Volume 22 Issue 1
Jan.  2024
Turn off MathJax
Article Contents
YE Qianqian, LIU Yicheng, LUO Chunsheng, XU Jin, WANG Qingming. Discussion on the mechanism of intestinal flora participating in the pathogenesis of anal fistula by inducing EMT[J]. Chinese Journal of General Practice, 2024, 22(1): 121-125. doi: 10.16766/j.cnki.issn.1674-4152.003346
Citation: YE Qianqian, LIU Yicheng, LUO Chunsheng, XU Jin, WANG Qingming. Discussion on the mechanism of intestinal flora participating in the pathogenesis of anal fistula by inducing EMT[J]. Chinese Journal of General Practice, 2024, 22(1): 121-125. doi: 10.16766/j.cnki.issn.1674-4152.003346

Discussion on the mechanism of intestinal flora participating in the pathogenesis of anal fistula by inducing EMT

doi: 10.16766/j.cnki.issn.1674-4152.003346
Funds:

 SHDC2020CR3094B

 21YF1433300

 23Y11921800

 ZYTSZK1-8

  • Received Date: 2023-07-28
    Available Online: 2024-03-09
  • Anal fistula is a common and frequently-occurring disease in anorectal diseases, with perianal pus, pain, and itching as the main symptoms, and young men as the main patients. At present, the pathogenesis of anal fistula is still unclear, and the main treatment is surgery. The prognosis of surgery is closely related to the surgeon's grasp of the internal opening and the protection of the sphincter. In recent years, the study of intestinal flora has become a hot topic, and its role in various diseases has been gradually confirmed. Studies have shown that changes in the bacterial flora and disturbance of the intestinal microenvironment are involved in the occurrence of anal fistulas, which are specifically manifested in the increase in the abundance and diversity of bacterial flora and the infection of enterogenic bacteria. Epithelial-mesenchymal transition (EMT) is an important phenotypic change in diseases such as cancer. With the deepening of research, it has been proven to be involved in the occurrence and development of anal fistulas, which is especially common in Crohn's disease. Based on the anatomical characteristics and mainstream pathogenesis of anal fistula, this article summarizes the correlation between intestinal flora-EMT-anal fistula by sorting out relevant domestic and foreign researches, from the perspective of intestinal flora and anal fistula, intestinal flora and EMT, and expounds the pathogenesis of anal fistula from three aspects: intestinal flora and anal fistula, intestinal flora and EMT, and EMT and anal fistula. It is concluded that the formation of anal fistula may be due to changes in intestinal flora that affect the homeostasis of the intestinal mucosal barrier, thereby inducing the occurrence of EMT and participating in the development of inflammation-induced fibrosis and fistulas. Since there are few studies on EMT and cryptoglandular anal fistula, this mechanism still needs to be further verified in cryptoglandular anal fistula.This mechanism suggests that in the future, we can participate in the prevention and treatment of anal fistula by regulating the intestinal flora of patients, reducing inflammation and intervening in the process of EMT, in order to provide a new way of non-surgical treatment for anal fistula and reduce the pain of diagnosis and treatment of patients.

     

  • loading
  • [1]
    中国医师协会肛肠医师分会临床指南工作委员会. 肛瘘诊治中国专家共识(2020版)[J]. 中华胃肠外科杂志, 2020, 23(12): 1123-1130. doi: 10.3760/cma.j.cn.441530-20200925-00537

    Clinical Guidelines Working Committee of the Anorectal Physician Branch of the Chinese Medical Doctor Association. Chinese expert consensus on the diagnosis and treatment of anal fistula (2020 edition)[J]. Chinese Journal of Gastroenterology, 2020, 23(12): 1123-1130. doi: 10.3760/cma.j.cn.441530-20200925-00537
    [2]
    程议乐, 武永连, 李万里, 等. 国内肛肠疾病流行病学调查研究进展[J]. 中国肛肠病杂志, 2022, 42(6): 74-76. https://www.cnki.com.cn/Article/CJFDTOTAL-GCBZ202206031.htm

