Research Advances in the Treatment of Inflammation Bowel Disease Using Escherichia coli Nissle 1917

doi:10.13560/j.cnki.biotech.bull.1985.2022-1027

Abstract

Abstract:

Inflammatory bowel disease（IBD）is a general term of a group of specific intestinal diseases, mainly manifested as chronic and recurrent intestinal inflammation. The burden of IBD has been a global health concern since its incidence and prevalence are elevating rapidly, which has seriously affected people's life and health quality. Over the past decades, tremendous studies underlined the association between incidence of IBD with imbalance of intestinal flora. Therefore, the treatment strategy based on probiotics has become the focus, among of them Escherichia coli Nissle 1917（EcN）has received accumulative attentions. In the current work, we focused on the application and mechanisms of EcN in the treatment of IBD, systematically reviewed the probiotic properties of EcN and its application for treating IBD through regulating epithelial integrity, immune-modulation, mucus protection and gut microbiota homeostasis. Furthermore, the future perspectives on formulating novel therapies based on engineered EcN were discussed, highlighting the applicable and feasible strategies of EcN in IBD curing and prevention. Besides, the prospects for further research in this field were given, providing ideas and references for further in-depth research on the EcN treatment of IBD.

Key words: inflammatory bowel disease, Escherichia coli Nissle 1917, therapeutic effect

CHEN Cai-ping, REN Hao, LONG Teng-fei, HE Bing, LU Zhao-xiang, SUN Jian. Research Advances in the Treatment of Inflammation Bowel Disease Using Escherichia coli Nissle 1917[J]. Biotechnology Bulletin, 2023, 39(6): 109-118.

