芽囊原虫致病机制的研究进展
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摘要
芽囊原虫(Blastocystis)是常见的寄生于人和动物肠道的原生生物,但它是否具有致病性一直存在争议。临床调查发现,芽囊原虫感染与肠易激综合征(irritable bowel syndrome, IBS)、炎症性肠病(inflammatory bowel disease, IBD)以及免疫功能低下相关。芽囊原虫通过粪-口传播,主要寄居部位是盲肠和结肠,且芽囊原虫感染能引起细胞因子(IFN-γ、IL-12和TNF-α)上调及不同程度的肠道病理变化,但其致病机制尚不明确。近年来许多体外研究提出了芽囊原虫的几种致病机制,包括降解紧密连接蛋白引起肠上皮细胞通透性增加、细胞凋亡、上调肠道上皮细胞内的促炎细胞因子以及下调诱导型一氧化氮合酶(inducible nitric oxide synthase, iNOS)。本文就芽囊原虫致病机制的最新研究进行综述。
Blastocystis is a common enteric protozoan parasite of humans and many animals, but whether it is pathogenic or not is still controversial. Clinical studies show that Blastocystis is associated with the development of irritable bowel syndrome(IBS), inflammatory bowel disease(IBD) and immune dysfunction. Blastocystis is transmitted by the faecal-oral route, and it localizes mostly in the caecum and colon. In addition, Blastocystis infection may cause upregulation of cytokine(IFN-γ,IL-12 and TNF-α) expression and intestinal pathological changes with various degrees. But the pathogenesis of Blastocystis remains unclear. Recent years, many in vitro studies have proposed several pathogenic mechanisms of Blastocystis, including degradation of tight junction proteins resulting in increased intestinal permeability, apoptosis, upregulation of pro-inflammatory cytokines, and downregulation of inducible nitric oxide synthase. In this paper, we reviewed recent progress on the pathogenesis of Blastocystis.
Blastocystis is a common enteric protozoan parasite of humans and many animals, but whether it is pathogenic or not is still controversial. Clinical studies show that Blastocystis is associated with the development of irritable bowel syndrome(IBS), inflammatory bowel disease(IBD) and immune dysfunction. Blastocystis is transmitted by the faecal-oral route, and it localizes mostly in the caecum and colon. In addition, Blastocystis infection may cause upregulation of cytokine(IFN-γ,IL-12 and TNF-α) expression and intestinal pathological changes with various degrees. But the pathogenesis of Blastocystis remains unclear. Recent years, many in vitro studies have proposed several pathogenic mechanisms of Blastocystis, including degradation of tight junction proteins resulting in increased intestinal permeability, apoptosis, upregulation of pro-inflammatory cytokines, and downregulation of inducible nitric oxide synthase. In this paper, we reviewed recent progress on the pathogenesis of Blastocystis.
引文
[1] Tan KSW.New insights on classification,identification,and clinical relevance of Blastocystis spp[J].Clin Microbiol Rev,2008,21(4):639-665.DOI:10.1128/CMR.00022-08
[2] Parkar U,Traub RJ,Vitali S,et al.Molecular characterization of Blastocystis isolates from zoo animals and their animal-keepers[J].Vet Parasitol,2010,169(1):8-17.DOI:10.1016/j.vetpar.2009.12.032
[3] Roberts T,Stark D,Harkness J,et al.Update on the pathogenic potential and treatment options for Blastocystis sp[J].Gut Pathog,2014,6(1):17-25.DOI:10.1186/1757-4749-6-17
[4] Roberts T,Stark D,Harkness J,et al.Subtype distribution of Blastocystis isolates identified in a Sydney population and pathogenic potential of Blastocystis[J].Eur J Clin Microbiol Infect Dis,2013,32(3):335-343.DOI:10.1007/s10096-012-1746-z
[5] Alfellani MA,Taner-Mulla D,Jacob AS,et al.Genetic diversity of Blastocystis in livestock and zoo animals[J].Protist,2013,164(4):497-509.DOI:10.1016/j.protis.2013.05.003
[6] El SD,Gaayeb L,Meloni D,et al.Children of Senegal River Basin show the highest prevalence of Blastocystis sp.ever observed worldwide[J].BMC Infect Dis,2014,14(1):164-174.DOI:10.1186/1471-2334-14-164
[7] Stensvold CR,Clark CG.Current status of Blastocystis:A personal view[J].Parasitol Int,2016,65(6):763-771.DOI:10.1016/j.parint.2016.05.015
