Fecal Microbiota Transplant-FMT: The Future Of Medicine

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Learn how fecal microbial transplantation (FMT) works, which conditions it is used for, how it can help with gut issues and how to go about getting one done.

Fecal microbiota transplant (FMT) is the process of transplanting fecal bacteria from a healthy donor to a patient in order to restore the patient’s gut microbiota. The human gut microbiota is the collection of bacteria that live in the entire gastrointestinal tract from the mouth to the anus. However the majority of the gut bacteria reside in the intestines and play significant roles in digestion, production of metabolites and tuning the immune system.

A fecal microbiota transplant usual involves delivering healthy donor stool from a person without disease (stool donors) and presumed to have a healthy gut microbiota via one of the following methods:

  • Colonoscopy
  • Fecal enema
  • Nasogastric tube
  • Capsule (popularly called “poop pills”)

Fecal microbiota transplantation is typically used in patients with various debilitating diseases such as:

  • Clostridium difficile colitis, 
  • Inflammatory bowel diseases (IBD): Ulcerative Colitis or Crohn’s disease
  • Irritable bowel syndrome (IBS)

Function of the human gut microbiome

As stated above, a person’s gut microbiome plays an important role in the health of the individual. It hasn’t been until recently that modern technology has allowed scientists to really begin to understand the purpose of the microbiome within the human body. One of the most important discoveries is the concept that bacterial diversity impacts human health (Khanna et al, 2014).

With this in mind, a microbial imbalance has been associated with a broad spectrum of pathologies ranging from:

There are many potential causes for disruption in the microbial ecosystem of the digestive tract including:

  • Antibiotic overuse
  • Increased consumption of high fat diets
  • Systemic chronic inflammation
  • Organic pollutants
  • Food borne toxins
  • Preservatives
  • Sanitation-related chemicals commonly used in agriculture
  • Lack of fiber in diets

The gut microbiota, in health, live in harmony with the human host and support one another through various means that cannot be otherwise achieved individually.

The commensal bacteria in the microbiome have the task of helping the human host maintain health, or homeostasis through metabolic processes like carbohydrate fermentation and Short Chain Fatty Acid (SCFA) production (Leustean et al, 2018).

In exchange, the host (which is us) offers an environment for which the microbiota can thrive and a wide range of nutrients, like complex carbohydrates that are essential for the microbiota survival. Many of the nutrients that the microbiota are diet derived indigestible fibers and sugars (Woting et al, 2016) such as;

  • cellulose,
  • inulin,
  • xylin,
  • pectin,
  • beta-glucan
  • Fructooligosaccharides (FOS)
  • galacto-oligosaccharides

All of these prebiotics are derived from plant matter and for which humans lack the required digestive enzymes necessary for their absorption by the human host (Han et al, 2014).

This mutualism between humans and the microbiome in the gut is of major importance to both the host and the bacteria. There are significant advantages humans experience when the microbiome is working well including bacteria-specific metabolic reactions such as:

  • Carbohydrate fermentation
  • Vitamin K.
  • Production of Short Chain Fatty Acids (SCFA)
  • Bile dihydroxylation
  • Mucosal immune system maintenance

Along with indigestible plant fibers, the epithelial cells shed by the intestine wall on a daily basis are utilized by local bacteria for sustenance and removal from the the gastrointestinal tract.

Postbiotic, prebiotic and probiotic food with medicine capsules. Set Super Healthy Fermented Food Sources, drinks, ingredients, on white marble background copy space top view

Clostridium difficile infection and FMT

Clostridium difficile colitis is a serious disease that causes severe diarrhea and in some cases, death. It causes a type of diarrhea called pseudomembranous colitis. In North America alone, approximately 29,000 patients died within 30 days of the initial diagnosis of Clostridium difficile colitis. Of those, about 15,000 deaths were estimated to be directly attributable to Clostridium difficile (CDC, 2015) i.e. from dehydration, toxic megacolon or bowel perforation.

Since its discovery as a bacteria that causes inflammation of the gut, Clostridium difficile has become an increasingly important pathogen. At first, C. difficile infections (CDI) were largely confined to patients who took antibiotic therapy over prolonged periods of time.

Standard antibiotic therapy for CDI is a course of vancomycin or metronidazole, but a significant portion of patients develop recurrent recurrent clostridium difficile infection (rCDI).

The high rates of recurrence, between 15% to 30% in some studies, posed a major challenge for health professional worldwide (Johnson, 2009). Many patients burdened by recurrent clostridium difficile infection experience:

  • repeatedly hospitalization,
  • frequent clinic visits,
  • deconditioning,
  • malnourishment,
  • fecal incontinence.

Antimicrobial treatment of recurrent clostridium difficile infection yields success rates of between 30% and 80%. For those who, despite treatment, had relapsing clostridium difficile infection fecal microbiota transplantation can yield possible respite.