Figures/Tables 2

References 69

[1]	Aggeletopoulou I, Konstantakis C, Assimakopoulos SF, et al. The role of the gut microbiota in the treatment of inflammatory bowel diseases[J]. Microb Pathog, 2019, 137: 103774. doi: 10.1016/j.micpath.2019.103774 URL
[2]	Stange EF, Schroeder BO. Microbiota and mucosal defense in IBD: an update[J]. Expert Rev Gastroenterol Hepatol, 2019, 13(10): 963-976. doi: 10.1080/17474124.2019.1671822 URL
[3]	Wassenaar TM. Insights from 100 years of research with probiotic E. coli[J]. Eur J Microbiol Immunol(Bp), 2016, 6(3): 147-161.
[4]	Grozdanov L, Raasch C, Schulze J, et al. Analysis of the genome structure of the nonpathogenic probiotic Escherichia coli strain Nissle 1917[J]. J Bacteriol, 2004, 186(16): 5432-5441. doi: 10.1128/JB.186.16.5432-5441.2004 pmid: 15292145
[5]	Nougayrède JP, Chagneau CV, Motta JP, et al. A toxic friend: genotoxic and mutagenic activity of the probiotic strain Escherichia coli nissle 1917[J]. mSphere, 2021, 6(4): e0062421. doi: 10.1128/mSphere.00624-21 URL
[6]	Monteiro C, Saxena I, Wang XD, et al. Characterization of cellulose production in Escherichia coli Nissle 1917 and its biological consequences[J]. Environ Microbiol, 2009, 11(5): 1105-1116. doi: 10.1111/j.1462-2920.2008.01840.x pmid: 19175667
[7]	Zhao ZJ, Xu SM, Zhang WY, et al. Probiotic Escherichia coli Nissle 1917 for inflammatory bowel disease applications[J]. Food Funct, 2022, 13(11): 5914-5924. doi: 10.1039/D2FO00226D URL
[8]	Lasaro MA, Salinger N, Zhang J, et al. F1C fimbriae play an important role in biofilm formation and intestinal colonization by the Escherichia coli commensal strain Nissle 1917[J]. Appl Environ Microbiol, 2009, 75(1): 246-251. doi: 10.1128/AEM.01144-08 URL
[9]	Kleta S, Nordhoff M, Tedin K, et al. Role of F1C fimbriae, flagella, and secreted bacterial components in the inhibitory effect of probiotic Escherichia coli Nissle 1917 on atypical enteropathogenic E. coli infection[J]. Infect Immun, 2014, 82(5): 1801-1812. doi: 10.1128/IAI.01431-13 URL
[10]	Behnsen J, Deriu E, Sassone-Corsi M, et al. Probiotics: properties, examples, and specific applications[J]. Cold Spring Harb Perspect Med, 2013, 3(3): a010074.
[11]	Deriu E, Liu JZ, Pezeshki M, et al. Probiotic bacteria reduce Salmonella typhimurium intestinal colonization by competing for iron[J]. Cell Host Microbe, 2013, 14(1): 26-37. doi: 10.1016/j.chom.2013.06.007 URL
[12]	Schlee M, Wehkamp J, Altenhoefer A, et al. Induction of human beta-defensin 2 by the probiotic Escherichia coli Nissle 1917 is mediated through flagellin[J]. Infect Immun, 2007, 75(5): 2399-2407. doi: 10.1128/IAI.01563-06 URL
[13]	Sassone-Corsi M, Nuccio SP, Liu H, et al. Microcins mediate competition among Enterobacteriaceae in the inflamed gut[J]. Nature, 2016, 540(7632): 280-283. doi: 10.1038/nature20557
[14]	Möndel M, Schroeder BO, Zimmermann K, et al. Probiotic E. coli treatment mediates antimicrobial human beta-defensin synthesis and fecal excretion in humans[J]. Mucosal Immunol, 2009, 2(2): 166-172. doi: 10.1038/mi.2008.77 pmid: 19129752
[15]	Langan RC, Gotsch PB, Krafczyk MA, et al. Ulcerative colitis: diagnosis and treatment[J]. Am Fam Physician, 2007, 76(9): 1323-1330. pmid: 18019875
[16]	Fumery M, Singh S, Dulai PS, et al. Natural history of adult ulcerative colitis in population-based cohorts: a systematic review[J]. Clin Gastroenterol Hepatol, 2018, 16(3): 343-356.e3. doi: 10.1016/j.cgh.2017.06.016 URL
[17]	Bruscoli S, Febo M, Riccardi C, et al. Glucocorticoid therapy in inflammatory bowel disease: mechanisms and clinical practice[J]. Front Immunol, 2021, 12: 691480. doi: 10.3389/fimmu.2021.691480 URL
[18]	Yang VW. Eicosanoids and inflammatory bowel disease[J]. Gastroenterol Clin North Am, 1996, 25(2): 317-332. doi: 10.1016/S0889-8553(05)70249-1 URL
[19]	张国兴, 石荣. 溃疡性结肠炎治疗进展[J]. 现代中西医结合杂志, 2019, 28(25): 2842-2847.
	Zhang GX, Shi R. Progerss in the treatment of ulcerative colitis[J]. Mod J Integr Tradit Chin West Med, 2019, 28(25): 2842-2847.
[20]	Ko JK, Auyeung KK. Inflammatory bowel disease: etiology, pathogenesis and current therapy[J]. Curr Pharm Des, 2014, 20(7): 1082-1096. doi: 10.2174/13816128113199990416 URL
[21]	Loftus EV Jr, Kane SV, Bjorkman D. Systematic review: short-term adverse effects of 5-aminosalicylic acid agents in the treatment of ulcerative colitis[J]. Aliment Pharmacol Ther, 2004, 19(2): 179-189. doi: 10.1111/apt.2004.19.issue-2 URL
[22]	Rogler G. Gastrointestinal and liver adverse effects of drugs used for treating IBD[J]. Best Pract Res Clin Gastroenterol, 2010, 24(2): 157-165. doi: 10.1016/j.bpg.2009.10.011 pmid: 20227029
[23]	Sha S, Xu B, Kong X, et al. Preventive effects of Escherichia coli strain Nissle 1917 with different courses and different doses on intestinal inflammation in murine model of colitis[J]. Inflamm Res, 2014, 63(10): 873-883. doi: 10.1007/s00011-014-0761-1 URL
[24]	Dembiñski A, Warzecha Z, Ceranowicz P, et al. Synergic interaction of rifaximin and mutaflor(Escherichia coli Nissle 1917)in the treatment of acetic acid-induced colitis in rats[J]. Gastroenterol Res Pract, 2016, 2016: 3126280.
