Editor's Note:
FMT, or Fecal Microbiota Transplantation, offers a novel and promising avenue to manage numerous health conditions, extending beyond the typical use cases of C. diff and IBS. It involves the strategic transfer of fecal matter from a healthy donor to a recipient's gut. While the concept may initially seem unpalatable, the potential health benefits are transformative and compelling.
In his latest article, Art Solbrig illuminates the fascinating journey of FMT – its historical development, varied delivery methodologies, and vast therapeutic potential. This unconventional yet potent procedure significantly influences the gut microbiome, paving the way for notable improvements in health.
by Art Solbrig | July 9, 2023
Fecal Microbiota Transplantation (FMT) is the process of taking fecal matter from a healthy donor who has been screened according to stringent standards, testing the fecal transplant for pathogens, and if found to meet predetermined standards is then implanted in the intestinal tract of a recipient, usually via colonoscopy delivery, who has a health condition such as Clostridium difficile (C. diff) to treat the condition and improve the health status of the recipient.
Although this approach has worked well in C. diff patients who have failed to respond well to standard therapy, it does require rigorous donor and fecal screening to prevent passing on dangerous pathogens or health conditions from the donor to the recipient.
Besides delivery via colonoscopy, as described above, another delivery method besides colonoscopy delivery is via capsules of frozen transplant material. These FMT capsules have shown effectiveness similar to the colonoscopy-delivered FMT in studies, but very importantly, they avoid the potential for problems seen in colonoscopy delivery, such as damage to the colon itself, which is definitely counterproductive. Another advantage of FMT capsules is they are more cost-effective.
There is a third delivery method via the nose to the duodenum, but this method has shown reduced efficacy in some studies when compared to colonoscopy delivery or FMT capsule delivery. It also carries the risk of aspiration, which does not seem worth the risk, when capsules seem to have better efficacy and completely avoid the risk of aspiration.
Lastly, there is a fourth delivery method delivering FMT via enema. In studies to date, the capsule delivery method seems like a good option in terms of safety and ease of use, especially in longer-term use of FMT. Between FMT capsules and enema delivery, the effectiveness seems to vary on a personal level with some recipients achieving a better response to one over the other.
Another very important consideration is the quality of the donor transplant which is thought to be a major cause of significant variability in study results. This problem should be minimalized in time as donor screening parameters are refined significantly and improved.
For some, the whole concept of FMT may be distasteful or unpleasant, but when you consider that you are just manipulating the gut microbiome with a more healthful group of bacteria over the existing not so healthy bacteria, it makes more sense. Consider that when bacteria-free mice were given an FMT from people with Parkinson's disease, the mice got PD-like symptoms. When people with PD were given FMT from healthy human donors, their PD symptoms were significantly reduced. This gives a good indication of what the right and wrong gut bacteria can do for us.
In newer studies, two or three highly potent antibiotics are often used before the administration of FMT in order to essentially kill off the existing microbiome to help allow the FMT to get off to a good strong start and take hold without having to battle with the existing gut microbiome for dominancy. The antibiotics are generally stopped two days prior to the FMT. This procedure allows the FMT to essentially start with a clean slate.
A newer version of FMT is called Washed Microbiota Transplantation (WMT). This "washing process" is considered a safer and more refined form of FMT and is becoming more commonly seen in newer studies. The following article goes into significant detail on how the washing process filters out many potential pathogens from the FMT and can be repeated multiple times to refine the finished FMT product :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093410/
Although FMT has been around for decades, it remains relatively obscure to the general public. The first FMT in humans was done in 1958 and has been done in animals for over 100 years, according to the following article. There is also literature suggesting that FMT was practiced in ancient times :
In more recent years, it has been found that FMT has shown the ability to potentially help other health conditions, and the list of health conditions and diseases that FMT seems to be able to help to varying degrees has grown significantly. In the US, the approved use of FMT is mainly for the treatment of C. diff or severe IBS that has not responded to standard therapy. The US is starting to expand research into other uses for FMT, but the US seems to be limited in this respect.
FMT, when done properly, is proving to have a very good safety profile which is often times very significantly better than prescription medications that are typically used for the health conditions that they are now testing FMT for.
In China, they seem to be on a faster track to actually testing FMT in many health conditions in people. In fact, if the studies are an accurate indication of FMT progress, China is clearly doing the more cutting edge studies in greater number when compared to FMT studies done in the US. Most of these studies are very small in size, but diverse in terms of disease pathologies that they are testing FMT for. Some of the results that have been obtained are quite impressive, but because of the small size of the trials, will require further testing in larger groups in order to justify the use of FMT as a mainstream treatment option for multiple diseases and health conditions.
