Effects of mild moxibustion on intestinal microbiome and NLRP3 inflammasome in rats with 5-fluorouracil-induced intestinal mucositis

作     者：Bing-rong Li Shi-yun Shao Long Yuan Ru Jia Jian Sun Qing Ji Hua Sui Li-hong Zhou Yi Zhang Hui Liu Qi Li Yan Wang Bi-meng Zhang Bing-rong Li;Shi-yun Shao;Long Yuan;Ru Jia;Jian Sun;Qing Ji;Hua Sui;Li-hong Zhou;Yi Zhang;Hui Liu;Qi Li;Yan Wang;Bi-meng Zhang

作者机构：Department of Acupuncture and MoxibustionShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint FunctionFudan UniversityShanghai 200433China Academy of Integrative MedicineShanghai University of Traditional Chinese MedicineDepartment of Medical Oncology&Cancer Institute of Integrative MedicineShuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 201203China 

出 版 物：《Journal of Integrative Medicine》 (结合医学学报（英文版）)

年 卷 期：2021年第19卷第2期

页      面：144-157页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1005[医学-中医学] 1002[医学-临床医学] 100512[医学-针灸推拿学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(No.82030118,82074232,81830120,81774095and 8170388) the Project of Shanghai Science and Technology Committee(No.19401972200) Shanghai Training Project for Leading Talents of Traditional Chinese Medicine(No.ZY[2018-2020]-RCPY-1024)。 

主　　题：Chemotherapy Intestinal mucositis Moxibustion Rats Microbiome NLRP3 

摘      要：Objective:The present study investigated how mild moxibustion treatment affects the intestinal Microbiome and expression of NLRP3-related immune factors in a rat model of intestinal mucositis(IM)induced with 5-fluorouracil(5-Fu).Methods:Forty male Sprague-Dawley rats were randomly divided into control,chemotherapy,moxibustion and probiotics groups.The IM rat model was established by intraperitoneal injection of 5-Fu.Mild moxibustion treatment and intragastric probiotic administration were provided once daily for 15 days.Tissue morphology,serum levels of inflammatory factors and the expression levels of tight junction proteins,caspase-1,gasdermin D and NLRP3 were evaluated in colon tissue,through hematoxylin and eosin staining,electron microscopy,enzyme-linked immunosorbent assay,Western blotting,quantitative realtime reverse transcription polymerase chain reaction and immunofluorescence.Gut microbiome profiling was conducted through 16 S rRNA amplicon sequencing.Results:Moxibustion and probiotic treatments significantly increased the expression levels of tight junction proteins,reduced cell apoptosis and the expression levels of caspase-1,gasdermin D and NLRP3;they also decreased the serum levels of tumor necrosis factor-α,interleukin(IL)-6,IL-1βand IL-18,while increasing serum levels of IL-10.Moxibustion and probiotic treatments also corrected the reduction inα-diversity andβ-diversity in IM rats,greatly increased the proportion of the dominant bacterial genus Lactobacillus and reduced the abundance of the genera Roseburia and Escherichia in chemotherapytreated rats to levels observed in healthy animals.We also found that these dominant genera were firmly correlated with the regulation of pyroptosis-associated proteins and inflammatory factors.Finally,moxibustion and probiotic treatments elicited similar effects in regulating intestinal host-microbial homeostasis and the expression of NLRP3 inflammasome-related factors.Conclusion:Moxibustion exerts its therapeutic effect on IM by ameliorating mucosal damage and reducing inflammation.Moreover,moxibustion modulates the gut microbiota,likely via decreasing the expression levels of the NLRP3 inflammasome.