[25]	Garrido-Mesa N, Utrilla P, Comalada M, et al. The association of minocycline and the probiotic Escherichia coli Nissle 1917 results in an additive beneficial effect in a DSS model of reactivated colitis in mice[J]. Biochem Pharmacol, 2011, 82(12): 1891-1900. doi: 10.1016/j.bcp.2011.09.004 pmid: 21930116
[26]	Souza ÉL, Elian SD, Paula LM, et al. Escherichia coli strain Nissle 1917 ameliorates experimental colitis by modulating intestinal permeability, the inflammatory response and clinical signs in a faecal transplantation model[J]. J Med Microbiol, 2016, 65(3): 201-210. doi: 10.1099/jmm.0.000222 URL
[27]	Kruis W, Schütz E, Fric P, et al. Double-blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis[J]. Aliment Pharmacol Ther, 1997, 11(5): 853-858. doi: 10.1046/j.1365-2036.1997.00225.x URL
[28]	Rembacken BJ, Snelling AM, Hawkey PM, et al. Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial[J]. Lancet, 1999, 354(9179): 635-639. doi: 10.1016/s0140-6736(98)06343-0 pmid: 10466665
[29]	Kruis W, Fric P, Pokrotnieks J, et al. Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine[J]. Gut, 2004, 53(11): 1617-1623. doi: 10.1136/gut.2003.037747 pmid: 15479682
[30]	Henker J, Müller S, Laass MW, et al. Probiotic Escherichia coli Nissle 1917(EcN)for successful remission maintenance of ulcerative colitis in children and adolescents: an open-label pilot study[J]. Z Gastroenterol, 2008, 46(9): 874-875. doi: 10.1055/s-2008-1027463 pmid: 18810672
[31]	Malchow HA. Crohn's disease and Escherichia coli. A new approach in therapy to maintain remission of colonic Crohn's disease?[J]. J Clin Gastroenterol, 1997, 25(4): 653-658. doi: 10.1097/00004836-199712000-00021 pmid: 9451682
[32]	Campbell HK, Maiers JL, DeMali KA. Interplay between tight junctions & adherens junctions[J]. Exp Cell Res, 2017, 358(1): 39-44. doi: S0014-4827(17)30187-8 pmid: 28372972
[33]	González-Mariscal L, Quirós M, Díaz-Coránguez M. ZO proteins and redox-dependent processes[J]. Antioxid Redox Signal, 2011, 15(5): 1235-1253. doi: 10.1089/ars.2011.3913 URL
[34]	Ukena SN, Singh A, Dringenberg U, et al. Probiotic Escherichia coli Nissle 1917 inhibits leaky gut by enhancing mucosal integrity[J]. PLoS One, 2007, 2(12): e1308. doi: 10.1371/journal.pone.0001308 pmid: 18074031
[35]	Alvarez CS, Badia J, Bosch M, et al. Outer membrane vesicles and soluble factors released by probiotic Escherichia coli Nissle 1917 and commensal ECOR63 enhance barrier function by regulating expression of tight junction proteins in intestinal epithelial cells[J]. Front Microbiol, 2016, 7: 1981.
[36]	Veltman K, Hummel S, Cichon C, et al. Identification of specific miRNAs targeting proteins of the apical junctional complex that simulate the probiotic effect of E. coli Nissle 1917 on T84 epithelial cells[J]. Int J Biochem Cell Biol, 2012, 44(2): 341-349. doi: 10.1016/j.biocel.2011.11.006 URL
[37]	Zyrek AA, Cichon C, Helms S, et al. Molecular mechanisms underlying the probiotic effects of Escherichia coli Nissle 1917 involve ZO-2 and PKCξ redistribution resulting in tight junction and epithelial barrier repair[J]. Cell Microbiol, 2007, 9(3): 804-816. doi: 10.1111/cmi.2007.9.issue-3 URL
[38]	Krause G, Winkler L, Mueller SL, et al. Structure and function of claudins[J]. Biochim Biophys Acta, 2008, 1778(3): 631-645. doi: 10.1016/j.bbamem.2007.10.018 pmid: 18036336
[39]	冯燕海, 王凤君. 紧密连接蛋白Claudin-2研究进展[J]. 重庆医学, 2018, 47(5): 697-699.
	Feng YH, Wang FJ. Progerss of tight junction associated protein Claudin-2[J]. Chongqing Med, 2018, 47(5): 697-699.
[40]	Hering NA, Richter JF, Fromm A, et al. TcpC protein from E. coli Nissle improves epithelial barrier function involving PKCζ and ERK1/2 signaling in HT-29/B6 cells[J]. Mucosal Immunol, 2014, 7(2): 369-378. doi: 10.1038/mi.2013.55 pmid: 23900194
[41]	Wang YR, et al. The administration of Escherichia coli Nissle 1917 ameliorates irinotecan-induced intestinal barrier dysfunction and gut microbial dysbiosis in mice[J]. Life Sci, 2019, 231: 116529. doi: 10.1016/j.lfs.2019.06.004 URL
[42]	Feldman GJ, Mullin JM, Ryan MP. Occludin: structure, function and regulation[J]. Adv Drug Deliv Rev, 2005, 57(6): 883-917. doi: 10.1016/j.addr.2005.01.009 URL
[43]	徐妹燕, 富建华. 紧密连接相关蛋白Occludin的研究进展[J]. 国际儿科学杂志, 2012(5):451-454.
	Xu MY, Fu JH. Progress of tight junction associated protein occludin[J]. Int J Pediatr, 2012(5):451-454.
[44]	Alvarez CS, Giménez R, Cañas MA, et al. Extracellular vesicles and soluble factors secreted by Escherichia coli Nissle 1917 and ECOR63 protect against enteropathogenic E. coli-induced intestinal epithelial barrier dysfunction[J]. BMC Microbiol, 2019, 19(1): 166. doi: 10.1186/s12866-019-1534-3
[45]	Wehkamp J, Harder J, Wehkamp K, et al. NF-κB- and AP-1-mediated induction of human beta defensin-2 in intestinal epithelial cells by Escherichia coli Nissle 1917: a novel effect of a probiotic bacterium[J]. Infect Immun, 2004, 72(10): 5750-5758. doi: 10.1128/IAI.72.10.5750-5758.2004 pmid: 15385474
[46]	Grabig A, Paclik D, Guzy C, et al. Escherichia coli strain Nissle 1917 ameliorates experimental colitis via toll-like receptor 2- and toll-like receptor 4-dependent pathways[J]. Infect Immun, 2006, 74(7): 4075-4082. doi: 10.1128/IAI.01449-05 pmid: 16790781