[8] Scanlan PD,Stensvold CR.Blastocystis:getting to grips with our guileful guest[J].Trends Parasitol,2013,29(11):523-529.DOI:10.1016/j.pt.2013.08.006
[9] Li LH,Zhang XP,Lv S,et al.Cross-sectional surveys and subtype classification of human Blastocystis isolates from four epidemiological settings in China[J].Parasitol Res,2007,102(1):83-90.DOI:10.1007/s00436-007-0727-0
[10] Poirier P,Wawrzyniak I,Vivarès CP,et al.New insights into Blastocystis spp.:a potential link with irritable bowel syndrome[J/OL].PLoS Pathog,2012,8(3):e1002545.DOI:10.1371/journal.ppat.1002545
[11] Stensvold CR,Nielsen HV,Molbak K,et al.Pursuing the clinical significance of Blastocystis-diagnostic limitations[J].Trends Parasitol,2009,25(1):23-29.DOI:10.1016/j.pt.2008.09.010
[12] Yakoob J,Jafri W,Beg MA,et al.Irritable bowel syndrome:is it associated with genotypes of Blastocystis hominis[J].Parasitol Res,2011,109(6):1745-1745.DOI:10.1007/s00436-010-1761-x
[13] Funda DA,Zahide S,Kenneth B,et al.Comparison of methods for detection of Blastocystis Infection in routinely submitted stool samples,and also in IBS/IBD patients in Ankara,Turkey[J/OL].PLoS ONE,2010,5(11):e15484.DOI:10.1371/journal.pone.0015484
[14] Yakoob J,Jafri W,Beg MA,et al.Blastocystis hominis and Dientamoeba fragilis in patients fulfilling irritable bowel syndrome criteria[J].Parasitol Res,2010,107(3):679-684.DOI:10.1007/s00436-010-1918-7
[15] Jesús K,Yamamoto-Furusho,Torijano-Carrera E.Intestinal protozoa infections among patients with ulcerative colitis:prevalence and impact on clinical disease course[J].Digestion,2010,82(1):18-23.DOI:10.1159/000273871
[16] Yoshikawa H,Yoshida K,Nakajima A,et al.Fecal-oral transmission of the cyst form of Blastocystis hominis in rats[J].Parasitol Res,2004,94(6):391-396.DOI:10.1007/s00436-004-1230-5
[17] Moe KT,Singh M,Howe J,et al.Experimental Blastocystis hominis infection in laboratory mice[J].Parasitol Res,1997,83(4):319-325.DOI:10.1007/s004360050256
[18] 张红卫,李文,颜秋叶,等.人芽囊原虫对实验感染昆明小鼠肠黏膜超微结构的影响[J].中国寄生虫学与寄生虫病杂志,2006,24(3):187-191.
[19] 姚繁荣,乔继英,赵晏,等.人芽囊原虫感染小鼠试验[J].中国寄生虫学与寄生虫病杂志,2005,23(6):444-448.
[20] Fayer R,Elsasser T,Gould R,et al.Blastocystis tropism in the pig intestine[J].Parasitol Res,2014,113(4):1465-1472.DOI:10.1007/s00436-014-3787-y
[21] Wang W,Bielefeldtohmann H,Traub RJ,et al.Location and pathogenic potential of Blastocystis in the porcine intestine[J/OL].Plos One,2014,9(8):e103962.DOI:10.1371/journal.pone.0103962
[22] Chandramathi S,Suresh KG,Mahmood AA,et al.Urinary hyaluronidase activity in rats infected with Blastocystis hominis-evidence for invasion?[J].Parasitol Res,2010,106(6):1459-1463.DOI:10.1007/s00436-010-1825-y
[23] Elwakil HS,Hewedi IH.Pathogenic potential of Blastocystis hominis in laboratory mice[J].Parasitol Res,2010,107(3):685-689.DOI:10.1007/s00436-010-1922-y
[24] Li J,Deng T,Li X,et al.A rat model to study Blastocytis subtype 1 infections[J].Parasitol Res,2013,112(10):3537-3541.DOI:10.1007/s00436-013-3536-7
[25] Hussein EM,Hussein AM,Eida MM,et al.Pathophysiological variability of different genotypes of human Blastocystis hominis,Egyptian isolates in experimentally infected rats[J].Parasitol Res,2008,102(5):853-860.DOI:10.1007/s00436-007-0833-z
[26] Iguchi A,Yoshikawa H,Yamada M,et al.Expression of interferon gamma and proinflammatory cytokines in the cecal mucosa of rats experimentally infected with Blastocystis sp.strain RN94-9[J].Parasitol Res,2009,105(1):135-140.DOI:10.1007/s00436-009-1373-5
[27] Yan Y,Su S,Lai R,et al.Genetic variability of Blastocystis hominis,isolates in China[J].Parasitol Res,2006,99(5):597-601.DOI:10.1007/s00436-006-0186-z
[28] Evans AS.Causation and disease:the Henle-Koch postulates revisited[J].Yale J Biol Med,1976,49(2):175-195.