    CHENG Y L, WU Y L, LI W L, et al. Progress in domestic epidemiological investigation of anorectal diseases[J]. Chinese Journal of Coloproctology, 2022, 42(6): 74-76. https://www.cnki.com.cn/Article/CJFDTOTAL-GCBZ202206031.htm
    [3]
    PORTINCASA P, BONFRATE L, VACCA M, et al. Gut microbiota and short chain fatty acids: implications in glucose homeostasis[J]. Int J Mol Sci, 2022, 23(3): 1105. doi: 10.3390/ijms23031105
    [4]
    卢燕, 刘占利. 肠道菌群和癫痫相关性研究进展[J]. 中华全科医学, 2018, 16(9): 1550-1553, 1569. doi: 10.16766/j.cnki.issn.1674-4152.000422

    LU Y, LIU Z L. Research progress on the correlation between intestinal flora and epileps[J]. Chinese Journal of General Practice, 2018, 16(9): 1550-1553, 1569. doi: 10.16766/j.cnki.issn.1674-4152.000422
    [5]
    SETTANNI C R, BIBBÒ S, IANIRO G, et al. Gastrointestinal involvement of autism spectrum disorder: focus on gut microbiota[J]. Expert Rev Gastroenterol Hepatol, 2021, 15(6): 599-622. doi: 10.1080/17474124.2021.1869938
    [6]
    LI Z Z, ZHANG B, WANG N, et al. A novel peptide protects against diet-induced obesity by suppressing appetite and modulating the gut microbiota[J]. Gut, 2023, 72(4): 686-698. doi: 10.1136/gutjnl-2022-328035
    [7]
    MATSON V, CHERVIN C S, GAJEWSKI T F. Cancer and the microbiome-influence of the commensal microbiota on cancer, immune responses, and immunotherapy[J]. Gastroenterology, 2021, 160(2): 600-613. doi: 10.1053/j.gastro.2020.11.041
    [8]
    CHOO J M, MURPHY K J, WADE A T, et al. Interactions between mediterranean diet supplemented with dairy foods and the gut microbiota influence cardiovascular health in an Australian population[J]. Nutrients, 2023, 15(16): 3645. doi: 10.3390/nu15163645
    [9]
    CAPARRÓS E, WIEST R, SCHARL M, et al. Dysbiotic microbiota interactions in Crohn's disease[J]. Gut Microbes, 2021, 13(1): 1949096. DOI: 10.1080/19490976.2021.1949096.
    [10]
    MOLINA-CASTRO S E, TIFFON C, GIRAUD J, et al. The hippo kinase LATS2 controls helicobacter pylori-induced epithelial-mesenchymal transition and intestinal metaplasia in gastric mucosa[J]. Cell Mol Gastroenterol Hepatol, 2020, 9(2): 257-276. doi: 10.1016/j.jcmgh.2019.10.007
    [11]
    RATTO C, LITTA F, LUCCHETTI D, et al. Immunopathological characterization of cryptoglandular anal fistula: a pilot study investigating its pathogenesis[J]. Colorectal Dis, 2016, 18(12): O436-O444. DOI: 10.1111/codi.13527.
    [12]
    赵冬安, 史学文, 朱孟琳. 肛瘘发病机制的研究现状[J]. 中国肛肠病杂志, 2018, 38(2): 73-74. doi: 10.3969/j.issn.1000-1174.2018.02.031

    ZHAO D A, SHI X W, ZHU M L. Research status of the pathogenesis of anal fistula[J]. Chinese Journal of Coloproctology, 2018, 38(2): 73-74. doi: 10.3969/j.issn.1000-1174.2018.02.031
    [13]
    陈伟, 郑雪平. 肛瘘的中西医病因病机(理)研究概况[J]. 中医药临床杂志, 2018, 30(5): 978-981. https://www.cnki.com.cn/Article/CJFDTOTAL-AHLC201805062.htm

