Alteration of Gut Microbiota and Inflammatory Cytokine/Chemokine Profiles in 5-Fluorouracil Induced Intestinal Mucositis
| Autor: | Ping Wang, Fei Huang, Hailian Shi, Xiaojun Wu, Hong-Li Li, Liyue Qin, Xiao-Shuang Wang, Lan Lu, Hui Wu, Shui-Ping Qiu, Beibei Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Chemokine lcsh:QR1-502 Gut flora Occludin lcsh:Microbiology Cecum Feces Mice 0302 clinical medicine Intestinal mucosa RNA Ribosomal 16S 5-fluorouracil Intestinal Mucosa Original Research Mice Inbred BALB C NF-kappa B Fecal Microbiota Transplantation intestinal mucositis Cadherins Intercellular Adhesion Molecule-1 Immunohistochemistry Intestines medicine.anatomical_structure Infectious Diseases 030220 oncology & carcinogenesis Cytokines Fluorouracil Chemokines Mitogen-Activated Protein Kinases Microbiology (medical) Mucositis inflammatory chemokines/cytokines Colon Immunology Vascular Cell Adhesion Molecule-1 Receptors Cell Surface Biology Microbiology Proinflammatory cytokine 03 medical and health sciences Antigens CD medicine Animals fecal transplantation Inflammation gut microbiota Bacteria Body Weight medicine.disease biology.organism_classification Gastrointestinal Microbiome 030104 developmental biology biology.protein Zonula Occludens-1 Protein Cell Adhesion Molecules |
| Zdroj: | Frontiers in Cellular and Infection Microbiology Frontiers in Cellular and Infection Microbiology, Vol 7 (2017) |
| ISSN: | 2235-2988 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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