[29] Mirza H,Wu Z,Teo J D,et al.Statin pleiotropy prevents rho kinase-mediated intestinal epithelial barrier compromise induced by Blastocystis cysteine proteases[J].Cell Microbiol,2012,14(9):1474-1484.DOI:10.1111/j.1462-5822.2012.01814.x
[30] Puthia MK,Sio SW,Lu J,et al.Blastocystis ratti induces contact-independent apoptosis,F-actin rearrangement,and barrier function disruption in IEC-6 cells[J].Infect Immun,2006,74(7):4114-4123.DOI:10.1128 /IAI.00328-06
[31] Wu B,Yin J,Texier C,et al.Blastocystis legumain is localized on the cell surface,and specific Inhibition of its activity implicates a pro-survival role for the enzyme[J].J Biol Chem,2010,285(3):1790-1798.DOI:10.1074/jbc.M109.049064
[32] Wu Z,Mirza H,Tan KSW.Intra-subtype variation in enteroadhesion accounts for differences in epithelial barrier disruption and is associated with metronidazole resistance in Blastocystis subtype-7[J/OL].PLoS Negl Trop Dis,2014,8(5):e2885.DOI:10.1371/journal.pntd.0002885
[33] Wu Z,Mirza H,Teo JD,et al.Strain-dependent induction of human enterocyte apoptosis by Blastocystis disrupts epithelial barrier and ZO-1 organization in a caspase 3- and 9-dependent manner[J/OL].Biomed Res Int,2014,2014(11):209163.DOI:10.1155/2014/209163
[34] Puthia MK,Vaithilingam A,Lu J,et al.Degradation of human secretory immunoglobulin A by Blastocystis[J].Parasitol Res,2005,97(5):386-389.DOI:10.1007/s00436-005-1461-0
[35] Mirza H,Wu Z,Kidwai F,et al.A metronidazole-resistant isolate of Blastocystis spp.is susceptible to nitric oxide and downregulates intestinal epithelial inducible nitric oxide synthase by a novel parasite survival mechanism[J].Infect Immun,2011,79(12):5019-5026.DOI:10.1007/s00436-005-1461-0
[36] Puthia M K,Lu J,Tan KS.Blastocystis ratti contains cysteine proteases that mediate interleukin-8 response from human intestinal epithelial cells in an NF-κB-dependent manner[J].Eukaryot Cell,2008,7(3):435-443.
[37] 伍玲园,符瑞佳,卢作超等.人芽囊原虫感染小鼠肠粘膜IL-17和IL-23的表达及意义[J].中国血吸虫病防治杂志,2012,24(6):676-680.
