粪菌移植在临床治疗中的研究进展
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摘要
粪菌移植的历史可以追溯到中国东晋时期。大量研究证实粪菌移植有可能成为许多疾病的有效治疗方法,现已逐渐应用于临床上并取得较好的疗效。粪菌移植可以通过增加短链脂肪酸,特别是丁酸盐的产量来减少肠道通透性,从而降低疾病的严重程度,这有助于维持上皮屏障的完整性。粪菌移植还可以通过抑制Th1分化、T细胞活性、白细胞粘附和炎症因子的产生来恢复免疫生态失调。目前对粪菌移植的研究主要集中在治疗艰难梭菌感染,但其他领域对粪菌移植研究的热情也日益高涨,如用于治疗炎症性肠病、代谢综合征和肠易激综合征等。本文对最新的粪菌移植在临床治疗中的研究进展作一综述。
The history of fecal microbiota transplantation can be traced back to the period of the eastern Jin dynasty in China.Many studies have shown that fecal microbiota transplantation may be an effective treatment for many diseases,which has been gradually applied clinically and got good results.Fecal microbiota transplantation can reduce bowel permeability and thus the severity of the disease by increasing the production of short-chain fatty acids,especially butyrate which help maintain the integrity of the epithelial barrier.Fecal microbiota transplantation can also restore immune dysbiosis by inhibiting Th1 differentiation,activity of T cells,leukocyte adhesion,and production of inflammatory factors.At present,the research on fecal microbiota transplantation is mainly focused on Clostridium difficile infection.But in other fields,the enthusiasm for the study on fecal microbiota transplantation is increasing;for example,fecal microbiota transplantation has been used to treat inflammatory bowel disease,metabolic syndrome and irritable bowel syndrome.This article reviews the latest progress in research on fecal bacterium transplantation in clinical treatment.
The history of fecal microbiota transplantation can be traced back to the period of the eastern Jin dynasty in China.Many studies have shown that fecal microbiota transplantation may be an effective treatment for many diseases,which has been gradually applied clinically and got good results.Fecal microbiota transplantation can reduce bowel permeability and thus the severity of the disease by increasing the production of short-chain fatty acids,especially butyrate which help maintain the integrity of the epithelial barrier.Fecal microbiota transplantation can also restore immune dysbiosis by inhibiting Th1 differentiation,activity of T cells,leukocyte adhesion,and production of inflammatory factors.At present,the research on fecal microbiota transplantation is mainly focused on Clostridium difficile infection.But in other fields,the enthusiasm for the study on fecal microbiota transplantation is increasing;for example,fecal microbiota transplantation has been used to treat inflammatory bowel disease,metabolic syndrome and irritable bowel syndrome.This article reviews the latest progress in research on fecal bacterium transplantation in clinical treatment.
引文
[1]Fischer M,Sipe BW,Rogers NA,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.
[2]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.
[3]Agrawal M,Aroniadis OC,Brandt LJ,et al.The Long-term efficacy and safety of fecal microbiota transplant for recurrent,severe,and complicated Clostridium difficile infection in 146elderly individuals[J].J Clin Gastroenterol,2016,50(5):403-407.
[4]Fischer M,Kao D,Mehta SR,et al.Predictors of early failure after fecal microbiota transplantation for the therapy of Clostridium difficile infection:A multicenter study[J].Am JGastroenterol,2016,111(7):1024-1031.
[5]Zowall H,Brewer C,Deutsch A.Cost-effectiveness of fecal microbiota transplant in treating Clostridium difficile infection in Canada[J].Value Health,2014,17(7):A676.
[6]Surawicz CM,Brandt LJ,Binion DG,et al.Guidelines for diagnosis,treatment,and prevention of Clostridium difficile infections[J].Am J Gastroenterol,2013,108(4):478-498.
[7]Kunde S,Pham A,Bonczyk S,et al.Safety,tolerability,and clinical response after fecal transplantation in children and young adults with ulcerative colitis[J].J Pediatr Gastroenterol Nutr,2013,56(6):597-601.
[8]Kellermayer R,Nagy-Szakal D,Harris RA,et al.Serial fecal microbiota transplantation alters mucosal gene expression in pediatric ulcerative colitis[J].Am J Gastroenterol,2015,110(4):604-606.
[9]Wei Y,Zhu W,Gong J,et al.Fecal microbiota transplantation improves the quality of life in patients with inflammatory bowel disease[J].Gastroenterol Res Pract,2015,2015:517597.
[10]Kump PK,Gr9chenig HP,Lackner S,et al.Alteration of intestinal dysbiosis by fecal microbiota transplantation does not induce remission in patients with chronic active ulcerative colitis[J].Inflamm Bowel Dis,2013,19(10):2155-2165.
