. 2014 Oct; 20(40):14805-20.
doi: 10.3748/wjg.v20.i40.14805.

Intestinal microbiota pathogenesis and fecal microbiota transplantation for inflammatory bowel disease

Zi-Kai Wang 1 Yun-Sheng Yang 1 Ye Chen 1 Jing Yuan 1 Gang Sun 1 Li-Hua Peng 1 
  • PMID: 25356041
  •     148 References
  •     36 citations


The intestinal microbiota plays an important role in inflammatory bowel disease (IBD). The pathogenesis of IBD involves inappropriate ongoing activation of the mucosal immune system driven by abnormal intestinal microbiota in genetically predisposed individuals. However, there are still no definitive microbial pathogens linked to the onset of IBD. The composition and function of the intestinal microbiota and their metabolites are indeed disturbed in IBD patients. The special alterations of gut microbiota associated with IBD remain to be evaluated. The microbial interactions and host-microbe immune interactions are still not clarified. Limitations of present probiotic products in IBD are mainly due to modest clinical efficacy, few available strains and no standardized administration. Fecal microbiota transplantation (FMT) may restore intestinal microbial homeostasis, and preliminary data have shown the clinical efficacy of FMT on refractory IBD or IBD combined with Clostridium difficile infection. Additionally, synthetic microbiota transplantation with the defined composition of fecal microbiota is also a promising therapeutic approach for IBD. However, FMT-related barriers, including the mechanism of restoring gut microbiota, standardized donor screening, fecal material preparation and administration, and long-term safety should be resolved. The role of intestinal microbiota and FMT in IBD should be further investigated by metagenomic and metatranscriptomic analyses combined with germ-free/human flora-associated animals and chemostat gut models.

Keywords: Fecal microbiota transplantation; Inflammatory bowel disease; Intestinal microbiota; Probiotics; Synthetic microbiota transplantation.