[38] Mei XL,Png CW,Tay CYB,et al.Differential regulation of proinflammatory cytokine Expression by mitogen-activated protein kinases in Macrophages in response to intestinal parasite infection[J].Infect Immun,2014,82(11):4789-4801.DOI:10.1128/IAI.02279-14
[39] Long H,Handschack A,Konig W,et al.Blastocystis hominis,modulates immune responses and cytokine release in colonic epithelial cells[J].Parasitol Res,2001,87(12):1029-1030.DOI:10.1007/s004360100494
[40] Ajjampur SS,Tan KS.Pathogenic mechanisms in Blastocystis spp.-interpreting results from in vitro and in vivo studies[J].Parasitol Int,2016,65(6):772-779.DOI:10.1016/j.parint.2016.05.007
[41] Nourrisson C,Wawrzyniak I,Cian A,et al.On Blastocystis secreted cysteine proteases:a legumain-activated cathepsin B increases paracellular permeability of intestinal Caco-2 cell monolayers[J].Parasitology,2016,143(13):1713-1722.DOI:10.1017/S0031182016001396
[42] Casén C,Veb H C,Sekelja M,et al.Deviations in human gut microbiota:a novel diagnostic test for determining dysbiosis in patients with IBS or IBD[J].Aliment Pharm Ther,2015,42(1):71-83.DOI:10.1111/apt.13236
[43] Nourrisson C,Scanzi J,Pereira B,et al.Blastocystis is associated with decrease of fecal microbiota protective bacteria:comparative analysis between patients with irritable bowel syndrome and control subjects[J/OL].PLoS ONE,2014,9(11):e111868.DOI:10.1371/journal.pone.0111868
[44] Bennet SM,Ohman L,Simren M.Gut microbiota as potential orchestrators of irritable bowel syndrome[J].Gut Liver,2015,9(3):318-331.DOI:10.5009/gnl14344
[45] Yamamotofurusho JK,Torijanocarrera E.Intestinal protozoa infections among patients with ulcerative colitis:prevalence and impact on clinical disease course[J].Digestion,2010,82(1):18-23.DOI:10.1159/000273871
[46] Audebert C,Even G,Cian A,et al.Colonization with the enteric protozoa Blastocystis is associated with increased diversity of human gut bacterial microbiota[J/OL].Sci Rep,2016,6:25255.DOI:10.1038/srep25255
[47] Stensvold CR.Thinking Blastocystis out of the box[J].Trends Parasitol,2012,28(8):305-305.DOI:10.1016/j.pt.2012.05.004
[2] Parkar U,Traub RJ,Vitali S,et al.Molecular characterization of Blastocystis isolates from zoo animals and their animal-keepers[J].Vet Parasitol,2010,169(1):8-17.DOI:10.1016/j.vetpar.2009.12.032
[3] Roberts T,Stark D,Harkness J,et al.Update on the pathogenic potential and treatment options for Blastocystis sp[J].Gut Pathog,2014,6(1):17-25.DOI:10.1186/1757-4749-6-17
[4] Roberts T,Stark D,Harkness J,et al.Subtype distribution of Blastocystis isolates identified in a Sydney population and pathogenic potential of Blastocystis[J].Eur J Clin Microbiol Infect Dis,2013,32(3):335-343.DOI:10.1007/s10096-012-1746-z
[5] Alfellani MA,Taner-Mulla D,Jacob AS,et al.Genetic diversity of Blastocystis in livestock and zoo animals[J].Protist,2013,164(4):497-509.DOI:10.1016/j.protis.2013.05.003
[6] El SD,Gaayeb L,Meloni D,et al.Children of Senegal River Basin show the highest prevalence of Blastocystis sp.ever observed worldwide[J].BMC Infect Dis,2014,14(1):164-174.DOI:10.1186/1471-2334-14-164
[7] Stensvold CR,Clark CG.Current status of Blastocystis:A personal view[J].Parasitol Int,2016,65(6):763-771.DOI:10.1016/j.parint.2016.05.015
[8] Scanlan PD,Stensvold CR.Blastocystis:getting to grips with our guileful guest[J].Trends Parasitol,2013,29(11):523-529.DOI:10.1016/j.pt.2013.08.006
