“FMT differs from other IBD therapeutics as the intended outcome for treatment is to ultimately cure IBD.”
Everyone has heard of kidney, heart, or other organ transplantations but many people may be surprised to discover that transplanting intestinal microbes is emerging as a promising new treatment option for several gastrointestinal, metabolic, and neurological disorders. Microbes in the intestinal tract, or the gut microbiota, play a pivotal role in both metabolic and immune function. Although everyone has a unique composition of microbes in the intestines, a healthy gut is highlighted by microbial diversity and stability. An imbalance in the composition of bacterial species in the gut is associated with the pathogenesis of many disorders, such as inflammatory bowel disease (IBD).
Fecal microbiota transplantation (FMT) is designed to restore this balance by replenishing the gut with bacteria isolated from the feces of healthy donors. Fecal samples contain billions of live bacteria that originate directly from the gut and can be administered to recipients either through direct intestinal infusions or through oral capsules. There are other treatment options that can influence the gut microbiota, such as prebiotics or probiotics, however, these methods only support the growth of specific species of bacteria. FMT is advantageous since it can provide a wide variety of bacterial species spanning the entire ecosystem of a healthy individual’s gut microbiota. FMT has been demonstrated to successfully cure 90% of people who have a recurrent infection from a bacterium, Clostridioides difficile. FMT is now emerging as an exciting potential treatment option for IBD.
IBD is a heterogeneous group of disorders (including Crohn’s disease and ulcerative colitis) characterized by chronic inflammation along the intestinal tract and is suggested to be caused by a combination of genetic and environmental factors that leads to an inappropriate immune response to the gut microbiota. Conventional IBD treatment options, primarily anti-inflammatory and immunosuppressive drugs, have been designed to alleviate symptoms, prevent further complications, and restore damage to the intestinal mucosal layer. Although there are many medication options available, there is still a serious proportion of individuals with IBD who fail to respond or lose their response to medication. Adverse reactions to medication can also occur in some patients, especially in those who have other comorbidities. In Canada, approximately $1.28 billion is spent annually on IBD care as Canadians experience one of the highest rates of IBD.
FMT differs from other IBD therapeutics as the intended outcome for treatment is to ultimately cure IBD. Currently, the effectiveness of FMT for IBD treatment remains unclear. There has only been a limited number of controlled clinical trials testing FMT treatment for IBD. Although the results of these studies have been conflicting and treatment outcomes have not been as remarkable as for treating C. difficile, several groups have identified that more patients have undergone clinical remission after FMT compared to the placebo. Notably, in one study, remission success rates were higher in IBD patients who had a greater enrichment of the transplanted bacteria.
FMT donor selection is determined by donor health, age, BMI, and fecal weight. Although FMT doesn’t require specifically matched donors like organ transplantation, identifying donor samples with particular bacterial species compositions may be beneficial. For example, higher concentrations of E. hallii and R. inulivorans following FMT have been associated with greater remission outcomes. Additionally, a decline in members of Lachnospiraceae family and the Bacteroidetes phylum can be seen in the IBD microbiota in the absence of FMT treatment. Moreover, the heterogeneity of IBD suggests that a personalized approached may be necessary to fully capture the potential of FMT for IBD treatment.
FMT incorporating fecal samples from multiple donors is another way that can potentially amplify FMT effectiveness. It was recently demonstrated that FMT using fecal microbes from multiple donors increased bacterial diversity in IBD patients and improved patient outcomes compared to FMT that used a singular donor per recipient. Another option that can potentially improve the success rate of FMT is to administer antibiotics and deplete some residents of the gut microbiota prior to transplantation. The combination of antibiotics and FMT has been identified to improve remission rates, however, the process of determining which antibiotics to use has yet to be standardized. FMT optimization is still in its infancy and potentially incorporating donor personalization, multiple donor selection, and antibiotic use makes FMT an attractive therapy for further development.
While in the short-term FMT appears to be relatively safe, the long-term safety of FMT has yet to be fully evaluated and some long-term adverse events have been reported, including depression (2%), arthritis (7%), and allergic bronchitis (2%). Despite the uncertainty surrounding the safety and effectiveness of FMT, approximately 20% of ulcerative colitis patients and 80% of patients with Crohn’s disease will require intestinal surgery in their lifetime which should be considered when evaluating the potential benefits of FMT.
Ultimately, FMT appears to be a promising treatment option for IBD, although we still need a better understanding of the causes and mechanisms behind the pathogenesis of IBD to harness the full potential of FMT treatment for IBD. It will be interesting to see whether FMT will become the primary treatment option for IBD in the next decade or if the excitement will eventually diminish.
References
1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351938/
2. https://www.frontiersin.org/articles/10.3389/fendo.2021.667066/full
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789542/
4. https://theconversation.com/your-poo-is-mostly-alive-heres-whats-in-it-102848#:~:text=It’s%20estimated%20there%20are%20nearly,of%20the%20bacteria%20were%20alive.
5. https://www.frontiersin.org/articles/10.3389/fphar.2020.574533/full
6. https://www.frontiersin.org/articles/10.3389/fmed.2021.765474/full
7. https://crohnsandcolitis.ca/About-Us/Resources-Publications/Impact-of-IBD-Report8.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646133/
Daniel Zangrando
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