Key messages
• Ulcerative colitis (UC) and Crohn disease (CD) are two forms of inflammatory bowel disease (IBD). IBD is an autoimmune disease affecting the gut, as the body's immune system mistakenly attacks healthy cells, tissues, and organs.
• Fecal transplantation may increase the proportion of people with active UC who achieve control of the disease, defined as clinical remission (disease control defined based on clinical symptoms) and endoscopic remission (disease control defined based on endoscopic findings), and may have little to no effect on rates of any adverse events (unwanted events that causes harm to the person).
• The evidence was very uncertain about the risk of serious adverse events and improvement in quality of life when fecal transplantation was used for control of active UC.
• The evidence was also very uncertain about the use of fecal transplantation for induction of remission in people with active CD and maintenance of remission in people with UC or CD.
• Fecal transplantation is an evolving therapy and further studies are needed to evaluate its benefits and risks in both adults and children with active UC or CD, as well as its potential use for long-term control of UC and CD.
What is inflammatory bowel disease?
UC and CD are two forms of IBD that can cause weight loss, abdominal pain, and blood loss due to inflammation (pain and swelling) in the gastrointestinal (GI) tract, affecting an estimated 6.8 million people worldwide. The exact reasons that people develop IBD are still to be determined, but are thought to involve a complex interaction between the immune system, the GI tract lining, the environment, and the gut microbiome, leading to an abnormal inflammatory response in genetically susceptible individuals. Evidence suggests that an unhealthy composition of the gut microbiota is associated with development of IBD, and its correction may help to control the inflammation seen in IBD. Stool administration from healthy donor to patient, called fecal microbiota transplantation (FMT), may restore a healthy balance of gut microbiota and control IBD-related inflammation both in active disease (called induction of remission) and on a long-term scale (called maintenance of remission).
What did we want to assess?
We wanted to assess the benefits and risks of FMT for treatment of IBD (UC and CD).
What did we do?
We searched multiple databases for randomized controlled trials (RCTs), a study design considered to be superior for assessment of clinical interventions, that compared FMT to control therapies for IBD. We combined the data from multiple studies when possible and rated our confidence in the evidence based on factors such as study methods, participants' awareness of the treatment they received, and sample sizes.
What did we find?
Ten studies (nine in adults and one in children) showed that FMT may increase rates of induction of clinical remission and endoscopic remission and may result in little to no difference in rates of any adverse events in people with active UC. The data on risk of serious adverse events and improvement in quality of life were very uncertain, and no conclusions could be drawn regarding these outcomes.
Two studies reported data on use of FMT for maintenance of remission in adults with controlled UC. Overall, the evidence was very uncertain about the use of FMT to maintain clinical or endoscopic remission in controlled UC, as well as the associated risk of adverse events and improvement in quality of life.
None of the included studies reported data on use of FMT for control of active CD.
One study reported data on use of FMT for maintenance of remission in adults with controlled CD, and the evidence was very uncertain about the benefits and risks of FMT when used to maintain clinical remission in controlled CD.
The studies varied in their methods, dosages, and frequencies of FMT administration, as well as the types of donors and baseline severity of disease. The FMT administration methods included oral capsule, nasoduodenal tube (a tube that travels from the nose to small bowel via the stomach), rectal enema, colonoscopy (a tube inserted into the colon via the anus), and combinations of these methods.
What are the limitations of the evidence?
Our confidence in the evidence was limited due to the small numbers of participants, concerns regarding how the studies were conducted, and variations of effect among studies in some of the analyses. Additional studies are needed to address the benefits and risks of FMT in adults and children with IBD.
How up-to-date is this evidence?
This review is an update of our previous review that was published in 2018. The evidence is up-to-date as of 22 December 2022.
FMT may increase the proportion of people with active UC who achieve clinical and endoscopic remission. The evidence was very uncertain about whether use of FMT in people with active UC impacted the risk of serious adverse events or improvement in quality of life. The evidence was also very uncertain about the use of FMT for maintenance of remission in people with UC, as well as induction and maintenance of remission in people with CD, and no conclusive statements could be made in this regard. Further studies are needed to address the beneficial effects and safety profile of FMT in adults and children with active UC and CD, as well as its potential to promote longer-term maintenance of remission in UC and CD.