[9] Li LH,Zhang XP,Lv S,et al.Cross-sectional surveys and subtype classification of human Blastocystis isolates from four epidemiological settings in China[J].Parasitol Res,2007,102(1):83-90.DOI:10.1007/s00436-007-0727-0
[10] Poirier P,Wawrzyniak I,Vivarès CP,et al.New insights into Blastocystis spp.:a potential link with irritable bowel syndrome[J/OL].PLoS Pathog,2012,8(3):e1002545.DOI:10.1371/journal.ppat.1002545
[11] Stensvold CR,Nielsen HV,Molbak K,et al.Pursuing the clinical significance of Blastocystis-diagnostic limitations[J].Trends Parasitol,2009,25(1):23-29.DOI:10.1016/j.pt.2008.09.010
[12] Yakoob J,Jafri W,Beg MA,et al.Irritable bowel syndrome:is it associated with genotypes of Blastocystis hominis[J].Parasitol Res,2011,109(6):1745-1745.DOI:10.1007/s00436-010-1761-x
[13] Funda DA,Zahide S,Kenneth B,et al.Comparison of methods for detection of Blastocystis Infection in routinely submitted stool samples,and also in IBS/IBD patients in Ankara,Turkey[J/OL].PLoS ONE,2010,5(11):e15484.DOI:10.1371/journal.pone.0015484
[14] Yakoob J,Jafri W,Beg MA,et al.Blastocystis hominis and Dientamoeba fragilis in patients fulfilling irritable bowel syndrome criteria[J].Parasitol Res,2010,107(3):679-684.DOI:10.1007/s00436-010-1918-7
[15] Jesús K,Yamamoto-Furusho,Torijano-Carrera E.Intestinal protozoa infections among patients with ulcerative colitis:prevalence and impact on clinical disease course[J].Digestion,2010,82(1):18-23.DOI:10.1159/000273871
[16] Yoshikawa H,Yoshida K,Nakajima A,et al.Fecal-oral transmission of the cyst form of Blastocystis hominis in rats[J].Parasitol Res,2004,94(6):391-396.DOI:10.1007/s00436-004-1230-5
[17] Moe KT,Singh M,Howe J,et al.Experimental Blastocystis hominis infection in laboratory mice[J].Parasitol Res,1997,83(4):319-325.DOI:10.1007/s004360050256
[18] 张红卫,李文,颜秋叶,等.人芽囊原虫对实验感染昆明小鼠肠黏膜超微结构的影响[J].中国寄生虫学与寄生虫病杂志,2006,24(3):187-191.
[19] 姚繁荣,乔继英,赵晏,等.人芽囊原虫感染小鼠试验[J].中国寄生虫学与寄生虫病杂志,2005,23(6):444-448.
[20] Fayer R,Elsasser T,Gould R,et al.Blastocystis tropism in the pig intestine[J].Parasitol Res,2014,113(4):1465-1472.DOI:10.1007/s00436-014-3787-y
[21] Wang W,Bielefeldtohmann H,Traub RJ,et al.Location and pathogenic potential of Blastocystis in the porcine intestine[J/OL].Plos One,2014,9(8):e103962.DOI:10.1371/journal.pone.0103962
[22] Chandramathi S,Suresh KG,Mahmood AA,et al.Urinary hyaluronidase activity in rats infected with Blastocystis hominis-evidence for invasion?[J].Parasitol Res,2010,106(6):1459-1463.DOI:10.1007/s00436-010-1825-y
[23] Elwakil HS,Hewedi IH.Pathogenic potential of Blastocystis hominis in laboratory mice[J].Parasitol Res,2010,107(3):685-689.DOI:10.1007/s00436-010-1922-y
[24] Li J,Deng T,Li X,et al.A rat model to study Blastocytis subtype 1 infections[J].Parasitol Res,2013,112(10):3537-3541.DOI:10.1007/s00436-013-3536-7
[25] Hussein EM,Hussein AM,Eida MM,et al.Pathophysiological variability of different genotypes of human Blastocystis hominis,Egyptian isolates in experimentally infected rats[J].Parasitol Res,2008,102(5):853-860.DOI:10.1007/s00436-007-0833-z
[26] Iguchi A,Yoshikawa H,Yamada M,et al.Expression of interferon gamma and proinflammatory cytokines in the cecal mucosa of rats experimentally infected with Blastocystis sp.strain RN94-9[J].Parasitol Res,2009,105(1):135-140.DOI:10.1007/s00436-009-1373-5
[27] Yan Y,Su S,Lai R,et al.Genetic variability of Blastocystis hominis,isolates in China[J].Parasitol Res,2006,99(5):597-601.DOI:10.1007/s00436-006-0186-z
[28] Evans AS.Causation and disease:the Henle-Koch postulates revisited[J].Yale J Biol Med,1976,49(2):175-195.
