A to Z on FMT: A Lesson on Fecal Microbiota Transplantation

11 min read


You may have heard of fecal microbiota transplantation, or FMT. Research on this technique is popping up everywhere, as are questions about its use. It seems that patients all over the globe, for a variety of health conditions, are wondering how it works, and more importantly, if it can work for them. Whether you’re familiar or unfamiliar with FMT, it’s worth discussing some of the science behind it.


The basics of FMT


Fecal microbiota transplantation works a lot like how it sounds. Essentially, a healthy donor provides a stool sample that is transplanted into the gastrointestinal (GI) tract of another individual. This method can improve the composition and diversity of the recipient’s gut microbiota to help them recover from an illness. An example of a common and encouraging use of FMT is in the case of a recurrent C. difficile infection. C. difficile is an invasive bacterium that likes to reproduce in the intestines and release toxins, leading to severe diarrhea, inflammation, and fever. While C. difficile infection is often successfully treated with antibiotics, in some cases the infection reemerges and the bacteria can become resistant to antibiotics, leaving these patients without many options. At this stage, FMT helps restore the gut microbiota affected by the infection.


While C. difficile infection recovery may be one of the more common reasons to employ FMT, it’s certainly not the first time something like this has been done. The first trace of fecal matter being used as treatment was in China in the 4th century, when it was utilized to improve the condition of patients with severe diarrhea.


Today, there are many more ways to use FMT as a therapy--and not just for infectious diseases. From conditions like obesity to cancer, scientists think they’re just scratching the surface of the potential of FMT. Of most interest to us are the possibilities for inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). But before we get into the specifics of FMT for IBD and IBS, let’s break down the actual process of a fecal microbiota transplantation. (1)


Screening


Unsurprisingly, both donors and patient recipients are screened before FMT is conducted. Around four weeks before donating fecal matter, healthy donor candidates will get blood and stool tests to verify their eligibility. The ideal candidate is 18-65 years of age without a gastrointestinal disease or symptoms of one and has no significant medical comorbidities that could compromise the efficacy of the transplantation. They should also not be on any medications that could affect the quality of their stool, such as antibiotics and probiotics, in the three months before FMT.


Although there hasn’t been strong evidence to establish a relationship between the donor and the outcome of FMT, there are some things to consider when selecting an appropriate donor. For instance, it’s been suggested that people who live together, such as spouses or close relatives, may make the best FMT matches. This is because many environmental risk factors are shared by people living in the same space (think diet, cleaning habits, etc.). For spouses, this could mean reducing the risk of infection transmission, and for close relatives, the immune system may react less to the introduction of microbiota from a donor with similar species present in their feces, which also lessens risks of poor FMT outcomes. However, these are just some theories, and it remains to be seen which type of donor works best for each disease or intended outcome of FMT. (1)


A visual representation of the FMT process (1)


Preparation


After the donor has been selected, there are a few things to be mindful of. Education and support are two important aspects of a successful FMT. Recipients must be prepared and well-informed about the procedure.


From the donor, fecal matter from a stool sample will be thoroughly mixed with a sterile saline solution. This fecal matter contains loads of the beneficial bacteria and other microorganisms that patients need to normalize their disease state. Everything is then filtered to get rid of any large particles. What’s left, called the filtrate, is then either prepared into capsules to be consumed orally or infused into syringes to be introduced into the GI tract of the patient recipient.


If not receiving the filtrate of stool through the capsules, then it’s through endoscopy of the upper or lower GI tract, or another method that allows a physician to target a region of the tract using a tube device. Importantly, patients must avoid antibiotics within the 12-48 hours prior to their FMT. Preparing for the procedure is much like preparing for a colonoscopy; the bowel should be essentially empty such that the donor sample can integrate into its new host in a healthy way, known as engraftment. From there, an endoscopy can be performed to infuse the fecal matter filtrate into the recipient. This is either a colonoscopy or retention enema.


You may be wondering if FMT is a one-time thing or a treatment that requires a collection of doses to work best, but there’s no definitive answer to that question just yet. It all depends on the patient’s condition. A patient’s medical team may closely evaluate their response to FMT in order to assess its efficacy and determine if more instalments of FMT would improve their response.


Now that we all understand the FMT process better, let’s consider how this approach could help people with IBD or IBS. (1)


Fecal Microbiota Transplantation for IBD


It’s well known that the microbiota of someone with inflammatory bowel disease (IBD) is abnormal, and that this imbalance likely contributes to disease activity. With a change in the populations of microorganisms related to good health, many people with IBD could certainly benefit from a healthier gut microbiota. This makes the study of FMT for IBD patients quite an interesting approach. The use of FMT in this way began around 2012, and since then, several studies have investigated its efficacy.


For ulcerative colitis (UC), FMT has been employed in multiple clinical trials. Four trials between 2015 and 2019 determined that in those who had UC for strictly less than a year, FMT could instigate remission, which is the goal for all IBD patients. In another study, the ability to maintain clinical remission (when symptoms are virtually absent over time) was evaluated. Many (87%) of the UC patients in this state of remission maintained remission when reevaluated 48 weeks after their FMT, whereas among those who got the placebo in this trial, only about 67% maintained clinical remission (2). While these results are encouraging, researchers have to keep digging to further investigate how this approach works for people with disease activity (i.e. not in remission), for people with long-term UC, those with other health conditions, and so on. Meanwhile, other studies have pointed to a lack of benefit of FMT for treating UC. For example, people with mild or moderate UC activity were tested for the efficacy of FMT, and there were no notable differences between FMT and a control treatment, indicating that in this case, FMT didn’t have enough of a positive effect (3). The degree of improvement experienced after FMT likely depends on the composition of a donor’s stool, how early the UC is treated, and if multiple FMTs are used (4). With all these different results, there’s still lots to work out when it comes to FMT in UC patients, but it’s quite encouraging to see that it has already helped people.