[11]Angelberger S,Reinisch W,Makristathis A,et al.Temporal bacterial community dynamics vary among ulcerative colitis patients after fecal microbiota transplantation[J].Am J Gastroenterol,2013,108(10):1620-1630.
[12]Rossen NG,Fuentes S,van der Spek MJ,et al.Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis[J].Gastroenterology,2015,149(1):110-118.
[13]Moayyedi P,Surette MG,Kim PT,et al.Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial[J].Gastroenterology,2015,149(1):102-109.
[14]Paramsothy S,Kamm MA,Kaakoush NO,et al.Multidonor intensive faecal microbiota transplantation for active ulcerative colitis:A randomised placebo-controlled trial[J].Lancet,2017,389(10075):1218-1228.
[15]Sun D,Li W,Li S,et al.Fecal microbiota transplantation as a novel therapy for ulcerative colitis:A systematic review and meta-analysis[J].Medicine(Baltimore),2016,95(23):e3765.
[16]Cui B,Li P,Xu L,et al.Step-up fecal microbiota transplantation strategy:A pilot study for steroid-dependent ulcerative colitis[J].J Transl Med,2015,13:298.
[17]Colman RJ,Rubin DT.Fecal microbiota transplantation as therapy for inflammatory bowel disease:A systematic review and meta-analysis[J].J Crohns Colitis,2014,8(12):1569-1581.
[18]Arumugam M,Raes J,Pelletier E,et al.Enterotypes of the human gut microbiome[J].Nature,2011,473(7346):174-180.
[19]Karlsson FH,Tremaroli V,Nookaew I,et al.Gut metagenome in European women with normal,impaired and diabetic glucose control[J].Nature,2013,498(7452):99-103.
[20]Bckhed 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.
[21]Ridaura VK,Faith JJ,Rey FE,et al.Gut microbiota from twins discordant for obesity modulate metabolism in mice[J].Science,2013,341(6150):1241214.
[22]Alang N,Kelly CR.Weight gain after fecal microbiota transplantation[J].Open Forum Infect Dis,2015,2(1):ofv004.
[23]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.
[24]Lovell RM,Ford AC.Global prevalence of and risk factors for irritable bowel syndrome:A meta-analysis[J].Clin Gastroenterol Hepatol,2012,10(7):712-721.
[25]Tap J,Derrien M,T9rnblom H,et al.Identification of an intestinal microbiota signature associated with severity of irritable bowel syndrome[J].Gastroenterology,2017,152(1):111-123.
[26]Mizuno S,Masaoka T,Naganuma M,et al.Bifidobacteriumrich fecal donor may be a positive predictor for successful fecal microbiota transplantation in patients with irritable bowel syndrome[J].Digestion,2017,96(1):29-38.
[27]Kurokawa S,Kishimoto T,Mizuno S,et al.The effect of fecal microbiota transplantation on psychiatric symptoms among patients with irritable bowel syndrome,functional diarrhea and functional constipation:An open-label observational study[J].J Affect Disord,2018,235:506-512.
[28]Halkjr SI,Boolsen AW,Günther S,et al.Can fecal microbiota transplantation cure irritable bowel syndrome[J].World JGastroenterol,2017,23(22):4112-4120.
[29]Pamer EG.Fecal microbiota transplantation:Effectiveness,complexities,and lingering concerns[J].Mucosal Immunol,2014,7(2):210-214.
[30]Khoruts A,Weingarden AR.Emergence of fecal microbiota transplantation as an approach to repair disrupted microbial gut ecology[J].Immunol Lett,2014,162(2Pt A):77-81.
[31]Woting A,Blaut M.The intestinal microbiota in metabolic disease[J].Nutrients,2016,8(4):202.
[32]Dutta SK,Girotra M,Garg S,et al.Efficacy of combined jejunal and colonic fecal microbiota transplantation for recurrent Clostridium difficile Infection[J].Clin Gastroenterol Hepatol,2014,12(9):1572-1576.
[2]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.
[3]Agrawal M,Aroniadis OC,Brandt LJ,et al.The Long-term efficacy and safety of fecal microbiota transplant for recurrent,severe,and complicated Clostridium difficile infection in 146elderly individuals[J].J Clin Gastroenterol,2016,50(5):403-407.
[4]Fischer M,Kao D,Mehta SR,et al.Predictors of early failure after fecal microbiota transplantation for the therapy of Clostridium difficile infection:A multicenter study[J].Am JGastroenterol,2016,111(7):1024-1031.
[5]Zowall H,Brewer C,Deutsch A.Cost-effectiveness of fecal microbiota transplant in treating Clostridium difficile infection in Canada[J].Value Health,2014,17(7):A676.
[6]Surawicz CM,Brandt LJ,Binion DG,et al.Guidelines for diagnosis,treatment,and prevention of Clostridium difficile infections[J].Am J Gastroenterol,2013,108(4):478-498.