[47]	Gardlik R, Palffy R, Celec P. Recombinant probiotic therapy in experimental colitis in mice[J]. Folia Biol(Praha), 2012, 58(6): 238-245.
[48]	Oppong GO, Rapsinski GJ, Tursi SA, et al. Biofilm-associated bacterial amyloids dampen inflammation in the gut: oral treatment with curli fibres reduces the severity of hapten-induced colitis in mice[J]. NPJ Biofilms Microbiomes, 2015, 1: 15019. doi: 10.1038/npjbiofilms.2015.19 URL
[49]	Steimle A, Menz S, Bender A, et al. Flagellin hypervariable region determines symbiotic properties of commensal Escherichia coli strains[J]. PLoS Biol, 2019, 17(6): e3000334. doi: 10.1371/journal.pbio.3000334 URL
[50]	Behrouzi A, Mazaheri H, Falsafi S, et al. Intestinal effect of the probiotic Escherichia coli strain Nissle 1917 and its OMV[J]. J Diabetes Metab Disord, 2020, 19(1): 597-604. doi: 10.1007/s40200-020-00511-6
[51]	Shen QC, Huang ZZ, Yao JC, et al. Extracellular vesicles-mediated interaction within intestinal microenvironment in inflammatory bowel disease[J]. J Adv Res, 2021, 37: 221-233. doi: 10.1016/j.jare.2021.07.002 URL
[52]	Fábrega MJ, Rodríguez-Nogales A, Garrido-Mesa J, et al. Intestinal anti-inflammatory effects of outer membrane vesicles from Escherichia coli Nissle 1917 in DSS-experimental colitis in mice[J]. Front Microbiol, 2017, 8: 1274. doi: 10.3389/fmicb.2017.01274 URL
[53]	Cañas MA, Giménez R, Fábrega MJ, et al. Outer membrane vesicles from the probiotic Escherichia coli Nissle 1917 and the commensal ECOR12 enter intestinal epithelial cells via clathrin-dependent endocytosis and elicit differential effects on DNA damage[J]. PLoS One, 2016, 11(8): e0160374. doi: 10.1371/journal.pone.0160374 URL
[54]	Johansson MEV, Gustafsson JK, Holmén-Larsson J, et al. Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis[J]. Gut, 2014, 63(2): 281-291. doi: 10.1136/gutjnl-2012-303207 pmid: 23426893
[55]	Rodríguez-Nogales A, Algieri F, Garrido-Mesa J, et al. The administration of Escherichia coli Nissle 1917 ameliorates development of DSS-induced colitis in mice[J]. Front Pharmacol, 2018, 9: 468. doi: 10.3389/fphar.2018.00468 pmid: 29867475
[56]	Algieri F, Garrido-Mesa J, Vezza T, et al. Intestinal anti-inflammatory effects of probiotics in DNBS-colitis via modulation of gut microbiota and microRNAs[J]. Eur J Nutr, 2021, 60(5): 2537-2551. doi: 10.1007/s00394-020-02441-8
[57]	Chervy M, Barnich N, Denizot J. Adherent-invasive E. coli: update on the lifestyle of a troublemaker in Crohn's disease[J]. Int J Mol Sci, 2020, 21(10): 3734. doi: 10.3390/ijms21103734 URL
[58]	Zhang YZ, Li YY. Inflammatory bowel disease: Pathogenesis[J]. World J Gastroenterol, 2014, 20(1): 91-99. doi: 10.3748/wjg.v20.i1.91 URL
[59]	张维, 滕贵根, 田雨, 等. Elafin在炎症性肠病患者外周血中的表达及其临床意义[J]. 中华医学杂志, 2016, 96(14): 1120-1123.
	Zhang W, Teng GG, Tian Y, et al. Expression of elafin in peripheral blood in inflammatory bowel disease patients and its clinical significance[J]. Natl Med J China, 2016, 96(14): 1120-1123.
[60]	Zhang W, Teng GG, Wu T, et al. Expression and clinical significance of elafin in inflammatory bowel disease[J]. Inflamm Bowel Dis, 2017, 23(12): 2134-2141. doi: 10.1097/MIB.0000000000001252 pmid: 29084078
[61]	刘子麟, 王蔚虹, 刘芸, 等. 表达Elafin的益生菌Nissle 1917对小鼠实验性结肠炎的保护作用[J]. 中华医学杂志, 2021, 101(46): 3819-3824.
	Liu ZL, Wang W/YH, Liu Y, et al. Elafin-expressing probiotic Escherichia coli Nissle 1917 protects against experimental colitis[J]. Natl Med J China, 2021, 101(46): 3819-3824.
[62]	Fellermann K, Stange DE, Schaeffeler E, et al. A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon[J]. Am J Hum Genet, 2006, 79(3): 439-448. pmid: 16909382
[63]	Seo EJ, Weibel S, Wehkamp J, et al. Construction of recombinant E. coli Nissle 1917(EcN)strains for the expression and secretion of defensins[J]. Int J Med Microbiol, 2012, 302(6): 276-287. doi: 10.1016/j.ijmm.2012.05.002 URL
[64]	Praveschotinunt P, Duraj-Thatte AM, Gelfat I, et al. Engineered E. coli Nissle 1917 for the delivery of matrix-tethered therapeutic domains to the gut[J]. Nat Commun, 2019, 10(1): 5580. doi: 10.1038/s41467-019-13336-6 pmid: 31811125
[65]	Yu M, Kim J, Ahn JH, et al. Nononcogenic restoration of the intestinal barrier by E. coli-delivered human EGF[J]. JCI Insight, 2019, 4(16): e125166. doi: 10.1172/jci.insight.125166 URL
[66]	Taupin D, Podolsky DK. Trefoil factors: initiators of mucosal healing[J]. Nat Rev Mol Cell Biol, 2003, 4(9): 721-732.
[67]	Pai R, Tarnawski A. Signal transduction cascades triggered by EGF receptor activation: relevance to gastric injury repair and ulcer healing[J]. Dig Dis Sci, 1998, 43(9 Suppl): 14S-22S.
[68]	Yan X, Liu XY, Zhang D, et al. Construction of a sustainable 3-hydroxybutyrate-producing probiotic Escherichia coli for treatment of colitis[J]. Cell Mol Immunol, 2021, 18(10): 2344-2357. doi: 10.1038/s41423-021-00760-2 pmid: 34480146
[69]	Luo XM, Song HX, Yang J, et al. Encapsulation of Escherichia coli strain Nissle 1917 in a chitosan-alginate matrix by combining layer-by-layer assembly with CaCl₂ cross-linking for an effective treatment of inflammatory bowel diseases[J]. Colloids Surf B Biointerfaces, 2020, 189: 110818. doi: 10.1016/j.colsurfb.2020.110818 URL