    CHEN W, ZHENG X P. Overview of research on the etiology and pathogenesis of anal fistula in traditional Chinese and Western medicine[J]. Clinical Journal of Traditional Chinese Medicine, 2018, 30(5): 978-981. https://www.cnki.com.cn/Article/CJFDTOTAL-AHLC201805062.htm
    [14]
    JAISWAL P, SHARMA S, PRATAP A, et al. Significant presence of biofilm-producing gut-derived bacteria in anal fistula of chronic duration[J]. Int Wound J, 2021, 18(4): 519-524. doi: 10.1111/iwj.13551
    [15]
    LITTA F, PAPAIT A, LUCCHETTI D, et al. The pathogenesis of cryptoglandular anal fistula: new insight into the immunological profile[J]. Colorectal Dis, 2022, 24(12): 1567-1575. doi: 10.1111/codi.16290
    [16]
    SANCHEZ-HARO E, VELA E, CLERIES M, et al. Clinical characterization of patients with anal fistula during follow-up of anorectal abscess: a large population-based study[J]. Tech Coloproctol, 2023, 27(10): 897-907. doi: 10.1007/s10151-023-02840-z
    [17]
    徐飞, 陈燕, 唐迎春, 等. 锌指蛋白521基因多态性对肛周脓肿合并感染患者创面愈合及预后的影响[J]. 中华医院感染学杂志, 2022, 32(19): 2974-2977. https://www.cnki.com.cn/Article/CJFDTOTAL-ZHYY202219020.htm

    XU F, CHEN Y, TANG Y C, et al. Effects of zinc finger protein 521 gene polymorphism on wound healing and prognosis in patients with perianal abscess and infection[J]. Chinese Journal of Nosocomiology, 2022, 32(19): 2974-2977. https://www.cnki.com.cn/Article/CJFDTOTAL-ZHYY202219020.htm
    [18]
    YAMADA S, KANDA Y. Evaluation of barrier functions in human iPSC-derived intestinal epithelium[J]. Methods Mol Biol, 2021, 2367: 27-35.
    [19]
    UNTERSMAYR E, BRANDT A, KOIDL L, et al. The intestinal barrier dysfunction as driving factor of inflammaging[J]. Nutrients, 2022, 14(5): 949. doi: 10.3390/nu14050949
    [20]
    邢肖伟, 陶金华, 江曙, 等. 肠道菌群影响黏膜屏障结构与功能的研究进展[J]. 中国微生态学杂志, 2018, 30(6): 725-730. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGWS201806026.htm

    XING X W, TAO J H, JIANG S, et al. Research progress on the influence of intestinal flora on mucosal barrier structure and function[J]. Chinese Journal of Microbiology, 2018, 30(6): 725-730. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGWS201806026.htm
    [21]
    ROGERS A P, MILETO S J, LYRAS D. Impact of enteric bacterial infections at and beyond the epithelial barrier[J]. Nat Rev Microbiol, 2023, 21(4): 260-274. doi: 10.1038/s41579-022-00794-x
    [22]
    李丹阳, 周瑶, 陶亮. 肠黏膜屏障与病原细菌感染[J]. 生理科学进展, 2022, 53(6): 416-421. doi: 10.3969/j.issn.0559-7765.2022.06.005

    LI D Y, ZHOU Y, TAO L. Intestinal mucosal barrier and pathogenic bacterial infection[J]. Progress in Physiological Sciences, 2022, 53(6): 416-421. doi: 10.3969/j.issn.0559-7765.2022.06.005
    [23]
    王倩, 邹贤军. 克罗恩病肛瘘的外科诊治现状[J]. 临床外科杂志, 2023, 31(6): 521-523. https://www.cnki.com.cn/Article/CJFDTOTAL-LCWK202306006.htm

    WANG Q, ZOU X J. Current status of surgical diagnosis and treatment of anal fistula in Crohn's disease[J]. Journal of Clinical Surgery, 2023, 31(6): 521-523. https://www.cnki.com.cn/Article/CJFDTOTAL-LCWK202306006.htm
    [24]
    CAO S Y, COLONNA M, DEEPAK P. Pathogenesis of perianal fistulising Crohn's disease: current knowledge, gaps in understanding, and future research directions[J]. J Crohns Colitis, 2023, 17(6): 1010-1022. doi: 10.1093/ecco-jcc/jjad008
    [25]
    CHEN Y W, MAI Q D, CHEN Z X, et al. Dietary palmitoleic acid reprograms gut microbiota and improves biological therapy against colitis[J]. Gut Microbes, 2023, 15(1): 2211501. DOI: 10.1080/19490976.2023.2211501.
    [26]
    万仁辉, 翟骁, 鲁瑾, 等. 嗜黏蛋白阿克曼菌与肥胖的关系[J]. 第二军医大学学报, 2019, 40(2): 203-208. https://www.cnki.com.cn/Article/CJFDTOTAL-DEJD201902014.htm

