粪菌移植的临床应用进展
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摘要
人类的肠道菌群种类和数量众多,肠道微生态失衡与炎症性肠病等多种疾病相关。肠道被认为是一个独立器官,在人体免疫系统发育和代谢平衡等系统中具有重要的作用。在我国古代就有应用粪便菌群移植(FMT)治疗疾病的记载。近年来,FMT成为研究热点,大量临床试验及循证医学证据表明FMT是治疗复发性难辨梭菌感染(r CDI)的有效方法,欧洲和北美的指南中也推荐将FMT用于抗生素治疗失败的r CDI,同时也可考虑将FMT用于与肠道生态失调相关的其他多种慢性疾病。
There are many types and numbers of human microbes( microbiota),and intestinal micro-ecological imbalance is associated with various diseases such as inflammatory bowel disease. The intestinal tract is considered to be an independent organ and plays an important role in the development of the body' s immune system and metabolic balance. There are records of the application of fecal microbiota transplantation( FMT) to treat diseases in ancient China. In recent years,FMT has become a research hotspot. A large number of clinical trials and evidence-based medicine suggest that FMT is an effective method for the treatment of recurrent Clostridium difficile infection( r CDI). The European and North American guidelines also recommend the use of FMT for r CDI that fails in the antibiotic treatment. At the same time,FMT can also be considered for a variety of other chronic diseases associated with intestinal ecological disorders.
There are many types and numbers of human microbes( microbiota),and intestinal micro-ecological imbalance is associated with various diseases such as inflammatory bowel disease. The intestinal tract is considered to be an independent organ and plays an important role in the development of the body' s immune system and metabolic balance. There are records of the application of fecal microbiota transplantation( FMT) to treat diseases in ancient China. In recent years,FMT has become a research hotspot. A large number of clinical trials and evidence-based medicine suggest that FMT is an effective method for the treatment of recurrent Clostridium difficile infection( r CDI). The European and North American guidelines also recommend the use of FMT for r CDI that fails in the antibiotic treatment. At the same time,FMT can also be considered for a variety of other chronic diseases associated with intestinal ecological disorders.
引文
[1]Zhang F,Luo W,Shi Y,et al.Should we standardize the 1,700-year-old fecal microbiota transplantation?[J].Am J Gastroenterol,2012,107(11):1755.
[2]Eiseman B,Silen W,Bascom GS,et al.Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis[J].Surgery,1958,44(5):854-859.
[3]Van Nood E,Vrieze A,Nieuwdorp M,et al.Duodenal infusion of donor feces for recurrent Clostridium difficile[J].N Engl J Med,2013,368(5):407-415.
[4]Smith M,Kassam Z,Edelstein C,et al.OpenBiome remains open to serve the medical community[J].Nat Biotechnol,2014,32(9):867.
[5]何植,张发明.中华粪菌库的原则,方案和风险管理[J].胃肠病学,2017,22(4):193-198.
[6]Khoruts A,Sadowsky MJ.Understanding the mechanisms of faecal microbiota transplantation[J].Nat Rev Gastroenterol Hepatol,2016,13(9):508-516.
[7]Allegretti JR,Kassam Z,Osman M,et al.The 5D framework:Aclinical primer for fecal microbiota transplantation to treat Clostridium difficile infection[J].Gastrointest Endosc,2018,87(1):18-29.
[8]Sadowsky MJ,Khoruts A.Faecal microbiota transplantation is promising but not a panacea[J].Nat Microbiol,2016,1:16015.
[9]Tang G,Yin W,Liu W.Is frozen fecal microbiota transplantation as effective as fresh fecal microbiota transplantation in patients with recurrent or refractory Clostridium difficile infection:A metaanalysis?[J].Diagn Microbiol Infect Dis,2017,88(4):322-329.
[10]Khanna S,Pardi DS,Kelly CR,et al.A novel microbiome therapeutic increases gut microbial diversity and prevents recurrent Clostridium difficile infection[J].J Infect Dis,2016,214(2):173-181.
[11]Cammarota G,Masucci L,Ianiro G,et al.Randomised clinical trial:Faecal microbiota transplantation by colonoscopy vs.vancomycin for the treatment of recurrent Clostridium difficile infection[J].Aliment Pharmacol Ther,2015,41(9):835-843.
