Our intestinal microbiota comprises 100 trillion bacteria, exceeding our own eukaryotic cells. While the microbiota has incredible health benefits, changes in the normal flora caused by inflammation, antibiotics or diet can negatively impact health and may contribute to diseases such as inflammatory bowel disease (IBD) and obesity. Using healthy microbiota to treat individuals with intestinal disease is not a new idea and fecal microbiota transplantation (FMT) has been used as a successful therapy in patients suffering from Clostridium difficile infection. Currently FMT is being considered as a treatment for patients with IBD. This editorial will discuss the history of FMT and implications for treatment of other inflammatory intestinal diseases

Jee-Hyun Kim

R. William DePaolo

English

Our intestinal microbiota comprises 100 trillion bacteria, exceeding our own eukaryotic cells. While the microbiota has incredible health benefits, changes in the normal flora caused by inflammation, antibiotics or diet can negatively impact health and may contribute to diseases such as inflammatory bowel disease (IBD) and obesity. Using healthy microbiota to treat individuals with intestinal disease is not a new idea and fecal microbiota transplantation (FMT) has been used as a successful therapy in patients suffering from Clostridium difficile infection. Currently FMT is being considered as a treatment for patients with IBD. This editorial will discuss the history of FMT and implications for treatment of other inflammatory intestinal diseases.Editorial | Biohelikon: Immunity and Diseases