    WAN R H, ZHAI X, LU J, et al. The relationship between Akkermansia muciniphila and obesity[J]. Journal of Second Military Medical University, 2019, 40(2): 203-208. https://www.cnki.com.cn/Article/CJFDTOTAL-DEJD201902014.htm
    [27]
    WADE H, PAN K, DUAN Q H, et al. Akkermansia muciniphila and its membrane protein ameliorates intestinal inflammatory stress and promotes epithelial wound healing via CREBH and miR-143/145[J]. J Biomed Sci, 2023, 30(1): 38. doi: 10.1186/s12929-023-00935-1
    [28]
    杜佳琦, 张卫刚. 探讨肠道菌群与肛瘘的相关性[J]. 上海中医药杂志, 2017, 51(S1): 8-9. https://www.cnki.com.cn/Article/CJFDTOTAL-SHZZ2017S1003.htm

    DU J Q, ZHANG W G. Exploring the correlation between intestinal flora and anal fistula[J]. Shanghai Journal of Traditional Chinese Medicine, 2017, 51(S1): 8-9. https://www.cnki.com.cn/Article/CJFDTOTAL-SHZZ2017S1003.htm
    [29]
    梅婷婷. 肛瘘患者肠道微生物多样性的检测和分析[D]. 杭州: 浙江中医药大学, 2021.

    MEI T T. Detection and analysis of intestinal microbial diversity in patients with anal fistula[D]. Hangzhou: Zhejiang University of Traditional Chinese Medicine, 2021.
    [30]
    裘建明, 杨关根, 王东, 等. 复杂性肛瘘患者肠道微生态检测及分析[J]. 中华胃肠外科杂志, 2022, 25(9): 792-797. doi: 10.3760/cma.j.cn441530-20220412-00142

    QIU J M, YANG G G, WANG D, et al. Detection and analysis of intestinal microecology in patients with complex anal fistula[J]. Chinese Journal of Gastroenterology, 2022, 25(9): 792-797. doi: 10.3760/cma.j.cn441530-20220412-00142
    [31]
    黄进, 褚怡霏, 汪庆明, 等. 基于16S rDNA测序分析湿热下注型肛瘘的局部菌群[J]. 现代医学, 2022, 50(6): 731-735. https://www.cnki.com.cn/Article/CJFDTOTAL-TDYX202206013.htm

    HUANG J, CHU Y F, WANG Q M, et al. Analysis of local bacterial flora of moist-heat injection-type anal fistula based on 16S rDNA sequencing[J]. Modern Medicine, 2022, 50(6): 731-735. https://www.cnki.com.cn/Article/CJFDTOTAL-TDYX202206013.htm
    [32]
    朱静怡, 张玲, 柳奕诚, 等. 黄连解毒汤对湿热下注型肛瘘患者肠道菌群的影响[J]. 上海中医药大学学报, 2022, 36(4): 12-18, 25. https://www.cnki.com.cn/Article/CJFDTOTAL-SHZD202204002.htm

    ZHU J Y, ZHANG L, LIU Y C, et al. Effect of Huanglian Jiedu Decoction on intestinal flora in patients with damp-heat anal fistula[J]. Journal of Shanghai University of Traditional Chinese Medicine, 2022, 36(4): 12-18, 25. https://www.cnki.com.cn/Article/CJFDTOTAL-SHZD202204002.htm
    [33]
    刘道成, 陈金明, 杨关根, 等. Vimentin表达水平与肛瘘感染细菌谱以及患者临床特征的关系研究[J]. 结直肠肛门外科, 2019, 25(1): 43-47. https://www.cnki.com.cn/Article/CJFDTOTAL-DCGM201901013.htm