[12]Khoruts A,Rank KM,Newman KM,et al.Inflammatory bowel disease affects the outcome of fecal microbiota transplantation for recurrent Clostridium difficile infection[J].Clin Gastroenterol Hepatol,2016,14(10):1433-1438.
[13]Mcdonald LC,Gerding DN,Johnson S,et al.Clinical practice guidelines for Clostridium difficile infection in adults and children:2017 update by the Infectious Diseases Society of America(IDSA)and Society for Healthcare Epidemiology of America(SHEA)[J].Clin Infect Dis,2018,66(7):e1-48.
[14]Leffler DA,Lamont JT.Clostridium difficile infection[J].N Engl J Med,2015,372(16):1539-1548.
[15]Kelly CP,Lamont JT.Clostridium difficile-More Difficult Than Ever[J].N Engl J Med,2008,359(18):1932-1940.
[16]Lessa FC,Mu Y,Bamberg WM,et al.Burden of Clostridium difficile infection in the United States[J].N Engl J Med,2015,372(9):825-834.
[17]Kelly BJ,Tebas P.Clinical practice and infrastructure review of fecal microbiota transplantation for Clostridium difficile infection[J].Chest,2018,153(1):266-277.
[18]Fischer M,Sipe B,Rogers N,et al.Faecal microbiota transplantation plus selected use of vancomycin for severe-complicated Clostridium difficile infection:Description of a protocol with high success rate[J].Aliment Pharmacol Ther,2015,42(4):470-476.
[19]Cammarota G,Ianiro G,Tilg H,et al.European consensus conference on faecal microbiota transplantation in clinical practice[J].Gut,2017,66(4):569-580.
[20]Kao D,Roach B,Silva M,et al.Effect of Oral Capsule-vs Colonoscopy-Delivered Fecal Microbiota Transplantation on Recurrent Clostridium difficile Infection:A Randomized Clinical Trial[J].JAMA,2017,318(20):1985-1993.
[21]Kelly CR,Khoruts A,Staley C,et al.Effect of Fecal Microbiota transplantation on recurrence in multiply recurrent Clostridium difficile infection:A randomized trial[J].Ann Intern Med,2016,165(9):609-616.
[22]Bennet J,Brinkman M.Treatment of ulcerative colitis by implantation of normal colonic flora[J].The Lancet,1989,1(8630):164.
[23]Paramsothy S,Kamm MA,Kaakoush NO,et al.Multidonor intensive faecal microbiota transplantation for active ulcerative colitis:A randomised placebo-controlled trial[J].The Lancet,2017,389(10075):1218-1228.
[24]Narula N,Kassam Z,Yuan Y,et al.Systematic Review and Metaanalysis:Fecal Microbiota Transplantation for Treatment of Active Ulcerative Colitis[J].Inflamm Bowel Dis,2017,23(10):1702-1709.
[25]Paramsothy S,Paramsothy R,Rubin DT,et al.Faecal microbiota transplantation for inflammatory bowel disease:A systematic review and meta-analysis[J].J Crohns Colitis,2017,11(10):1180-1199.
[26]Sun D,Li W,Li S,et al.Fecal microbiota transplantation as a novel therapy for ulcerative colitis:A systematic review and metaanalysis[J].Medicine,2016,95(23):e3765.
[27]Costello S,Soo W,Bryant R,et al.Systematic review with metaanalysis:Faecal microbiota transplantation for the induction of remission for active ulcerative colitis[J].Aliment Pharmacol Ther,2017,46(3):213-224.
[28]Nusbaum DJ,Sun F,Ren J,et al.Gut microbial and metabolomic profiles after fecal microbiota transplantation in pediatric ulcerative colitis patients[J].FEMS Microbiol Ecol,2018,94(9).
[29]Yodoshi T,Hurt TL.Fecal microbiota transplantation to patients with refractory very early onset ulcerative colitis[J].Pediatr Gastroenterol Hepatol Nutr,2018,21(4):355-360.
[30]Cui B,Feng Q,Wang H,et al.Fecal microbiota transplantation through mid-gut for refractory Crohn's disease:Safety,feasibility,and efficacy trial results[J].J Gastroenterol Hepatol,2015,30(1):51-58.
[31]Fang H,Fu L,Wang J.Protocol for fecal microbiota transplantation in inflammatory bowel disease:A systematic review and metaanalysis[J].Biomed Res Int,2018,2018:8941340.