动物模型 Model	研究目的 Aim	诱导物 Stimuli	持续时间 Duration/d	疗效 Therapeutic fffect	总结 Conclusion	参考文献 Reference
大鼠结肠炎模型	比较不同疗程、不同剂量的EcN对大鼠结肠炎的治疗作用	TNBS	15	低剂量EcN可治疗大鼠结肠炎，但长期服用大剂量EcN可能加重大鼠结肠炎的症状	EcN与不同抗生素联合使用时，具有协同治疗效果，但EcN可能存在产生抗生素耐药性的风险；单独口服一定量EcN具有治疗结肠炎的作用，但从多个试验结果表明，EcN能通过其他方式提高其治疗结肠炎的效果	[23]
大鼠结肠炎模型	比较利福昔明和EcN对大鼠结肠炎的治疗作用	乙酸溶液	8	利福昔明与EcN联合应用具有协同抗炎作用		[24]
小鼠结肠炎模型	探究EcN和米诺环素在小鼠复发性结肠炎中的关联	DSS	31	在米诺环素治疗过程中补充EcN可降低小鼠肠道炎症的损伤程度，防止实验性结肠炎的复发		[25]
小鼠结肠炎模型	评估预防性摄入EcN在小鼠结肠炎中的作用	DSS	28	小鼠预防性摄入EcN能改善结肠炎症状		[26]