In terms of Crohn’s disease (CD), there are also mixed results for the effectiveness of FMT. An interesting result from one study that failed to demonstrate any significant benefit of FMT for relieving disease activity in CD patients actually showed that it led to improved health-related quality of life among these participants because of better disease management and attitudes towards FMT after trying it. Since quality of life is (unsurprisingly) such a critical aspect of well-being for CD patients, this can still be considered a notable result (5). Furthermore, there are many case reports on a small sample of CD patients experiencing significant improvements in symptoms due to FMT. For example, one case of severe, refractory (unresponsive to treatment) CD was successfully treated with FMT, contributing to more intrigue in the scientific community to study how remodeling the gut microbiota could be used to heal people from disease (6). In a bigger study, 30 patients with refractory CD were tested and the researchers found some interesting results. After a single round of FMT, the patients had a higher healthy body weight on average, and the treatment had “a fast and continuous significant effect in relieving sustaining abdominal pain associated with sustaining CD” (7). This is an encouraging example of the potential of FMT as a safe and practical treatment to efficiently provide relief to patients with refractory CD. Again, more research is needed to validate this approach in a clinical setting.


You also may be wondering if this treatment could be used on children. There are studies on the use of FMT for pediatric inflammatory bowel disease. In a 2016 study, nine young patients with mild to moderate CD symptoms received FMT through the upper GI tract had improved disease activity and seven of the nine participants achieved remission within 2 weeks of their therapy. The FMT was deemed unsuccessful for those who either didn’t engraft, meaning the transplant didn’t quite succeed, or whose microbiome was more similar to that of their donor, in which cases there was little to no improvement in the patients’ disease (8). This is just one case to demonstrate potential for FMT in pediatric CD, and contributes to a larger discussion about how the donor’s gut microbiota composition can influence recipient patient outcomes.


In general, while FMT for C. difficile infection is known to be a safe, reliable option, the evidence for inflammatory bowel disease is still evolving, and there are reports of worse side effects among these patients after FMT compared to C. difficile patients. In fact, treating C. difficile infection with FMT when patients have an underlying case of IBD has been studied, and it seems that the presence of an IBD contributed to more side effects. Research generally suggests that it’s more likely to have side effects when using FMT to treat IBD versus C. difficile infection, although the side effects experienced tend to be mild or moderate, such as fever. (9)


Fecal Microbiota Transplantation for IBS


Much like for IBD, the evidence for the efficacy of FMT for people with irritable bowel syndrome (IBS) is still growing. An intriguing result from 2019 argued that FMT works against IBS. They tested 165 people with IBS, randomizing who received a placebo (which, if you’re wondering was a fecal transplant of their own stool), a low dose of FMT, or a higher dose of FMT; all the stool used to prepare the treatment was from the same healthy donor. Three months after the therapy, significant improvements in IBS symptoms were achieved in 24% of patients who got the placebo, 77% who got low-dose FMT, and 89% of those who got high-dose FMT, plus significantly better quality of life and less fatigue was exhibited among those who received FMT. When paired with the fact that these recipients also had major changes in their gut microbiota profiles (composition, stability, diversity), there is certainly something to be said about ensuring a healthy donor with a desirable gut microbiota is sampled from, and that higher doses are used (10). As a follow-up to this study, the researchers looked at the impact of FMT for IBS after a year, and found that most of the participants still had a positive response at this point, including improved relief from symptoms and better quality of life. Further, patients’ gut microbiota profiles changed even more for the better compared to the three-month mark (11).


Parting Thoughts


This is certainly an area of ongoing research, but early signs of the efficacy of FMT for these conditions are encouraging. There are many factors that have to be considered to explain why some research fails while others show positive results. The origin of the donor stool, the dosage of the stool, the frequency of the dosage, the nature of the recipient's illness, the recipient's medication protocol and many more factors can impact trial results. For example, FMT will be received differently by a patient who had taken antibiotics prior to the FMT. Therefore, there is no clear answer whether FMT as a standalone treatment can help chronic illness such as IBD or IBS. Another concern with FMT is lack of availability and regulation across countries, leading many to seek out treatment on their own, but it’s important to remember that this is no minor procedure so consulting your healthcare professional is always recommended. While we await more research to expand the availability of FMT, continue to ask your doctors questions about this approach. It never hurts to know more about treatment options and where the medical field stands on these approaches!


Although FMT may not be an option for everyone at the moment, the Phyla microbiome test kit and digital health app certainly are. Not only will this help you become more educated on your health, but it will provide you with key insights into your gut bacteria and what you can do to improve your intestinal health. Download the app on iOS or Android and order a microbiome test kit today!


Sources

1 https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S0929664618305552?returnurl=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0929664618305552%3Fshowall%3Dtrue&referrer=https:%2F%2Fpubmed.ncbi.nlm.nih.gov%2F

2 https://www.ncbi.nlm.nih.gov/pubmed/30873549/

3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530266/#B43

4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5479396/

5 https://www.ncbi.nlm.nih.gov/pubmed/26146498/

6 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819561/

7 https://pubmed.ncbi.nlm.nih.gov/25168749/

8 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4329080/

9 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5479396/

10 https://pubmed.ncbi.nlm.nih.gov/31852769/

11 https://onlinelibrary.wiley.com/doi/10.1111/nmo.14200