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Meta-analysis: the effect and adverse events of Lactobacilli versus placebo in maintenance therapy for Crohn disease.
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Helton Luis de Souza, Vanessa R de Carvalho, +3 authors, Josias Rodrigues.
Gut Pathog, 2012 Dec 14; 4(1). PMID: 23234341    Free PMC article.
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Reduced diversity and imbalance of fecal microbiota in patients with ulcerative colitis.
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Secukinumab failure in Crohn's disease: the yeast connection?
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Gut, 2012 Dec 13; 62(5). PMID: 23232049
Inflammatory bowel disease in Asia: a systematic review.
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J Gastroenterol Hepatol, 2012 Apr 14; 27(8). PMID: 22497584
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Inflamm Bowel Dis, 2009 Nov 04; 16(6). PMID: 19885905
Saccharomyces boulardii does not prevent relapse of Crohn's disease.
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A national survey of the prevalence and impact of Clostridium difficile infection among hospitalized inflammatory bowel disease patients.
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Am J Gastroenterol, 2008 Jun 03; 103(6). PMID: 18513271
Endoscopic fecal microbiota transplantation: "first-line" treatment for severe clostridium difficile infection?
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Fecal microbiota transplantation: current status and future directions.
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Expert Rev Gastroenterol Hepatol, 2011 Oct 25; 5(6). PMID: 22017691
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Br J Surg, 2000 Oct 24; 87(10). PMID: 11044159
The intestinal microbiota dysbiosis and Clostridium difficile infection: is there a relationship with inflammatory bowel disease?
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Therap Adv Gastroenterol, 2013 Jan 16; 6(1). PMID: 23320050    Free PMC article.
Increased prevalence of Methanosphaera stadtmanae in inflammatory bowel diseases.
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PLoS One, 2014 Feb 06; 9(2). PMID: 24498365    Free PMC article.
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Enterohepatic helicobacter in ulcerative colitis: potential pathogenic entities?
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PLoS One, 2011 Mar 09; 6(2). PMID: 21383845    Free PMC article.
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A pilot trial of Saccharomyces boulardii in ulcerative colitis.
Mario Guslandi, Patrizia Giollo, Pier Alberto Testoni.
Eur J Gastroenterol Hepatol, 2003 Jul 04; 15(6). PMID: 12840682
Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis.
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Gut, 2003 Dec 20; 53(1). PMID: 14684584    Free PMC article.
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Should we standardize the 1,700-year-old fecal microbiota transplantation?
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Am J Gastroenterol, 2012 Nov 20; 107(11). PMID: 23160295
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Metabolomics of fecal extracts detects altered metabolic activity of gut microbiota in ulcerative colitis and irritable bowel syndrome.
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J Proteome Res, 2011 Jul 19; 10(9). PMID: 21761941
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Cochrane Database Syst Rev, 2007 Oct 19; (4). PMID: 17943867
Systematic Review.
Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in children with ulcerative colitis.
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Am J Gastroenterol, 2009 Jan 29; 104(2). PMID: 19174792
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Microbiota dynamics in patients treated with fecal microbiota transplantation for recurrent Clostridium difficile infection.
Yang Song, Shashank Garg, +5 authors, W Florian Fricke.
PLoS One, 2013 Dec 05; 8(11). PMID: 24303043    Free PMC article.
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Altern Ther Health Med, 2011 May 28; 17(1). PMID: 21614946
Fungi and inflammatory bowel diseases: Alterations of composition and diversity.
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Characterization of adherent bacteroidales from intestinal biopsies of children and young adults with inflammatory bowel disease.
Naamah L Zitomersky, Benjamin J Atkinson, +4 authors, Athos Bousvaros.
PLoS One, 2013 Jun 19; 8(6). PMID: 23776434    Free PMC article.
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Role of Klebsiella and collagens in Crohn's disease: a new prospect in the use of low-starch diet.
Taha Rashid, Alan Ebringer, Harmale Tiwana, Mark Fielder.
Eur J Gastroenterol Hepatol, 2009 Apr 09; 21(8). PMID: 19352192
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Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients.
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Generating human intestinal tissues from pluripotent stem cells to study development and disease.
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Gut Microbiome: What We Do and Don't Know.
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A comprehensive review of the nasal microbiome in chronic rhinosinusitis (CRS).
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Crohn's Disease: Evolution, Epigenetics, and the Emerging Role of Microbiome-Targeted Therapies.
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Fecal Microbiota Transplantation: Current Applications, Effectiveness, and Future Perspectives.
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Progress in Our Understanding of the Gut Microbiome: Implications for the Clinician.