A meta-analysis in 2016 reviewed a total of 2097 studies to determine whether FMT was an effective alternative treatment to standard treatment (switch to an alternative antibiotic treatment) Quraishi 2016. The researchers identified 37 studies which included 7 randomized control studies and 30 case series. The finding from this review were as follows:

  • Fecal transplants were more effective than vancomycin (an antibiotic treatment for Clostridium difficile) in resolving recurrent clostridium difficile infection
  • Clinical resolution across all studies was 92%
  • A significant benefit was observed between lower GI – via colonoscopy or fecal enemas, and upper GI delivery – via NG tube or capsule, of fecal microbiota transplantation (95% v 88% effective)
  • In patients with refractory clostridium difficile infection – or failed fecal microbiota transplantation, further fecal transplant gave an incremental beneficial effect.
  • Donor screening was consistently used, but there was variability in how the donor feces was prepared and the volume used.
  • Serious adverse events were uncommon.

The researchers concluded that fecal microbiota transplantation appeared to be an effective and safe treatment alternative to standard treatment.

Can FMT help with Inflammatory bowel disease?

Inflammatory Bowel Disease (IBD) is very common. There are 2 main similar conditions that come under the broad definition of IBD.  These are:

  1. Ulcerative Colitis (UC); and 
  2. Crohn’s disease (CD)

Both conditions involve long term, fluctuating inflammation of the gastro intestinal tract.  Some important difference between these 2 disease groups is that ulcerative colitis affects only the surface, or the mucosal layer of the colon, whereas Crohn’s disease affects anywhere from the mouth to the anus.

Common symptoms of inflammatory bowel disease

The typical symptoms of UC and CD  can have the following type of symptoms such as:

  • Intermittent or frequent diarrhea, with possible periods of constipation, 
  • abdominal pain and bloating.
  • Fever and fatigue
  • Weight loss
  • blood in the bowel motion

Additional issues to consider that inflammatory bowel disease is influenced by both genetics and lifestyle/environmental factors including:

There is increasing evidence suggesting that the intestinal microbiome plays a significant part in the the cause of IBD. There is an imbalance of bacteria in the bowel of the patient (gut dysbiosis), especially bacteria that is hostile to the gut and been known to provoke inflammation (Liu 2017)

Evidence for Ulcerative Colitis and FMT

A meta-analysis in 2019 reviewed 168 studies and found that fecal microbial transplantation led to a remission rate of 39.6% for UC (Lai 2019) A further systematic review and meta-analysis in 2020 confirmed that FMT is a potentially safe and well tolerated and efficacious treatment, with evidence for active ulcerative colitis being the strongest (Greene 2020).

It is worth noting that in some small case series, the clinical responses to FMT decreased over time with patients suffering from ulcerative colitis. In one recent case series;

  • 92% had a clinical response,
  • 75% achieved clinical remission,
  • 50% relapsed within 52 weeks of remission.

This suggests some patients would need retreatment over time to have continued benefit (Dang 2020).

Evidence for Crohn’s disease and fecal transplantation

In a meta-analysis published in March 2021 which included results from 12 trials, showed that

  • 38% of patients with Crohn’s disease experienced clinical remission (steroid-free)
  • 21% had clinical improvement in symptoms at follow-up.

It was worthy to note that in sub analysis, the use of fresh stool transplant was more likely to result in remission that use of frozen stool. There were no major FMT-related adverse events in the analysis. (Cheng 2021).

In one small randomized, single-blind, sham-controlled pilot trial of FMT in adults with Crohn’s disease. Granted that the study was small (n=17), but the results were encouraging. In the sham group steroid free remission at 10 weeks was 44% and 24 weeks was 33%.

The FMT group had steroid-free remission at 10 weeks of 88% and at 24 weeks of 50%. The concluding remarks from the researchers pointed out that higher colonization by doner FMT was associated with maintenance of remission. However, these results of this study needed to be confirmed by appeal to larger studies (Sokol 2020).

Irritable Bowel Syndrome and Fecal microbial transplantation

Irritable bowel syndrome (IBS) is a conglomerate functional diagnosis for those having symptoms in the digestive tract, but without identified gastrointestinal diseases. It is characterized by abdominal cramping, either or both of constipation and diarrhea.

In regards to irritable bowel syndrome and fecal microbiota transplant, meta-analysis of 5 studies showed there was no difference between controls and treatment in clinical outcomes (Green 2020).

Fecal microbiota transplant

Obesity, Metabolic Syndrome and the Microbiome

Recent evidence has demonstrated a connection between obesity and obesity-associated abnormalities with gut microbiome (Muscogiuri 2019). Along with increases in diet-derived energy production, it has been well studied that gut bacteria contributes to fatty acid regulation within tissues. Additionally the obesity associated gut microbiome contributes to chronic, low-grade inflammation, a classic hallmark of obesity (Ejtahed 2016).

Chronic systemic inflammation is greatly exacerbated when people consume high fat diets. It has been reported that high fat diets cause a shift in the balance of gut microbiota towards dysbiosis, with increased numbers of unfavorable Gram-negative bacteria. These gram negative bacteria with their lipopolysaccharide cell walls and metabolites are thought to contribute towards weight gain (Cani 2009).

