Alteration of Gut Microbiota and Inflammatory Cytokine/Chemokine Profiles in 5-Fluorouracil Induced Intestinal Mucositis.
Alteration of Gut Microbiota and Inflammatory Cytokine/Chemokine Profiles in 5-Fluorouracil Induced Intestinal Mucositis.
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DOI：
10.3389/fcimb.2017.00455
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发表时间：
2017
影响因子：
5.7
通讯作者：
Wu XJ
中科院分区：
文献类型：
--
作者：
Li HL;Lu L;Wang XS;Qin LY;Wang P;Qiu SP;Wu H;Huang F;Zhang BB;Shi HL;Wu XJ
肠道微生物群的稳态失调与5-氟尿嘧啶（5-Fu）诱导的粘膜炎密切相关。然而，目前对5-Fu干扰的肠道微生物群的总体概况的了解是有限的，到目前为止，还没有直接令人信服的证据证明5-Fu干扰的微生物群和结肠粘膜炎之间的因果关系。在小鼠中，与以前的报道一致，5-Fu导致严重的结肠粘膜炎，表现为体重减轻、腹泻、血便、结肠缩短和炎性细胞浸润。它显著改变了血清和结肠中炎性细胞因子/趋化因子的谱。粘附分子如血管细胞粘附分子-1（VCAM-1）、细胞间粘附分子-1（ICAM-1）和VE-钙粘蛋白增加。5-Fu处理组小鼠结肠组织紧密连接蛋白occludin表达减少，而紧密连接蛋白ZO-1和连接粘附分子A表达增加。同时，炎症相关信号通路NF-κB和丝裂原活化蛋白激酶（MAPK）也被激活。进一步的研究发现，5-Fu降低了肠道细菌群落的丰富度和多样性，导致粪便和盲肠内容物中厚壁菌门的丰度相对较低，厚壁菌门/拟杆菌门（F/B）比值降低。5-Fu还降低了粪便和/或盲肠内容物中变形菌门、Tenericutes门、蓝细菌门和候选菌门TM 7的比例，但增加了疣微菌门和放线菌门的比例。从健康小鼠的粪便移植防止体重减轻和结肠缩短的5-Fu治疗的小鼠。此外，5-Fu处理小鼠的粪便移植减少了万古霉素预处理小鼠的体重和结肠长度。总之，我们的研究表明，肠道微生物群积极参与了5-Fu诱导的肠粘膜炎的病理过程，表明通过操纵肠道微生物群稳态可能减轻5-Fu诱导的肠粘膜炎。
Disturbed homeostasis of gut microbiota has been suggested to be closely associated with 5-fluorouracil (5-Fu) induced mucositis. However, current knowledge of the overall profiles of 5-Fu-disturbed gut microbiota is limited, and so far there is no direct convincing evidence proving the causality between 5-Fu-disturbed microbiota and colonic mucositis. In mice, in agreement with previous reports, 5-Fu resulted in severe colonic mucositis indicated by weight loss, diarrhea, bloody stool, shortened colon, and infiltration of inflammatory cells. It significantly changed the profiles of inflammatory cytokines/chemokines in serum and colon. Adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and VE-Cadherin were increased. While tight junction protein occludin was reduced, however, zonula occludens-1 (ZO-1) and junctional adhesion molecule-A (JAM-A) were increased in colonic tissues of 5-Fu treated mice. Meanwhile, inflammation related signaling pathways including NF-κB and mitogen activated protein kinase (MAPKs) in the colon were activated. Further study disclosed that 5-Fu diminished bacterial community richness and diversity, leading to the relative lower abundance of Firmicutes and decreased Firmicutes/Bacteroidetes (F/B) ratio in feces and cecum contents. 5-Fu also reduced the proportion of Proteobacteria, Tenericutes, Cyanobacteria, and Candidate division TM7, but increased that of Verrucomicrobia and Actinobacteria in feces and/or cecum contents. The fecal transplant from healthy mice prevented body weight loss and colon shortening of 5-Fu treated mice. In addition, the fecal transplant from 5-Fu treated mice reduced body weight and colon length of vancomycin-pretreated mice. Taken together, our study demonstrated that gut microbiota was actively involved in the pathological process of 5-Fu induced intestinal mucositis, suggesting potential attenuation of 5-Fu induced intestinal mucositis by manipulating gut microbiota homeostasis.
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DOI：
10.1590/1414-431x20144360
发表时间：
2015-06
期刊：
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
影响因子：
--
作者：
Araújo CV;Lazzarotto CR;Aquino CC;Figueiredo IL;Costa TB;Alves LA;Ribeiro RA;Bertolini LR;Lima AA;Brito GA;Oriá RB
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Oriá RB
影响因子：
4.6
作者：
Hui W;Zhao C;Bourgoin SG
通讯作者：
Bourgoin SG
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影响因子：
3.6
作者：
Gao, Jing;Gao, Jin;Han, Wei
通讯作者：
Han, Wei
DOI：
10.1016/j.bbrc.2017.01.058
发表时间：
2017-04-01
影响因子：
3.1
作者：
Kim, Mi-Kyoung;Park, Hyun-Joo;Bae, Moon-Kyoung
通讯作者：
Bae, Moon-Kyoung
影响因子：
3.7
作者：
Chang, Chung-Ta;Ho, Tin-Yun;Hsiang, Chien-Yun
通讯作者：
Hsiang, Chien-Yun