Some important examples of this are testing of FMT for :
1. Parkinson's Disease
2. Autoimmune Hepatitis
3. ALS
4. Ulcerative Colitis
5. Pneumonia
6. Primary Sclerosing Cholangitis (PSC)
7. Psoriasis and Psoriatic Arthritis
8. Alzheimer's Disease
9. Alcoholic Liver Disease
10. Diabetes Type 2
11. Hepatocellular Carcinoma (HCC)
12. Melanoma
13. Systemic Lupus Erythematosus(SLE)
14. Non-Alcoholic Fatty Liver Disease (NAFLD)
15. Autism Spectrum Disorder (ASD)
16. Crohn's Disease
17. Hepatitis B Virus (HBV)
18. Insulin Resistance
19. Major Depressive Disorder (MDD)
20. Graft Versus Host Disease (GVHD)
21. Treatment Of Multidrug-Resistant Organisms
22. Alcoholism
23. Autoimmune Diseases
24. Cancer
25. Psychiatric Disorders
26. Type 1 Diabetes
27. Multiple Sclerosis (MS)
28. Anxiety
29. Covid-19 / Long Covid
30. Chronic Kidney Disease (CKD)
31. Cardiovascular Disease (CVD)
32. Stroke
33. UTI
34. Systemic Sclerosis
35. Ankylosing Spondylitis
36. Anti-Aging
This is an incomplete list, but to give further perspective on just how many diseases FMT has been tested for, the following review discusses 85 diseases that FMT has been tested for :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9746749/
Here is a relevant quote from this comprehensive review of studies :
' The current review aimed to create an encyclopedia of clinical FMT reports of benefits, including case reports, case series reports, real-world studies, and RCT studies. Since FMT was formally named in 2011, a total of emerging 85 diseases treated by FMT have been reported. The number of studies on FMT/WMT has increased dramatically within the past decade. Integrated with our previous systematic review on FMT-related AEs from 2000 to 2020 worldwide, we profiled the back side and front side of FMT. Although many further controlled trials will be needed, the dramatic increasing in reports has shown the promising future of FMT for dysbiosis-related diseases in the gut or beyond the gut. '
Given the huge potential of uses for FMT, the chances for serendipitous discoveries for new uses for FMT is very high because often, when a person is treated with FMT for one condition, it may turn out to have a positive effect on another health issue that that person may have. As an example of this, in a 2023 FMT study for Parkinson's disease, one patient had complete clearing of psoriasis that had been unresponsive to a highly potent topical steroid and other treatments. Here is a link to that study :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10019775/
Now I would like to discuss a few FMT studies or case reports to give more specific ideas of how FMT can affect various diseases or health conditions. Keep in mind that most FMT studies are small and will require larger randomized, placebo-controlled trials to confirm initial study findings.
It is worth mentioning that seven of the study links used in this article are from China, while two are from the US and one of the US studies was a review of other studies, two studies were from Australia, one study was from the UK, one study was from Iran, one study was from India and one study was from Ukraine.
This systematic review showed that FMT achieved multiple improvements in children with autism spectrum disorder (ASD) and saw significant improvement in autism symptoms in these children :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017995/
This is what the systematic review concluded :
' In conclusion, this review showed that, in the observational and case studies, the FMT showed its potential in reducing the CARS, ABC, and SRS scores and improving ASD symptoms among children with ASD. FMT may be a potential therapy for alleviating symptoms of ASD in children with ASD. However, rigorously designed randomized double-blind placebo-controlled trials are needed to establish the safety and efficacy of FMT as a treatment to ASD. '
This next FMT study was done in ulcerative colitis (UC) patients and found significant benefit for UC patients beyond standard therapy :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9877446/
' Even single transplantation of fecal microbiota (fresh material) bears the potential to be a well-tolerated and safe method of treatment in a large number of patients with mild-to-moderate UC, contributing to an increase in the effectiveness of basic therapy after 4 and 8 weeks, as well as a significant improvement in the abundance of the gut microbiota as early as 4 weeks after FMT. The addition of FMT to the standard therapeutic protocols for UC warrants efficacy at reaching clinical improvement and preservation of gut eubiosis, in line with the goals of precision medicine. '
This next randomized controlled trial (RCT) illustrates that FMT reverses insulin resistance (IR) in people with type 2 diabetes in just four weeks :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9872724/
This RCT reached the following conclusion :
' In conclusion, our study showed that FMT improved the BMI, PBG, HbA1c, FBG, HOMA-HBCI, and HOMA-IR of T2DM patients in 4 weeks and also promoted the engraftment of donor-associated microbiota in participants. Results from our trial will serve as a basis for the long-term intervention of FMT in T2DM patients and the further development of novel biotherapeutic strategies aimed at combatting T2DM through the safe, effective, and affordable bacterial formulations. '
This next pilot randomized controlled trial (RCT) found that FMT delivered via enema for the treatment of Major Depressive Disorder (MDD) met or exceeded all study feasibility targets and was safe :