[7]Kunde S,Pham A,Bonczyk S,et al.Safety,tolerability,and clinical response after fecal transplantation in children and young adults with ulcerative colitis[J].J Pediatr Gastroenterol Nutr,2013,56(6):597-601.
[8]Kellermayer R,Nagy-Szakal D,Harris RA,et al.Serial fecal microbiota transplantation alters mucosal gene expression in pediatric ulcerative colitis[J].Am J Gastroenterol,2015,110(4):604-606.
[9]Wei Y,Zhu W,Gong J,et al.Fecal microbiota transplantation improves the quality of life in patients with inflammatory bowel disease[J].Gastroenterol Res Pract,2015,2015:517597.
[10]Kump PK,Gr9chenig HP,Lackner S,et al.Alteration of intestinal dysbiosis by fecal microbiota transplantation does not induce remission in patients with chronic active ulcerative colitis[J].Inflamm Bowel Dis,2013,19(10):2155-2165.
[11]Angelberger S,Reinisch W,Makristathis A,et al.Temporal bacterial community dynamics vary among ulcerative colitis patients after fecal microbiota transplantation[J].Am J Gastroenterol,2013,108(10):1620-1630.
[12]Rossen NG,Fuentes S,van der Spek MJ,et al.Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis[J].Gastroenterology,2015,149(1):110-118.
[13]Moayyedi P,Surette MG,Kim PT,et al.Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial[J].Gastroenterology,2015,149(1):102-109.
[14]Paramsothy S,Kamm MA,Kaakoush NO,et al.Multidonor intensive faecal microbiota transplantation for active ulcerative colitis:A randomised placebo-controlled trial[J].Lancet,2017,389(10075):1218-1228.
[15]Sun D,Li W,Li S,et al.Fecal microbiota transplantation as a novel therapy for ulcerative colitis:A systematic review and meta-analysis[J].Medicine(Baltimore),2016,95(23):e3765.
[16]Cui B,Li P,Xu L,et al.Step-up fecal microbiota transplantation strategy:A pilot study for steroid-dependent ulcerative colitis[J].J Transl Med,2015,13:298.
[17]Colman RJ,Rubin DT.Fecal microbiota transplantation as therapy for inflammatory bowel disease:A systematic review and meta-analysis[J].J Crohns Colitis,2014,8(12):1569-1581.
[18]Arumugam M,Raes J,Pelletier E,et al.Enterotypes of the human gut microbiome[J].Nature,2011,473(7346):174-180.
[19]Karlsson FH,Tremaroli V,Nookaew I,et al.Gut metagenome in European women with normal,impaired and diabetic glucose control[J].Nature,2013,498(7452):99-103.
[20]Bckhed 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.
[21]Ridaura VK,Faith JJ,Rey FE,et al.Gut microbiota from twins discordant for obesity modulate metabolism in mice[J].Science,2013,341(6150):1241214.
[22]Alang N,Kelly CR.Weight gain after fecal microbiota transplantation[J].Open Forum Infect Dis,2015,2(1):ofv004.
[23]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.
[24]Lovell RM,Ford AC.Global prevalence of and risk factors for irritable bowel syndrome:A meta-analysis[J].Clin Gastroenterol Hepatol,2012,10(7):712-721.
[25]Tap J,Derrien M,T9rnblom H,et al.Identification of an intestinal microbiota signature associated with severity of irritable bowel syndrome[J].Gastroenterology,2017,152(1):111-123.
[26]Mizuno S,Masaoka T,Naganuma M,et al.Bifidobacteriumrich fecal donor may be a positive predictor for successful fecal microbiota transplantation in patients with irritable bowel syndrome[J].Digestion,2017,96(1):29-38.
[27]Kurokawa S,Kishimoto T,Mizuno S,et al.The effect of fecal microbiota transplantation on psychiatric symptoms among patients with irritable bowel syndrome,functional diarrhea and functional constipation:An open-label observational study[J].J Affect Disord,2018,235:506-512.
[28]Halkjr SI,Boolsen AW,Günther S,et al.Can fecal microbiota transplantation cure irritable bowel syndrome[J].World JGastroenterol,2017,23(22):4112-4120.
[29]Pamer EG.Fecal microbiota transplantation:Effectiveness,complexities,and lingering concerns[J].Mucosal Immunol,2014,7(2):210-214.
[30]Khoruts A,Weingarden AR.Emergence of fecal microbiota transplantation as an approach to repair disrupted microbial gut ecology[J].Immunol Lett,2014,162(2Pt A):77-81.
[31]Woting A,Blaut M.The intestinal microbiota in metabolic disease[J].Nutrients,2016,8(4):202.
[32]Dutta SK,Girotra M,Garg S,et al.Efficacy of combined jejunal and colonic fecal microbiota transplantation for recurrent Clostridium difficile Infection[J].Clin Gastroenterol Hepatol,2014,12(9):1572-1576.