[29] Mirza H,Wu Z,Teo J D,et al.Statin pleiotropy prevents rho kinase-mediated intestinal epithelial barrier compromise induced by Blastocystis cysteine proteases[J].Cell Microbiol,2012,14(9):1474-1484.DOI:10.1111/j.1462-5822.2012.01814.x
[30] Puthia MK,Sio SW,Lu J,et al.Blastocystis ratti induces contact-independent apoptosis,F-actin rearrangement,and barrier function disruption in IEC-6 cells[J].Infect Immun,2006,74(7):4114-4123.DOI:10.1128 /IAI.00328-06
[31] Wu B,Yin J,Texier C,et al.Blastocystis legumain is localized on the cell surface,and specific Inhibition of its activity implicates a pro-survival role for the enzyme[J].J Biol Chem,2010,285(3):1790-1798.DOI:10.1074/jbc.M109.049064
[32] Wu Z,Mirza H,Tan KSW.Intra-subtype variation in enteroadhesion accounts for differences in epithelial barrier disruption and is associated with metronidazole resistance in Blastocystis subtype-7[J/OL].PLoS Negl Trop Dis,2014,8(5):e2885.DOI:10.1371/journal.pntd.0002885
[33] Wu Z,Mirza H,Teo JD,et al.Strain-dependent induction of human enterocyte apoptosis by Blastocystis disrupts epithelial barrier and ZO-1 organization in a caspase 3- and 9-dependent manner[J/OL].Biomed Res Int,2014,2014(11):209163.DOI:10.1155/2014/209163
[34] Puthia MK,Vaithilingam A,Lu J,et al.Degradation of human secretory immunoglobulin A by Blastocystis[J].Parasitol Res,2005,97(5):386-389.DOI:10.1007/s00436-005-1461-0
[35] Mirza H,Wu Z,Kidwai F,et al.A metronidazole-resistant isolate of Blastocystis spp.is susceptible to nitric oxide and downregulates intestinal epithelial inducible nitric oxide synthase by a novel parasite survival mechanism[J].Infect Immun,2011,79(12):5019-5026.DOI:10.1007/s00436-005-1461-0
[36] Puthia M K,Lu J,Tan KS.Blastocystis ratti contains cysteine proteases that mediate interleukin-8 response from human intestinal epithelial cells in an NF-κB-dependent manner[J].Eukaryot Cell,2008,7(3):435-443.
[37] 伍玲园,符瑞佳,卢作超等.人芽囊原虫感染小鼠肠粘膜IL-17和IL-23的表达及意义[J].中国血吸虫病防治杂志,2012,24(6):676-680.
[38] Mei XL,Png CW,Tay CYB,et al.Differential regulation of proinflammatory cytokine Expression by mitogen-activated protein kinases in Macrophages in response to intestinal parasite infection[J].Infect Immun,2014,82(11):4789-4801.DOI:10.1128/IAI.02279-14
[39] Long H,Handschack A,Konig W,et al.Blastocystis hominis,modulates immune responses and cytokine release in colonic epithelial cells[J].Parasitol Res,2001,87(12):1029-1030.DOI:10.1007/s004360100494
[40] Ajjampur SS,Tan KS.Pathogenic mechanisms in Blastocystis spp.-interpreting results from in vitro and in vivo studies[J].Parasitol Int,2016,65(6):772-779.DOI:10.1016/j.parint.2016.05.007
[41] Nourrisson C,Wawrzyniak I,Cian A,et al.On Blastocystis secreted cysteine proteases:a legumain-activated cathepsin B increases paracellular permeability of intestinal Caco-2 cell monolayers[J].Parasitology,2016,143(13):1713-1722.DOI:10.1017/S0031182016001396
[42] Casén C,Veb H C,Sekelja M,et al.Deviations in human gut microbiota:a novel diagnostic test for determining dysbiosis in patients with IBS or IBD[J].Aliment Pharm Ther,2015,42(1):71-83.DOI:10.1111/apt.13236
[43] Nourrisson C,Scanzi J,Pereira B,et al.Blastocystis is associated with decrease of fecal microbiota protective bacteria:comparative analysis between patients with irritable bowel syndrome and control subjects[J/OL].PLoS ONE,2014,9(11):e111868.DOI:10.1371/journal.pone.0111868
[44] Bennet SM,Ohman L,Simren M.Gut microbiota as potential orchestrators of irritable bowel syndrome[J].Gut Liver,2015,9(3):318-331.DOI:10.5009/gnl14344
[45] Yamamotofurusho JK,Torijanocarrera E.Intestinal protozoa infections among patients with ulcerative colitis:prevalence and impact on clinical disease course[J].Digestion,2010,82(1):18-23.DOI:10.1159/000273871
[46] Audebert C,Even G,Cian A,et al.Colonization with the enteric protozoa Blastocystis is associated with increased diversity of human gut bacterial microbiota[J/OL].Sci Rep,2016,6:25255.DOI:10.1038/srep25255
[47] Stensvold CR.Thinking Blastocystis out of the box[J].Trends Parasitol,2012,28(8):305-305.DOI:10.1016/j.pt.2012.05.004