Probiotic Bifidobacterium bifidum G9-1 attenuates 5-fluorouracil-induced intestinal mucositis in mice via suppression of dysbiosis-related secondary inflammatory responses
Probiotic Bifidobacterium bifidum G9-1 attenuates 5-fluorouracil-induced intestinal mucositis in mice via suppression of dysbiosis-related secondary inflammatory responses
复制标题
DOI：
10.1111/1440-1681.12792
复制
发表时间：
2017-10-01
影响因子：
2.9
通讯作者：
Shimakawa, Masaki
中科院分区：
文献类型：
--
作者：
Kato, Shinichi;Hamouda, Nahla;Shimakawa, Masaki
双歧杆菌是肠道微生物群的主要成分，临床上已用于治疗腹泻和便秘。5-氟尿嘧啶（5-FU），广泛用于癌症化疗，是众所周知的，经常诱发肠粘膜炎伴随着严重的腹泻。本研究探讨了两歧双歧杆菌G9-1（BBG 9 -1）对5-FU诱导的小鼠肠粘膜炎的影响。采用5-FU重复给药6天的方法，诱发大鼠肠粘膜炎。在5-FU治疗开始前3d开始口服BBG 9 -1，每日一次，共9d。5-FU重复给药引起严重的肠粘膜炎，其特征为绒毛缩短和隐窝破坏，伴有肠髓过氧化物酶活性和炎性细胞因子表达增加，体重减轻和第6天腹泻。每日施用BBG 9 -1显著降低了肠粘膜炎和炎症反应的严重程度，并且倾向于减轻临床症状。相反，BBG 9 -1在第一次5-FU给药后第1天未能阻止凋亡诱导。如通过加权UniFrac距离分析的，肠道微生物群的结构在很大程度上被5-FU治疗改变，但这种变化通过每日施用BBG 9 -1而减轻。此外，5-FU处理降低了厚壁菌门的丰度并增加了拟杆菌门的丰度，但这些反应也被每日施用BBG 9 -1显著抑制。这些结果表明，BBG 9 -1通过改善微生态失调来减轻炎症反应，从而对5-FU诱导的肠粘膜炎具有改善作用。BBG 9 -1可能对预防癌症化疗期间的肠粘膜炎有用。
Bifidobacterium, a major component of the intestinal microbiota, has been clinically used for the treatment of diarrhoea and constipation. 5-Fluorouracil (5-FU), widely used for cancer chemotherapy, is known to frequently induce intestinal mucositis accompanied by severe diarrhoea. The present study examined the effect of Bifidobacterium bifidum G9-1 (BBG9-1) on 5-FU-induced intestinal mucositis in mice. Intestinal mucositis was induced by repeated administration of 5-FU for 6days. BBG9-1 was administered orally once daily for 9days, beginning 3days before the onset of 5-FU treatment. Repeated administration of 5-FU caused severe intestinal mucositis, characterised by shortening of villi and destruction of crypts, accompanied by increases in intestinal myeloperoxidase activity and inflammatory cytokine expression, body weight loss, and diarrhoea on day 6. Daily administration of BBG9-1 significantly reduced the severity of intestinal mucositis and inflammatory responses and tended to attenuate clinical symptoms. In contrast, BBG9-1 failed to prevent apoptosis induction on day 1 after the first 5-FU administration. The structure of the intestinal microbiota, as analysed by weighted UniFrac distance, was largely altered by 5-FU treatment, but this change was mitigated by daily administration of BBG9-1. Moreover, 5-FU treatment decreased the abundance of Firmicutes and increased the abundance of Bacteroidetes, but these responses were also significantly inhibited by daily administration of BBG9-1. These results suggest that BBG9-1 has an ameliorative effect against 5-FU-induced intestinal mucositis through the attenuation of inflammatory responses via improve dysbiosis. BBG9-1 could be useful for the prevention of intestinal mucositis during cancer chemotherapy.