[32]Rodi1o-Janeiro BK,Vicario M,Alonso-Cotoner C,et al.A review of microbiota and irritable bowel syndrome:Future in therapies[J].Adv Ther,2018,35(3):289-310.
[33]Schmulson M,Bashashati M.Fecal microbiota transfer for bowel disorders:Efficacy or hype?[J].Curr Opin Pharmacol,2018,43:72-80.
[34]Pinn DM,Aroniadis OC,Brandt LJ,et al.Is fecal microbiota transplantation the answer for irritable bowel syndrome?A singlecenter experience[J].Am J Gastroenterol,2014,109(11):1831-1832.
[35]Johnsen PH,Hilpusch F,Cavanagh JP,et al.Faecal microbiota transplantation versus placebo for moderate-to-severe irritable bowel syndrome:A double-blind,randomised,placebo-controlled,parallel-group,single-centre trial[J].Lancet Gastroenterol Hepatol,2018,3(1):17-24.
[36]Marotz CA,Zarrinpar A.Treating obesity and metabolic syndrome with fecal microbiota transplantation[J].Yale J Biol Med,2016,89(3):383-388.
[37]De Groot PF,Frissen MN.Fecal microbiota transplantation in metabolic syndrome:History,present and future[J].Gut Microbes,2017,8(3):253-267.
[38]Backhed F,Ding H,Wang T,et al.The gut microbiota as an environmental factor that regulates fat storage[J].Proc Natl Acad Sci U S A,2004,101(44):15718-15723.
[39]Kulecka M,Paziewska A,Zeber-Lubecka N,et al.Prolonged transfer of feces from the lean mice modulates gut microbiota in obese mice[J].Nutr Metab(Lond),2016,13(1):57.
[40]Ley RE,Backhed F,Turnbaugh P,et al.Obesity alters gut microbial ecology[J].Proc Natl Acad Sci U S A,2005,102(31):11070-11075.
[41]Ley RE,Turnbaugh PJ,Klein S,et al.Microbial ecology:Human gut microbes associated with obesity[J].Nature,2006,444(7122):1022-1023.
[42]Vrieze A,Van Nood E,Holleman F,et al.Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome[J].Gastroenterology,2012,143(4):913-916.
[43]Kakihana K,Fujioka Y,Suda W,et al.Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut[J].Blood,2016,128(16):2083-2088.
[44]Spindelboeck W,Schulz E,Uhl B,et al.Repeated fecal microbiota transplantations attenuate diarrhea and lead to sustained changes in the fecal microbiota in acute,refractory gastrointestinal graftversus-host-disease[J].Haematologica,2017,102(5):e210-213.
[45]Liu C,Frank DN,Horch M,et al.Associations between acute gastrointestinal Gv HD and the baseline gut microbiota of allogeneic hematopoietic stem cell transplant recipients and donors[J].Bone Marrow Transplant,2017,52(12):1643-1650.
[46]程敬伟,刘文恩,马小军,等.中国成人艰难梭菌感染诊断和治疗专家共识[J].协和医学杂志,2017,8(2):131-138.
[47]Wang S,Xu M,Wang W,et al.Systematic review:Adverse events of fecal microbiota transplantation[J].PLo S One,2016,11(8):e0161174.
[2]Eiseman B,Silen W,Bascom GS,et al.Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis[J].Surgery,1958,44(5):854-859.
[3]Van Nood E,Vrieze A,Nieuwdorp M,et al.Duodenal infusion of donor feces for recurrent Clostridium difficile[J].N Engl J Med,2013,368(5):407-415.
[4]Smith M,Kassam Z,Edelstein C,et al.OpenBiome remains open to serve the medical community[J].Nat Biotechnol,2014,32(9):867.
[5]何植,张发明.中华粪菌库的原则,方案和风险管理[J].胃肠病学,2017,22(4):193-198.
[6]Khoruts A,Sadowsky MJ.Understanding the mechanisms of faecal microbiota transplantation[J].Nat Rev Gastroenterol Hepatol,2016,13(9):508-516.
[7]Allegretti JR,Kassam Z,Osman M,et al.The 5D framework:Aclinical primer for fecal microbiota transplantation to treat Clostridium difficile infection[J].Gastrointest Endosc,2018,87(1):18-29.