https://pubmed.ncbi.nlm.nih.gov/36637229/
Here is a relevant quote from the RCT :
' All feasibility targets were met or exceeded. This study found that enema-delivered FMT is feasible, acceptable, well-tolerated, and safe in patients with MDD. '
The following is only an animal study of FMT in an Alzheimer's model that showed that benefit was achieved very quickly in this AD animal model in terms of improvement in cognition as well as pathology:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818266/
Here is a relevant study quote :
' We report significant changes in amyloid plaque burden and cognitive measures in the 5xFAD mouse model of Alzheimer’s disease following a 7-day fecal microbiota transplantation. A complete reversal in cognitive measures in 32-week-old (at commencement of treatment) 5xFAD mice who received FMT from 8–10-week-old (young) wildtype donors and normalization in cognitive measures accompanied by decreases in amyloid plaque load in 32-week-old transgenic mice receiving FMT from age-matched donors suggest a novel treatment strategy for Alzheimer’s disease that is easily translatable to human patients and supports other studies that show that clearing amyloid plaques in the brain is associated with cognitive improvements. We also demonstrate that donor age plays an important role in fecal microbiota transplantation that must be further investigated. '
To add further confirmation to the above AD study, the following systematic review of studies in humans and animals with AD shows that FMT is effective in the treatment of AD :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9637434/
Here is what the systematic review concluded :
' In conclusion, FMT can potentially become one of the modalities in treating AD, exerting its effect through the microbiota-gut-brain axis. The diversity of the gut microbiota in AD patients is widely changed compared with the healthy population as the types of bacteria abundant in healthy people differ from those in AD patients. This is speculated to participate in AD pathophysiology because the original gut bacteria metabolize peptides, soluble fibers, and dietary proteins, bringing out SCFAs and tryptophan along with other metabolites. These products work to lessen gut inflammation along with BBB permeability. Animal studies have demonstrated the FMT effect to restore the SCFAs and a healthy microbiome to disrupt the Aβ oligomers, decreasing AD's pathogenesis. However, the lack of clinical trials due to ethical concerns has hindered our findings in humans. '
' Nevertheless, two case reports were identified in which 82- and 90-year-old patients had received FMT from fit donors and the recipients exhibited cognition improvements. Future recommendations from this review would be to conduct further studies, especially randomized controlled trials, where FMT is implemented in patients of AD at various stages of the disease, following them up for longer durations. Thus, a further detailed assessment of its effect as a possible AD intervention could be evaluated. '
The above study clearly describes the multiple methods of action that FMT utilizes in order to be effective in people with AD.
This next randomized trial shows how FMT in Severe Alcoholic Hepatitis (SAH) increases survival and decreases infections over standard therapy :
https://pubmed.ncbi.nlm.nih.gov/36469298/
Here is an important quote from the trial :
' In severe alcoholic hepatitis, FMT is safe and improves 90-day survival and reduces infections by favorably modulating microbial communities. It can be a useful alternative to prednisolone therapy. '
Autoimmune diseases encompass a large group of diseases that are generally difficult to treat and the following systematic review and meta analysis comprehensively discusses the effectiveness of FMT as a treatment for autoimmune diseases :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9562921/
This systematic review and meta-analysis is, in my opinion, very important, and reached the following conclusions after analyzing multiple studies involving the use of FMT for autoimmune diseases and I find their results quite compelling and very important for people who have these hard-to-treat autoimmune diseases :
' Based on this systematic review and meta-analysis, the application of FMT in the treatment of autoimmune diseases is effective and relatively safe, and it is expected to be used as a method to induce remission of active autoimmune diseases. The transplantation route, source of fecal bacteria, application of antibiotics, and fecal types had no significant effect on the curative effect. Multiple long-term treatments with FMT could improve the curative effect. '
The following is a single case report of a woman with Amyotrophic Lateral Sclerosis (ALS) who was treated with FMT which resulted in disease improvement as well as a stoppage of disease progression. Subsequently, this woman had a trauma to her scalp which required the use of antibiotics. The antibiotics resulted in a worsening of disease symptoms and loss of the symptom relief that had been obtained from the FMT. After the the antibiotic regimen was completed, she was immediately put back on FMT with a resulting improvement of her symptoms and another stoppage of disease progression. There currently are no drugs available for ALS which can stop disease progression or offer significant symptom relief, so this case report is very important and warrants further study in a larger group of people with ALS :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9898040/