动物模型 Model	研究目的 Aim	诱导物 Stimuli	持续时间 Duration/d	疗效 Therapeutic fffect	总结 Conclusion	参考文献 Reference
大鼠结肠炎模型	比较不同疗程、不同剂量的EcN对大鼠结肠炎的治疗作用	TNBS	15	低剂量EcN可治疗大鼠结肠炎，但长期服用大剂量EcN可能加重大鼠结肠炎的症状	EcN与不同抗生素联合使用时，具有协同治疗效果，但EcN可能存在产生抗生素耐药性的风险；单独口服一定量EcN具有治疗结肠炎的作用，但从多个试验结果表明，EcN能通过其他方式提高其治疗结肠炎的效果	[23]
大鼠结肠炎模型	比较利福昔明和EcN对大鼠结肠炎的治疗作用	乙酸溶液	8	利福昔明与EcN联合应用具有协同抗炎作用		[24]
小鼠结肠炎模型	探究EcN和米诺环素在小鼠复发性结肠炎中的关联	DSS	31	在米诺环素治疗过程中补充EcN可降低小鼠肠道炎症的损伤程度，防止实验性结肠炎的复发		[25]
小鼠结肠炎模型	评估预防性摄入EcN在小鼠结肠炎中的作用	DSS	28	小鼠预防性摄入EcN能改善结肠炎症状		[26]