[8]Sadowsky MJ,Khoruts A.Faecal microbiota transplantation is promising but not a panacea[J].Nat Microbiol,2016,1:16015.
[9]Tang G,Yin W,Liu W.Is frozen fecal microbiota transplantation as effective as fresh fecal microbiota transplantation in patients with recurrent or refractory Clostridium difficile infection:A metaanalysis?[J].Diagn Microbiol Infect Dis,2017,88(4):322-329.
[10]Khanna S,Pardi DS,Kelly CR,et al.A novel microbiome therapeutic increases gut microbial diversity and prevents recurrent Clostridium difficile infection[J].J Infect Dis,2016,214(2):173-181.
[11]Cammarota G,Masucci L,Ianiro G,et al.Randomised clinical trial:Faecal microbiota transplantation by colonoscopy vs.vancomycin for the treatment of recurrent Clostridium difficile infection[J].Aliment Pharmacol Ther,2015,41(9):835-843.
[12]Khoruts A,Rank KM,Newman KM,et al.Inflammatory bowel disease affects the outcome of fecal microbiota transplantation for recurrent Clostridium difficile infection[J].Clin Gastroenterol Hepatol,2016,14(10):1433-1438.
[13]Mcdonald LC,Gerding DN,Johnson S,et al.Clinical practice guidelines for Clostridium difficile infection in adults and children:2017 update by the Infectious Diseases Society of America(IDSA)and Society for Healthcare Epidemiology of America(SHEA)[J].Clin Infect Dis,2018,66(7):e1-48.
[14]Leffler DA,Lamont JT.Clostridium difficile infection[J].N Engl J Med,2015,372(16):1539-1548.
[15]Kelly CP,Lamont JT.Clostridium difficile-More Difficult Than Ever[J].N Engl J Med,2008,359(18):1932-1940.
[16]Lessa FC,Mu Y,Bamberg WM,et al.Burden of Clostridium difficile infection in the United States[J].N Engl J Med,2015,372(9):825-834.
[17]Kelly BJ,Tebas P.Clinical practice and infrastructure review of fecal microbiota transplantation for Clostridium difficile infection[J].Chest,2018,153(1):266-277.
[18]Fischer M,Sipe B,Rogers N,et al.Faecal microbiota transplantation plus selected use of vancomycin for severe-complicated Clostridium difficile infection:Description of a protocol with high success rate[J].Aliment Pharmacol Ther,2015,42(4):470-476.
[19]Cammarota G,Ianiro G,Tilg H,et al.European consensus conference on faecal microbiota transplantation in clinical practice[J].Gut,2017,66(4):569-580.
[20]Kao D,Roach B,Silva M,et al.Effect of Oral Capsule-vs Colonoscopy-Delivered Fecal Microbiota Transplantation on Recurrent Clostridium difficile Infection:A Randomized Clinical Trial[J].JAMA,2017,318(20):1985-1993.
[21]Kelly CR,Khoruts A,Staley C,et al.Effect of Fecal Microbiota transplantation on recurrence in multiply recurrent Clostridium difficile infection:A randomized trial[J].Ann Intern Med,2016,165(9):609-616.
[22]Bennet J,Brinkman M.Treatment of ulcerative colitis by implantation of normal colonic flora[J].The Lancet,1989,1(8630):164.
[23]Paramsothy S,Kamm MA,Kaakoush NO,et al.Multidonor intensive faecal microbiota transplantation for active ulcerative colitis:A randomised placebo-controlled trial[J].The Lancet,2017,389(10075):1218-1228.
[24]Narula N,Kassam Z,Yuan Y,et al.Systematic Review and Metaanalysis:Fecal Microbiota Transplantation for Treatment of Active Ulcerative Colitis[J].Inflamm Bowel Dis,2017,23(10):1702-1709.
[25]Paramsothy S,Paramsothy R,Rubin DT,et al.Faecal microbiota transplantation for inflammatory bowel disease:A systematic review and meta-analysis[J].J Crohns Colitis,2017,11(10):1180-1199.
[26]Sun D,Li W,Li S,et al.Fecal microbiota transplantation as a novel therapy for ulcerative colitis:A systematic review and metaanalysis[J].Medicine,2016,95(23):e3765.
