling, Chen Yu-Siang, Huang Kuo-Chin, Yeh Chin-Hsing, Chen Miles Chih-Ming, Wu Lawrence Shih-Hsin, Chiu Yi-Han
Animal Testing Division, National Laboratory Animal Center, National Applied Research Laboratories, Tainan 744, Taiwan.
Department of Microbiology, Soochow University, Taipei 111, Taiwan.
Biomedicines. 2024 Jun 28;12(7):1450. doi: 10.3390/biomedicines12071450.
5-Fluorouracil (5-FU) is commonly used as the primary chemotherapy for colorectal cancer (CRC). However, it can lead to unwanted chemoresistance. Resistant starch (RS), which functions similarly to fermentable dietary fiber, has the potential to reduce the risk of CRC. The effects of RS on improving CRC-associated cachectic symptoms and 5-FU chemotherapy-induced microbial dysbiosis remain unknown. Female BALB/cByJNarl mice were randomly divided into four groups: one tumor group (with CT26 colonic carcinoma but no treatment) and three CT26 colonic carcinoma-bearing groups that were administered 20 mg/kg 5-FU (T+5-FU group), a probiotic cocktail (4 × 10 CFUs) plus chemotherapy (T+5-FU+Pro), or resistant-starch-encapsulated probiotics plus chemotherapy (T+5-FU+RS-Pro). T+5-FU and T+5-FU+RS-Pro administration significantly suppressed tumor growth and activated apoptotic cell death in CT26-bearing mice. 5-FU-induced increases in inflammatory cytokines and NF-κB signaling were mitigated by the Pro or RS-Pro supplementation. A gut microbial composition comparison indicated that the abundance of intestinal bacteria in the T and T+5-FU groups decreased significantly, while the groups receiving Pro or RS-Pro maintained a greater abundance and healthy gut microbiota composition, suggesting that RS can reduce the microbial dysbiosis that occurs during 5-FU chemotherapy. The use of RS-Pro before chemotherapy should be considered for the regulation of chemotherapy-associated cachectic symptoms, inflammation, and chemotherapy-induced microbial dysbiosis.
5-氟尿嘧啶（5-FU）是结直肠癌（CRC）常用的一线化疗药物。然而，它可能会导致不良的化疗耐药性。抗性淀粉（RS）的功能与可发酵膳食纤维相似，有可能降低患CRC的风险。RS对改善CRC相关恶病质症状和5-FU化疗诱导的微生物群落失调的影响尚不清楚。将雌性BALB/cByJNarl小鼠随机分为四组：一组肿瘤组（患有CT26结肠癌但未接受治疗）和三组携带CT26结肠癌的组，分别给予20mg/kg 5-FU（T+5-FU组）、益生菌混合物（4×10CFUs）加化疗（T+5-FU+Pro）或抗性淀粉包封的益生菌加化疗（T+5-FU+RS-Pro）。给予T+5-FU和T+5-FU+RS-Pro可显著抑制携带CT26的小鼠的肿瘤生长并激活凋亡性细胞死亡。补充Pro或RS-Pro可减轻5-FU诱导的炎性细胞因子增加和NF-κB信号传导。肠道微生物组成比较表明，T组和T+5-FU组的肠道细菌丰度显著降低，而接受Pro或RS-Pro的组保持了更高的丰度和健康的肠道微生物群组成，这表明RS可以减少5-FU化疗期间发生的微生物群落失调。化疗前使用RS-Pro应被视为调节化疗相关恶病质症状、炎症和化疗诱导的微生物群落失调的方法。