ZENODO

1Biohelikon: Immunity & Diseases, 2013 1:3EditorialFecal microbiota transplantation as an alternativetreatment for infection and inﬂammationJee-Hyun Kim1, R. William DePaolo1*1Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA 90089*Corresponding author, Email: depaolo@usc.eduAbstractOur intestinal microbiota comprises 100 trillion bacteria, exceeding our own eukaryotic cells. While the microbiota has incrediblehealth beneﬁts, changes in the normal ﬂora caused by inﬂammation, antibiotics or diet can negatively impact health and maycontribute to diseases such as inﬂammatory bowel disease (IBD) and obesity. Using healthy microbiota to treat individuals withintestinal disease is not a new idea and fecal microbiota transplantation (FMT) has been used as a successful therapy in patientssuﬀering from Clostridium diﬃcile infection. Currently FMT is being considered as a treatment for patients with IBD. This editorialwill discuss the history of FMT and implications for treatment of other inﬂammatory intestinal diseases.KeywordsMicrobiota, IBD, C. diﬃcile, mucosal immunityAbbreviationFMT: Fecal Microbiota Transplantation Our gut microbiota comprises 100 trillion bacteria,exceeding our own cells by ten-fold. The gutmicrobiota has several functions, including digestion,colonization resistance, maintenance of mucosalintegrity, and priming of the mucosal immuneresponse [1]. Disruption of the normal microbiota,or dysbiosis, can impact immunity and result indisease. This is best illustrated by Clostridiumdiﬃcile infection (CDI), acquired when gut microbialdiversity and number are reduced by antibiotictreatment. Antibiotic treatment compromises theability of the natural microbiota to resist colonizationby opportunistic pathogens, allowing resident C.diﬃcile or ingested environmental C. diﬃcile sporesto dominate the intestinal tract, which leadsto diarrhea and inﬂammation associated withpseudomembranous colitis. The close relationshipbetween gut microbiota and disease is also apparentin IBD, such as Crohn’s disease and ulcerative colitis,and alterations in the microbiota of IBD patients arewell documented [2-11].C. diﬃcile is one of the most important causesof nosocomial infections. In the last 10 - 15 years,with the emergence of hypervirulent strains, therehas been an increase in prevalence and severityof CDI [12]. Standard treatment for CDI involvesantibiotics such as metronidazole and vancomycin.However, ~20 % of patients with an initial CDIare unresponsive to antibiotic treatment [13,14].Furthermore, despite the recommended treatment,recurrence of disease is frequent [13-15]. Thereare now alternative antibiotics such as ﬁdaxomicin,which has a CDI cure rate similar to vancomycin andshows improvement in its eﬃcacy against recurrentCDI [16,17].FMT is beginning to be recognized as analternative to antibiotic treatment for CDI. FMTinvolves infusing bacteria from a healthy donor intothe gastrointestinal tract of the patient to reestablisha normal gut ﬂora by repairing or replacing thediseased ﬂora [18]. In veterinary medicine, thisprocess, called transfaunation, has been practicedfor decades [19]. The ﬁrst recorded performance ofFMT in humans was in the 1950s in patients withfulminant pseudomembranous colitis later foundto be caused by recalcitrant CDI, who showed“immediate and dramatic” responses [20]. Todaythere are more than 500 patients who have beentreated for CDI with FMT with a cure rate of~95% [21,22]. However, despite its eﬃcacy, FMThas not become a widely used therapy for CDI,mainly due to the “yuck factor” and lack of datafrom randomized, controlled trials. Earlier this year,eﬃcacy of FMT for recurrent CDI was conﬁrmedby the ﬁrst randomized, controlled trial [23]. Inthis study, FMT was signiﬁcantly more eﬀective intreating recurrent CDI than vancomycin alone or incombination with bowel lavage. Although the trialwas not blinded and had a small group size, itprovides impetus to address the other obstacles inadopting FMT as a routine therapy. As an example,there is growing interest in strategies to circumventthe direct use of feces by substituting it with puriﬁedintestinal bacterial cultures derived from a singlehealthy donor [24,25]. Additionally, the need tostandardize the protocol for FMT is being recognized[26].Although FMT has been reported mostly in thecontext of recalcitrant CDI, there are emergingapplications of FMT. With the evidence that speciﬁcgut microbes can induce distinct immune responsesin the host and that there is reduced diversity ofthe microbiota in patients with IBD [27-29], it isnot far-fetched to think that restoring a normalmicrobiota will alleviate IBD. Indeed there are eightcases of ulcerative colitis and one case of Crohn’s2disease in which FMT led to remission [30-32].Though not identical to the human disease, there areanimal models that mimic colitis and inﬂammation,which demonstrated that susceptibility to colitis andresistance to enteric infection are transferrable byFMT [33-35].With FMT in IBD still in its infancy, there arelessons to learn from the more widely used FMTfor CDI. First, it is necessary to have controlled andrandomized clinical trials to address the eﬃcacyof FMT in IBD. There are several uncontrolledclinical trials that are ongoing; however, there hasyet to be a study with a control group. Second,a standardized treatment protocol needs to beestablished for stool processing, patient preparation(i.e. antibiotic treatment pre-transplantation), anddelivery method. Lastly, the donor selection andscreening process must be robust and welldocumented. This may be more important fortreatment of IBD than CDI, as multiple infusionsare typically necessary for the former [21], andconsistency between the repeated infusions wouldbe ideal. Current clinical trials will shed light on someof these considerations and will help shape futureinvestigations on the therapeutic value of FMT forIBD.References1. Berg RD: The indigenous gastrointestinal microﬂora. TrendsMicrobiol 1996, 4: 430-4352. Giaﬀer MH, Holdsworth CD, Duerden BI: The assessment of faecalﬂora in patients with inﬂammatory bowel disease by a simpliﬁedbacteriological technique. J Med Microbiol 