[27]Costello S,Soo W,Bryant R,et al.Systematic review with metaanalysis:Faecal microbiota transplantation for the induction of remission for active ulcerative colitis[J].Aliment Pharmacol Ther,2017,46(3):213-224.
[28]Nusbaum DJ,Sun F,Ren J,et al.Gut microbial and metabolomic profiles after fecal microbiota transplantation in pediatric ulcerative colitis patients[J].FEMS Microbiol Ecol,2018,94(9).
[29]Yodoshi T,Hurt TL.Fecal microbiota transplantation to patients with refractory very early onset ulcerative colitis[J].Pediatr Gastroenterol Hepatol Nutr,2018,21(4):355-360.
[30]Cui B,Feng Q,Wang H,et al.Fecal microbiota transplantation through mid-gut for refractory Crohn's disease:Safety,feasibility,and efficacy trial results[J].J Gastroenterol Hepatol,2015,30(1):51-58.
[31]Fang H,Fu L,Wang J.Protocol for fecal microbiota transplantation in inflammatory bowel disease:A systematic review and metaanalysis[J].Biomed Res Int,2018,2018:8941340.
[32]Rodi1o-Janeiro BK,Vicario M,Alonso-Cotoner C,et al.A review of microbiota and irritable bowel syndrome:Future in therapies[J].Adv Ther,2018,35(3):289-310.
[33]Schmulson M,Bashashati M.Fecal microbiota transfer for bowel disorders:Efficacy or hype?[J].Curr Opin Pharmacol,2018,43:72-80.
[34]Pinn DM,Aroniadis OC,Brandt LJ,et al.Is fecal microbiota transplantation the answer for irritable bowel syndrome?A singlecenter experience[J].Am J Gastroenterol,2014,109(11):1831-1832.
[35]Johnsen PH,Hilpusch F,Cavanagh JP,et al.Faecal microbiota transplantation versus placebo for moderate-to-severe irritable bowel syndrome:A double-blind,randomised,placebo-controlled,parallel-group,single-centre trial[J].Lancet Gastroenterol Hepatol,2018,3(1):17-24.
[36]Marotz CA,Zarrinpar A.Treating obesity and metabolic syndrome with fecal microbiota transplantation[J].Yale J Biol Med,2016,89(3):383-388.
[37]De Groot PF,Frissen MN.Fecal microbiota transplantation in metabolic syndrome:History,present and future[J].Gut Microbes,2017,8(3):253-267.
[38]Backhed F,Ding H,Wang T,et al.The gut microbiota as an environmental factor that regulates fat storage[J].Proc Natl Acad Sci U S A,2004,101(44):15718-15723.
[39]Kulecka M,Paziewska A,Zeber-Lubecka N,et al.Prolonged transfer of feces from the lean mice modulates gut microbiota in obese mice[J].Nutr Metab(Lond),2016,13(1):57.
[40]Ley RE,Backhed F,Turnbaugh P,et al.Obesity alters gut microbial ecology[J].Proc Natl Acad Sci U S A,2005,102(31):11070-11075.
[41]Ley RE,Turnbaugh PJ,Klein S,et al.Microbial ecology:Human gut microbes associated with obesity[J].Nature,2006,444(7122):1022-1023.
[42]Vrieze A,Van Nood E,Holleman F,et al.Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome[J].Gastroenterology,2012,143(4):913-916.
[43]Kakihana K,Fujioka Y,Suda W,et al.Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut[J].Blood,2016,128(16):2083-2088.
[44]Spindelboeck W,Schulz E,Uhl B,et al.Repeated fecal microbiota transplantations attenuate diarrhea and lead to sustained changes in the fecal microbiota in acute,refractory gastrointestinal graftversus-host-disease[J].Haematologica,2017,102(5):e210-213.
[45]Liu C,Frank DN,Horch M,et al.Associations between acute gastrointestinal Gv HD and the baseline gut microbiota of allogeneic hematopoietic stem cell transplant recipients and donors[J].Bone Marrow Transplant,2017,52(12):1643-1650.
[46]程敬伟,刘文恩,马小军,等.中国成人艰难梭菌感染诊断和治疗专家共识[J].协和医学杂志,2017,8(2):131-138.
[47]Wang S,Xu M,Wang W,et al.Systematic review:Adverse events of fecal microbiota transplantation[J].PLo S One,2016,11(8):e0161174.