Fecal microbiota transplantation: The When,the How and the Don t By Dr Rola Hussein
Introduction Fecal microbiota transplantation (FMT) involves administration of fecal material containing distal gut microbiota from a healthy donor to a patient with a disease related to dysbiosis or an alteration in gut microbiota.
The gastrointestinal tract contains > 100 trillion bacteria of > 1000 species. 1 The gut microbiota affect metabolism, nutrition and the immune system This balanced homeostasis between the host and gut microbiota is called symbiosis. 2 1. Blaser M, Bork P, Fraser C, Knight R, Wang J.Nat Rev Microbiol 2013 2. Round JL, Mazmanian SK. Nat Rev Immunol 2009
Technique
Donor selection Donors are usually selected from relatives, spouses, friends, or healthy volunteers 1. Relatives or spouses: Low risk of transmission of infectious agents (share some infectious risk factors) 2. Healthy volunteers: Alter the recipient s gut microbiota most significantly because they do not share a genetic or environmental background with the recipient.
Done if the receipient is immunocompromised or in cases Minimal of potential donor recommended exposures. testing
Preparation of fecal materials This processed specimen is either directly infused into the GI tract, frozen or placed into gelatin capsules (stool bank)
Bottles of frozen stool Bottles of frozen human stool for fecal transplants at the nation's first stool bank, OpenBiome
Routes of administration Include: Nasogastric tube EGD Colonoscopy Rectal enema
A systematic literature review of FMT treatment for recurrent CDI and pseudomembranous colitis. 317 patients from 27 case series and reports FMT was highly effective, showing disease resolution in 92% of cases.
A metanalysis of 18 studies: 9 cohort studies, 8 case studies and 1 RCT 122 patients were described (79 ulcerative colitis (UC); 39 Crohn's disease (CD); 4 IBD unclassified). Overall, 45% (54/119) of patients achieved CR during follow-up.
Among the cohort studies, the pooled proportion of patients that achieved CR was 36.2% (95% CI 17.4%
Subgroup analyses demonstrated a pooled estimate of clinical remission of 22% (95% CI 10.4 40.8%) for UC (P
Subgroup analyses demonstrated a pooled estimate of clinical remission of 60.5% (95% CI 28.4% 85.6%) for CD (P = 0.05; I2 =
IBS Several studies have found alterations in the gut microbiome in patients with IBS. 1,2 Recent studies suggest that changes in the gut microbiota may be responsible for underlying mechanisms associated with IBS such as visceral hypersensitivity, altered barrier function, GI motility, and the gut-brain axis. 3,4 1. Malinen E, Rinttila T, Kajander K, et al. Am J Gastroenterol 2005 2. Simren M, Barbara G, Flint HJ, et al. Gut 2013Crouzet L, Gaultier E, Del Homme C, et al. 2013 3. Kashyap PC, Marcobal A, Ursell LK, et al.. Gastroenterology 2013.
So gut microbiota is an important target for study in the treatment of functional disorders such as IBS..Use of prebiotics and probiotics, dietary restrictions, and antibiotics to modulate the gut microbiota.
atio obe in Visceral hypersensitiv ity Abnormal gut motility Autonomic nervous system dysfunction Immune dysfunction Psy Karantanos et al., 2010 Bischoff, 2009 Chadwick et al., 2002 Cremon et al., 2009
Factors supporting use of FMT in IBS: Postinfection IBS occurs in 10-30% of patients after acute gastroenteritis.6-7-fold increase in the development of IBS.(Spiller and lam, 2012) Studies have shown that the composition of the microbiota in IBS patients is different from that of healthy controls (simren et al., 2013) IBS symptoms can be improved antibiotics, probiotics and prebiotics (kajander et al., 2008; sachdev and pimentel, 2012; spiller, 2008).
Fecal microbiota transplantation in diarrhea-ibs Pinn et al. reported on 8 patients with refractory IBS-D 80% 60% 40% 70% 72% 69% 67% Limitations: small number of 50% patients for a very common 46% 42% disorder 20% 0% Resolution of symptoms Bowel habits bloating quality of life Pinn DM, Aroniadis OC, Brandt LJ. [abstract]. ACG 2013 Annual Scientific Meeting and Postgraduate Course; 11 16 October 2013. San Diego, CA: San Diego Convention Center.
Constipation-IBS Significantly lower levels of butyrate producing bacteria Chassard C, Dapoigny M, Scott KP, et al. Aliment Pharmacol Ther 2012
Function of butyrate: antiinflammatory effects, colonic defence barrier and decrease in oxidative stress
H2S cause: 1. Visceral pain-like nociceptive behaviour in mice..h2s. 1 2. Inhibit in vitro motor patterns in human and rodent colon. 2 1. Zupancic ML, Cantarel BL, Liu Z, et al. PLoS One 2012 2. Borody TJ, Campbell J, Torres M, et al. Am J Gastroenterol 2011
C-IBS patients have higher levels of sulphate reducing bacteria leading to increased H2 production.. gas-related symptoms, i.e. bloating and flatus. 1 1. Borody TJ, Campbell J, Torres M, et al. Am J Gastroenterol 2011
A case series of 45 patients with IBS-C who were treated with transcolonoscopic FMT followed by FMT enema infusions of 17 cultured GiMb components. 40/45 patients 90% 89% 68% 18/30 patients 60% 45% 23% 0% Relief in defecation, bloating and abdominal pain Immediately after the procedure Andrews P, Borody TJ, Shortis NP, Thompson S. Gastroenterology 1995
A case series of 55 patients who underwent FMT treatment for IBS and IBD 50% 47% 38% 36% 25% 16% 13% 0% cure Symptom relief No response Unfortunately, no distinction within results was made between the two diseases Borody TJ, George L, Andrews PJ. Med J Aust 1989.
45 studies were included: 34 on Clostridium difficile -infection (CDI) 7 on inflammatory bowel disease 1 on metabolic syndrome 1 on constipation 1 on pouchitis 1 on irritable bowel syndrome (IBS)
Disease Number of patients response CDI 867 90% UC 106 0% to 68% CD 6 no benefit IBS 13 70% Constipation 3 100% Pouchitis 8 No benefit Insulin sensitivity 10 significant improvement
Limitations: Studies of FMT in IBS are rare Small number of patients Selection bias (case series or reports Many unanswered questions ( patient selection, donor selection, frequency of administration) The alteration of gut microbiota was temporary in most patients.. necessity of periodically repeated transplantation to maintain the altered gut microbiota.
Short-term Adverse Events 1. Minor events: Abdominal discomfort, bloating, flatulence, diarrhea, constipation, borborygmus, vomiting, and transient fever. 2. Serious events: Complications of endoscopy (perforation and bleeding) Sedation Transmission of enteric pathogens appears to be rare with current screening.(limited to case reports). 1 1.Quera R, Espinoza R, Estay C, et al. J Crohns Colitis 2014
Aspiration Progressive pneumonia
Potential Long-term Adverse Events 1. The theoretical possibility of transmission of unrecognized infectious agents that cause illness years later 2. Development of diseases related to changes in the gut microbiota (obesity, diabetes, atherosclerosis, IBD, colon cancer, NAFLD, IBS, asthma, and autism)
Contraindications FMT is generally considered to be relatively contraindicated in patients with severe comorbid conditions, or those taking immunosuppressants, although anecdotally, such patients have been successfully treated.
Conclusion FMT is very exciting and is likely to change the way physicians think about functional bowel disorders However safety must remain a concern Randomized controlled trials must be performed to establish efficacy and safety.
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