1991, 35: 238-2433. Gophna U, Sommerfeld K, Gophna S, Doolittle WF, Veldhuyzenvan Zanten SJ: Diﬀerences between tissue-associated intestinalmicroﬂoras of patients with Crohn's disease and ulcerative colitis. JClin Microbiol 2006, 44: 4136-41414. Krook A, Lindström B, Kjellander J, Järnerot G, Bodin L: Relationbetween concentrations of metronidazole and Bacteroides spp infaeces of patients with Crohn's disease and healthy individuals. JClin Pathol 1981, 34: 645-6505. Lepage P, Seksik P, Sutren M, de la Cochetière MF, Jian R,  et al.:Biodiversity of the mucosa-associated microbiota is stable along thedistal digestive tract in healthy individuals and patients with IBD.Inﬂamm Bowel Dis 2005, 11: 473-4806. Mangin I, Bonnet R, Seksik P, Rigottier-Gois L, Sutren M,  et al.:Molecular inventory of faecal microﬂora in patients with Crohn'sdisease. FEMS Microbiol Ecol 2004, 50: 25-367. Manichanh C, Rigottier-Gois L, Bonnaud E, Gloux K, Pelletier E,  et al.:Reduced diversity of faecal microbiota in Crohn's disease revealedby a metagenomic approach. Gut 2006, 55: 205-2118. Van de Merwe JP, Schröder AM, Wensinck F, Hazenberg MP: Theobligate anaerobic faecal ﬂora of patients with Crohn's diseaseand their ﬁrst-degree relatives. Scand J Gastroenterol 1988, 23:1125-11319. Prindiville T, Cantrell M, Wilson KH: Ribosomal DNA sequenceanalysis of mucosa-associated bacteria in Crohn's disease. InﬂammBowel Dis 2004, 10: 824-83310.Scanlan PD, Shanahan F, O'Mahony C, Marchesi JR: Culture-independent analyses of temporal variation of the dominant fecalmicrobiota and targeted bacterial subgroups in Crohn's disease. JClin Microbiol 2006, 44: 3980-398811.Seksik P, Rigottier-Gois L, Gramet G, Sutren M, Pochart P,  et al.:Alterations of the dominant faecal bacterial groups in patients withCrohn's disease of the colon. Gut 2003, 52: 237-24212.Rupnik M, Wilcox MH, Gerding DN: Clostridium diﬃcile infection:new developments in epidemiology and pathogenesis. Nat RevMicrobiol 2009, 7: 526-53613.Musher DM, Aslam S, Logan N, Nallacheru S, Bhaila I,  et al.:Relatively poor outcome after treatment of Clostridium diﬃcilecolitis with metronidazole. Clin Infect Dis 2005, 40: 1586-159014.Zar FA, Bakkanagari SR, Moorthi KM, Davis MB: A comparison ofvancomycin and metronidazole for the treatment of Clostridiumdiﬃcile-associated diarrhea, stratiﬁed by disease severity. ClinInfect Dis 2007, 45: 302-30715.Johnson S: Recurrent Clostridium diﬃcile infection: a review of riskfactors, treatments, and outcomes. J Infect 2009, 58: 403-41016.Crook DW, Walker AS, Kean Y, Weiss K, Cornely OA,  et al.:Fidaxomicin versus vancomycin for Clostridium diﬃcile infection:meta-analysis of pivotal randomized controlled trials. Clin Infect Dis2012, 55 Suppl 2: S93-10317.Louie TJ, Miller MA, Mullane KM, Weiss K, Lentnek A,  et al.:Fidaxomicin versus vancomycin for Clostridium diﬃcile infection. NEngl J Med 2011, 364: 422-43118.Borody TJ, Khoruts A: Fecal microbiota transplantation andemerging applications. Nat Rev Gastroenterol Hepatol 2011, 9:88-9619.Rager KD, George LW, House JK, DePeters EJ: Evaluation of rumentransfaunation after surgical correction of left-sided displacementof the abomasum in cows. J Am Vet Med Assoc 2004, 225: 915-92020.EISEMAN B, SILEN W, BASCOM GS, KAUVAR AJ: Fecal enema asan adjunct in the treatment of pseudomembranous enterocolitis.Surgery 1958, 44: 854-85921.Borody TJ, Campbell J: Fecal microbiota transplantation:techniques, applications, and issues. Gastroenterol Clin North Am2012, 41: 781-80322.Gough E, Shaikh H, Manges AR: Systematic review of intestinalmicrobiota transplantation (fecal bacteriotherapy) for recurrentClostridium diﬃcile infection. Clin Infect Dis 2011, 53: 994-100223.van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG,  et al.:Duodenal infusion of donor feces for recurrent Clostridium diﬃcile.N Engl J Med 2013, 368: 407-41524.Petrof EO, Gloor GB, Vanner SJ, Weese SJ, Carter D,  et al. :Stoolsubstitute transplant therapy for the eradication of Clostridiumdiﬃcile infection: 'RePOOPulating' the gut. Microbiome 2013, 1:325.Tvede M, Rask-Madsen J: Bacteriotherapy for chronic relapsingClostridium diﬃcile diarrhoea in six patients. Lancet 1989, 1:1156-116026.Bakken JS, Borody T, Brandt LJ, Brill JV, Demarco DC,  et al.: TreatingClostridium diﬃcile infection with fecal microbiota transplantation.Clin Gastroenterol Hepatol 2011, 9: 1044-104927.Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T,  et al.: Induction ofintestinal Th17 cells by segmented ﬁlamentous bacteria. Cell 2009,139: 485-49828.Mazmanian SK, Round JL, Kasper DL: A microbial symbiosisfactor prevents intestinal inﬂammatory disease. Nature 2008, 453:620-62529.Qin J, Li R, Raes J, Arumugam M, Burgdorf KS,  et al.: A human gutmicrobial gene catalogue established by metagenomic sequencing.Nature 2010, 464: 59-6530.Bennet JD, Brinkman M: Treatment of ulcerative colitis byimplantation of normal colonic ﬂora. Lancet 1989, 1: 16431.Borody TJ, George L, Andrews P, Brandl S, Noonan S,  et al.:Bowel-ﬂora alteration: a potential cure for inﬂammatory bowel diseaseand irritable bowel syndrome? Med J Aust 1989, 150: 60432.Borody TJ, Warren EF, Leis S, Surace R, Ashman O: Treatment ofulcerative colitis using fecal bacteriotherapy. J Clin Gastroenterol2003, 37: 42-4733.Garrett WS, Lord GM, Punit S, Lugo-Villarino G, Mazmanian SK,  etal.: Communicable ulcerative colitis induced by T-bet deﬁciency inthe innate immune system. Cell 2007, 131: 33-4534.Willing BP, Vacharaksa A, Croxen M, Thanachayanont T, FinlayBB: Altering host resistance to infections through microbialtransplantation. PLoS One 2011, 6: e2698835.Ghosh S, Dai C, Brown K, Rajendiran E, Makarenko S,  et al.:Colonic microbiota alters host susceptibility to infectious colitisby modulating inﬂammation, redox status, and ion transportergene expression. Am J Physiol Gastrointest Liver Physiol 2011, 301:G39-49

Fecal microbiota transplantation as an alternative treatment for infection and inflammation

https://zenodo.org/record/816317/files/bid-1-1-3.pdf

Fecal microbiota transplantation as an alternative treatment for infection and inflammation

Abstract

Similar works

Full text

Available Versions

ZENODO