Here is an important quote from the case report :
' In conclusion, we for the first time reported the positive clinical outcomes of using WMT for treating ALS. Although the disease condition of the present case was exacerbated by the use of antibiotics, the administered WMTs successfully reversed the worse status of the disease through a long-term follow-up. The current clinical findings would open a new window on the microbiota-based treatment for the life-threatening ALS. '
This next study deals with FMT and Parkinson's disease (PD). In this study, FMT reduced symptom scores by very significant amounts for 3 months which was the study length with just one treatment and also stopped constipation and small intestinal bacterial overgrowth (SIBO), which are both very common health problems in PD.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120701/
Here is a relevant study quote :
' After FMT, the H-Y grade, UPDRS, and NMSS of PD patients decreased significantly. Through the lactulose H2 breath test, the intestinal bacterial overgrowth (SIBO) in PD patients returned to normal. The PAC-QOL score and Wexner constipation score in after-FMT patients decreased significantly. Our study profiles specific characteristics and microbial dysbiosis in the gut of PD patients. FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms. '
This next study shows how FMT reverses Insulin Resistance (IR) in type 2 diabetic patients while also improving diabetes disease parameters in just 4 weeks :
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9872724/
Here is a relevant study quote :
' In conclusion, our study showed that FMT improved the BMI, PBG, HbA1c, FBG, HOMA-HBCI, and HOMA-IR of T2DM patients in 4 weeks and also promoted the engraftment of donor-associated microbiota in participants. Results from our trial will serve as a basis for the long-term intervention of FMT in T2DM patients and the further development of novel biotherapeutic strategies aimed at combatting T2DM through the safe, effective, and affordable bacterial formulations. '
This last systematic review of FMT and stroke shows that FMT is effective and can improve survival rate:
https://pubmed.ncbi.nlm.nih.gov/36162378/
Here is what the systematic review of multiple studies concluded :
' Our systematic review of preclinical studies showed that manipulating gut microbiota via FMT can be a possible therapeutic approach for the treatment of stroke and recovery of post-stroke complications. '
I want to add this last animal study because it shows another interesting aspect of FMT that may also apply to humans, but so far there are no studies to confirm this effect in humans. The following study shows that when you give FMT to older mice from younger mice, the older mice start acting younger, and some of their health parameters are altered more toward the parameters seen in younger mice. Also, when FMT from older mice is transplanted to younger mice, the younger mice take on health parameters seen in older mice :
https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-022-01243-w
Here is an important quote from the study :
' We show that microbiota composition profiles and key species enriched in young or aged mice are successfully transferred by FMT between young and aged mice and that FMT modulates resulting metabolic pathway profiles. The transfer of aged donor microbiota into young mice accelerates age-associated central nervous system (CNS) inflammation, retinal inflammation, and cytokine signaling and promotes loss of key functional protein in the eye, effects which are coincident with increased intestinal barrier permeability. Conversely, these detrimental effects can be reversed by the transfer of young donor microbiota. '
' These findings demonstrate that the aging gut microbiota drives detrimental changes in the gut–brain and gut–retina axes suggesting that microbial modulation may be of therapeutic benefit in preventing inflammation-related tissue decline in later life. '
So the information and studies above illustrate the broad-ranging health effects of FMT, and future studies will only further broaden the potential health range of FMT. Given the newer standards for screening donors and fecal transplants as well as the newer WMT version, the safety profile of FMT is very good and improving and better than most drugs used to treat the diseases that FMT is being used for around the world.
One downside to FMT is availability since, in the US, it is mainly approved for C. diff and IBS-d, which has failed under a standard of care treatment. Increased ease of use and lower cost via FMT capsules make it a non-invasive approach to potentially treating many diseases and health issues. Larger studies will help to establish FMT as a mainstream viable treatment option. FMT also shows the ability to do more than some current treatments for the diseases it is being used for. While drugs are often designed to treat one specific disease or its symptoms, FMT offers the potential to treat multiple diseases or health issues at the same time in each individual.
FMT is clearly showing how important the gut microbiome is to our health on multiple levels and how manipulating the gut microbiome through FMT can greatly improve our health! It can also help drive healthcare costs down and significantly reduce the side effects of prescription medications.
Art
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