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Dissecting the Interplay Between Intestinal Microbiota and Host Immunity in Health and Disease: Lessons Learned from Germfree and Gnotobiotic Animal Models.
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Eur J Microbiol Immunol (Bp), 2016 Dec 17; 6(4). PMID: 27980855    Free PMC article.
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Antioxidant, Immunomodulating, and Microbial-Modulating Activities of the Sustainable and Ecofriendly Spirulina.
Alberto Finamore, Maura Palmery, Sarra Bensehaila, Ilaria Peluso.
Oxid Med Cell Longev, 2017 Feb 10; 2017. PMID: 28182098    Free PMC article.
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Mil Med Res, 2017 May 04; 4. PMID: 28465831    Free PMC article.
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Fecal microbiota transplantation for refractory Crohn's disease.
Seon Ho Bak, Hyun Ho Choi, +4 authors, Young-Seok Cho.
Intest Res, 2017 May 20; 15(2). PMID: 28522956    Free PMC article.
Faecal Microbiota Transplantation for Clostridium Difficile - a local perspective.
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Technical Aspects of Fecal Microbial Transplantation (FMT).
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Innate and Adaptive Cell Populations Driving Inflammation in Dry Eye Disease.
José L Reyes, Danielle T Vannan, +4 authors, Alicia Vázquez Mendoza.
Mediators Inflamm, 2018 Aug 31; 2018. PMID: 30158831    Free PMC article.
Fecal Microbiota Transplantation Ameliorates Experimentally Induced Colitis in Mice by Upregulating AhR.
Yan-Ling Wei, Yu-Qin Chen, +8 authors, Dong-Feng Chen.
Front Microbiol, 2018 Sep 11; 9. PMID: 30197631    Free PMC article.
Diarrhea as a Potential Cause and Consequence of Reduced Gut Microbial Diversity Among Undernourished Children in Peru.
Saba Rouhani, Nicholas W Griffin, +9 authors, Jeffrey I Gordon.
Clin Infect Dis, 2019 Nov 28; 71(4). PMID: 31773127    Free PMC article.
Therapeutic effects of lentinan on inflammatory bowel disease and colitis-associated cancer.
Yanrong Liu, Jianmin Zhao, +11 authors, Cheng Yang.
J Cell Mol Med, 2018 Nov 26; 23(2). PMID: 30472806    Free PMC article.
Fecal Microbial Transplantation and Its Potential Application in Cardiometabolic Syndrome.
Avner Leshem, Nir Horesh, Eran Elinav.
Front Immunol, 2019 Jul 02; 10. PMID: 31258528    Free PMC article.
Individual and cohort-specific gut microbiota patterns associated with tissue-specific insulin sensitivity in overweight and obese males.
Gerben D A Hermes, Dorien Reijnders, +5 authors, Erwin G Zoetendal.
Sci Rep, 2020 May 07; 10(1). PMID: 32371932    Free PMC article.
Characteristics of Fecal Microbiota Transplantation Use in Inflammatory Bowel Disease Cohort.
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Crohns Colitis 360, 2020 May 19; 2(2). PMID: 32421761    Free PMC article.
Gut microbiota modulation: a novel strategy for prevention and treatment of colorectal cancer.
Winnie Fong, Qing Li, Jun Yu.
Oncogene, 2020 Jun 10; 39(26). PMID: 32514151    Free PMC article.
Fecal microbiota transplantation: donor relation, fresh or frozen, delivery methods, cost-effectiveness.
Daryl Ramai, Karl Zakhia, +2 authors, Madhavi Reddy.
Ann Gastroenterol, 2019 Jan 02; 32(1). PMID: 30598589    Free PMC article.
Carbapenemases in Enterobacteriaceae: Detection and Antimicrobial Therapy.
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Front Microbiol, 2019 Sep 05; 10. PMID: 31481937    Free PMC article.
Association Between Impaired Vα7.2+CD161++CD8+ (MAIT) and Vα7.2+CD161-CD8+ T-Cell Populations and Gut Dysbiosis in Chronically HIV- and/or HCV-Infected Patients.
Esther Merlini, Maddalena Cerrone, +5 authors, Giulia Marchetti.
Front Microbiol, 2019 Sep 27; 10. PMID: 31555223    Free PMC article.
Fecal microbiota transplantation in refractory ulcerative colitis - a case report.
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J Int Med Res, 2019 Jan 12; 47(2). PMID: 30632438    Free PMC article.
Hypoglycemic Mechanism of the Berberine Organic Acid Salt under the Synergistic Effect of Intestinal Flora and Oxidative Stress.
Hong-Xin Cui, Ya-Nan Hu, Jing-Wan Li, Ke Yuan.
Oxid Med Cell Longev, 2019 Jan 22; 2018. PMID: 30662584    Free PMC article.
The Intestinal Microbiota and Colorectal Cancer.
Yiwen Cheng, Zongxin Ling, Lanjuan Li.
Front Immunol, 2020 Dec 18; 11. PMID: 33329610    Free PMC article.
Fecal microbiota transplantation for COVID-19; a potential emerging treatment strategy.
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Med Hypotheses, 2021 Jan 23; 147. PMID: 33482620    Free PMC article.
Clinical efficacy of fecal microbiota transplantation for patients with small intestinal bacterial overgrowth: a randomized, placebo-controlled clinic study.
Fenghua Xu, Ning Li, +3 authors, Yanling Wei.
BMC Gastroenterol, 2021 Feb 08; 21(1). PMID: 33549047    Free PMC article.
Effect of berberine on hyperglycaemia and gut microbiota composition in type 2 diabetic Goto-Kakizaki rats.
Jin-Dong Zhao, Yan Li, +10 authors, Zhao-Hui Fang.
World J Gastroenterol, 2021 Mar 16; 27(8). PMID: 33716449    Free PMC article.
Fermented Maillard Reaction Products by Lactobacillus gasseri 4M13 Alters the Intestinal Microbiota and Improves Dysfunction in Type 2 Diabetic Mice with Colitis.
Yu-Jin Jeong, Ho-Young Park, Han-Kyul Nam, Kwang-Won Lee.
Pharmaceuticals (Basel), 2021 Apr 04; 14(4). PMID: 33800583    Free PMC article.
A Link between Chronic Kidney Disease and Gut Microbiota in Immunological and Nutritional Aspects.
Paulina Mertowska, Sebastian Mertowski, +4 authors, Wojciech Załuska.
Nutrients, 2021 Oct 24; 13(10). PMID: 34684638    Free PMC article.
In vitro Prebiotic Effect of Bread-Making Process in Inflammatory Bowel Disease Microbiome.
Aleix Lluansí, Marc Llirós, +20 authors, Xavier Aldeguer.
Front Microbiol, 2021 Oct 29; 12. PMID: 34707578    Free PMC article.