Inflammatory bowel disease (IBD) is a chronic, relapsing disease of the gastrointestinal (GI) tract that is thought to be associated with a complex interplay between the immune system, the GI tract lining, the environment, and the gut microbiome, leading to an abnormal inflammatory response in genetically susceptible individuals. An altered composition of the gut's native microbiota, known as dysbiosis, may have a major role in the pathogenesis of ulcerative colitis (UC) and Crohn disease (CD), two subtypes of IBD. There is growing interest in the correction of this underlying dysbiosis using fecal microbiota transplantation (FMT).
To evaluate the benefits and safety profile of FMT for treatment of IBD in adults and children versus autologous FMT, placebo, standard medication, or no intervention.
We searched CENTRAL, MEDLINE, Embase, two clinical trial registries, and the reference sections of published trials through 22 December 2022.
We included randomized controlled trials that studied adults and children with UC or CD. Eligible intervention arms used FMT, defined as the delivery of healthy donor stool containing gut microbiota to a recipient's GI tract, to treat UC or CD.
Two review authors independently screened studies for inclusion. Our primary outcomes were: 1. induction of clinical remission, 2. maintenance of clinical remission, and 3. serious adverse events. Our secondary outcomes were: 4. any adverse events, 5. endoscopic remission, 6. quality of life, 7. clinical response, 8. endoscopic response, 9. withdrawals, 10. inflammatory markers, and 11. microbiome outcomes. We used the GRADE approach to assess the certainty of evidence.
We included 12 studies with 550 participants. Three studies were conducted in Australia; two in Canada; and one in each of the following: China, the Czech Republic, France, India, the Netherlands, and the USA. One study was conducted in both Israel and Italy. FMT was administered in the form of capsules or suspensions and delivered by mouth, nasoduodenal tube, enema, or colonoscopy. One study delivered FMT by both oral capsules and colonoscopy. Six studies were at overall low risk of bias, while the others had either unclear or high risk of bias.
Ten studies with 468 participants, of which nine studies focused on adults and one focused on children, reported induction of clinical remission in people with UC at longest follow-up (range 6 to 12 weeks) and showed that FMT may increase rates of induction of clinical remission in UC compared to control (risk ratio (RR) 1.79, 95% confidence interval (CI) 1.13 to 2.84; low-certainty evidence). Five studies showed that FMT may increase rates of induction of endoscopic remission in UC at longest follow-up (range 8 to 12 weeks); however, the CIs around the summary estimate were wide and included a possible null effect (RR 1.45, 95% CI 0.64 to 3.29; low-certainty evidence). Nine studies with 417 participants showed that FMT may result in little to no difference in rates of any adverse events (RR 0.99, 95% CI 0.85 to 1.16; low-certainty evidence). The evidence was very uncertain about the risk of serious adverse events (RR 1.77, 95% CI 0.88 to 3.55; very low-certainty evidence) and improvement in quality of life (mean difference (MD) 15.34, 95% CI −3.84 to 34.52; very low-certainty evidence) when FMT was used to induce remission in UC.
Two studies, of which one also contributed data for induction of remission in active UC, assessed maintenance of remission in people with controlled UC at longest follow-up (range 48 to 56 weeks). The evidence was very uncertain about the use of FMT for maintenance of clinical remission (RR 2.97, 95% CI 0.26 to 34.42; very low-certainty evidence) and endoscopic remission (RR 3.28, 95% CI 0.73 to 14.74; very low-certainty evidence). The evidence was also very uncertain about the risk of serious adverse events, risk of any adverse events, and improvement in quality of life when FMT was used to maintain remission in UC.
None of the included studies assessed use of FMT for induction of remission in people with CD.
One study with 21 participants reported data on FMT for maintenance of remission in people with CD. The evidence was very uncertain about the use of FMT for maintenance of clinical remission in CD at 24 weeks (RR 1.21, 95% CI 0.36 to 4.14; very low-certainty evidence). The evidence was also very uncertain about the risk of serious or any adverse events when FMT was used to maintain remission in CD. None of the studies reported data on use of FMT for maintenance of endoscopic remission or improvement in quality of life in people with CD.