    LIU D C, CHEN J M, YANG G G, et al. Study on the relationship between vimentin expression level, bacterial spectrum of anal fistula infection and clinical characteristics of patients[J]. Colorectal and anal surgery, 2019, 25(1): 43-47. https://www.cnki.com.cn/Article/CJFDTOTAL-DCGM201901013.htm
    [34]
    CAI P, RONG H, ZHU Q Q, et al. The potential roles of gut microbiome in anal fistula[J]. AMB Express, 2023, 13(1): 58. doi: 10.1186/s13568-023-01560-9
    [35]
    WŁODARCZYK M, WŁODARCZYK J, SOBOLEWSKA-WŁODAR CZYK A, et al. Current concepts in the pathogenesis of cryptoglandular perianal fistula[J]. J Int Med Res, 2021, 49(2): 30006052098 6669. DOI: 10.1177/0300060520986669.
    [36]
    SUGRUE J, NORDENSTAM J, ABCARIAN H, et al. Pathogenesis and persistence of cryptoglandular anal fistula: a systematic review[J]. Tech Coloproctol, 2017, 21(6): 425-432.
    [37]
    JAISWAL P, SHARMA S, PRATAP A, et al. Significant presence of biofilm-producing gut-derived bacteria in anal fistula of chronic duration[J]. Int Wound J, 2021, 18(4): 519-524.
    [38]
    WAN G S, XIE M L, YU H J, et al. Intestinal dysbacteriosis activates tumor-associated macrophages to promote epithelial-mesenchymal transition of colorectal cancer[J]. Innate Immun, 2018, 24(8): 480-489.
    [39]
    XU S Y, LIU Z Z, LV M H, et al. Intestinal dysbiosis promotes epithelial-mesenchymal transition by activating tumor-associated macrophages in ovarian cancer[J]. Pathog Dis, 2019, 77(2): ftz019. DOI: 10.1093/femspd/ftz019.
    [40]
    CHANDRAKESAN P, ROY B, JAKKULA L U, et al. Utility of a bacterial infection model to study epithelial-mesenchymal transition, mesenchymal-epithelial transition or tumorigenesis[J]. Oncogene, 2014, 33(20): 2639-2654.
    [41]
    SONG X L, AN Y P, CHEN D F, et al. Microbial metabolite deoxycholic acid promotes vasculogenic mimicry formation in intestinal carcinogenesis[J]. Cancer Sci, 2022, 113(2): 459-477.
    [42]
    WARYAH C, CURSONS J, FOROUTAN M, et al. Synthetic epigenetic reprogramming of mesenchymal to epithelial states using the CRISPR/dCas9 platform in triple negative breast cancer[J]. Adv Sci (Weinh), 2023, 10(22): e2301802. DOI: 10.1002/advs.202301802.
    [43]
    DONGRE A, WEINBERG R A. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer[J]. Nat Rev Mol Cell Biol, 2019, 20(2): 69-84.
    [44]
    ZHANG N, NG A S, CAI S J, et al. Novel therapeutic strategies: targeting epithelial-mesenchymal transition in colorectal cancer[J]. Lancet Oncol, 2021, 22(8): e358-e368.
    [45]
    JAYACHANDRAN J, SRINIVASAN H, MANI K P. Molecular mechanism involved in epithelial to mesenchymal transition[J]. Arch Biochem Biophys, 2021, 710: 108984. DOI: 10.1016/j.abb.2021.108984.
    [46]
    MCGREGOR C G C, TANDON R, SIMMONS A. Pathogenesis of fistulating Crohn's disease: a review[J]. Cell Mol Gastroenterol Hepatol, 2023, 15(1): 1-11.
    [47]
    OSMAN N H, JAILANI R F, RAHMAN H A, et al. Gene and protein expression of epithelial to mesenchymal transition for intestinal and anal fistula: a systematic review[J]. Ann Coloproctol, 2023, 39(2): 106-114.
    [48]
    BRUCKNER R S, SPALINGER M R, BARNHOORN M C, et al. Contribution of CD3+CD8- and CD3+CD8+ T cells to TNF-α overexpression in Crohn disease-associated perianal fistulas and induction of epithelial-mesenchymal transition in HT-29 cells[J]. Inflamm Bowel Dis, 2021, 27(4): 538-549.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(1)  / Tables(2)

    Article Metrics

    Article views (155) PDF downloads(12) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return