A chronic low-grade inflammatory state can cause the intestinal barrier to become vulnerable and “leaky” as the intestinal tight junctions that act as part of the barrier, becomes more permeable due to the local inflammation. This leaky local inflammation results in impaired insulin signaling and leads to a state of insulin resistance over time. 

Use of fecal microbiota transplant in the treatment of metabolic syndrome and Type 2 diabetes is complex. Fecal microbial transplant has been demonstrated tp have favorable effects in mice studies. Fecal transfer showed that a “metabolically favorable” microbiota profile can be modeled  and used successfully to restore a “metabolically unfavorable” microbiota in correcting metabolic disorders (Wei 2020).

In human studies, the results have been less convincing, but changing the gut microbiome shows some promise for improving weight loss.

There has been 2 small randomized trials that have trialed FMT with patients with obesity. The first was a randomized, double masked study,  where researchers gave a single course of oral encapsulated fecal microbiome from 4 healthy lean donors and followed the participants over 26 weeks.

The study found that the gut microbiome profiling shifted among the group in the fecal microbiota intervention. Of those who had metabolic syndrome, fecal microbial transplant led to improved metabolic parameters compared to the placebo group (Leong 2020).

The second study was a 12 week double blinded randomized placebo-controlled pilot trial where patients with obesity were were given weekly oral FMT capsules from healthy lean doners for a period of 6 weeks and compared this to the placebo group. In this study the researchers did not observe clinically significant metabolic benefits during the study (Yu 2020)

Overall, since this is an emerging field, study duration is likely too short and human studies are small, the results are at best variable and further research is needed.

Importantly, diet is one of the most influential factors affecting the gut microbiota. In future research, interventions that target both FMT and a diet favorable to the microbiota, such as a whole food plant based diet high in fiber, are likely to be more capable of modifying gut bacteria longer term for long term reductions in chronic inflammation, and improvements in metabolic status.

What are the risks associated with Fecal Microbiota Transplantation (FMT)?

Fecal microbiota transplant

The main risks associated with FMT are listed below. These are 

  • Transmission of harmful pathogens
  • Unwanted immune responses
  • Dysbiosis (imbalance of gut microbiota)
  • Toxicity

A review and meta-analysis of all published research up to 21 March 2022 showed that FMT probably caused serious adverse events in less than 1% of patients (Rapoport 2022)

A review of four published randomized control studies with a total of 277 adults found there was no overall difference between the FMT group and the control group, but the following symptoms were noted (Imad 2018):

  • Abdominal pain
  • Nausea
  • Flatulence
  • Bloating
  • URTI
  • Headache
  • Dizziness and fever

Two US patients who received fecal microbiota transplantation from the same donor developed blood infections with an antibiotic resistant E. coli; one patient died. The donor was subsequently found to be a carrier of these bacteria. Both recipient patients were immune-compromised and both received antibiotic therapy around the same time of the FMT, which would have enhanced their risk with a resistant bacteria. The donor had not been screened for antibiotic-resistant E. coli before donating (DeFilipp 2019).

Who should not undergo Fecal Microbiota Transplantation (FMT)?

There is no one-size-fits-all answer to this question. Fecal microbiota transplant should not be undergone by people who are immunocompromised, have a serious illness, or are pregnant. Speak with your doctor to see if FMT is right for you.

References

Cani PD, Delzenne NM. The Role of the Gut Microbiota in Energy Metabolism and Metabolic Disease. Curr Pharm Des. 2009;15(13);1546-1558.

Cheng, F., Huang, Z., Wei, W. et al. Fecal microbiota transplantation for Crohn’s disease: a systematic review and meta-analysis. Tech Coloproctol 25, 495–504 (2021). https://doi.org/10.1007/s10151-020-02395-3

Dang XF, Qing-Xi Wang, Yin Z, et al. Recurrence of moderate to severe ulcerative colitis after fecal microbiota transplantation treatment and the efficacy of re-FMT: a case series. BMC Gastroenterol. 2020;20(1):401. Published 2020 Nov 26. doi:10.1186/s12876-020-01548-w

DeFilipp Z, Bloom PP, Torres Soto M, et al. Drug-Resistant E. coli Bacteremia Transmitted by Fecal Microbiota Transplant. N Engl J Med. 2019;381(21):2043-2050. doi:10.1056/NEJMoa1910437

Ejtahed HS, Soroush AR, Angoorani P, et al. Gut Microbiota as a Target in the Pathogenesis of Metabolic Disorders: A New Approach to Novel Therapeutic Agents. Horm Metab Res. 2016;48(06):349-358. DOI: 10.1055/s-0042-107792

Green JE, Davis JA, Berk M, et al. Efficacy and safety of fecal microbiota transplantation for the treatment of diseases other than Clostridium difficile infection: a systematic review and meta-analysis. Gut Microbes. 2020;12(1):1-25. doi:10.1080/19490976.2020.1854640

Han JL, Lin HL. Intestinal microbiota and type 2 diabetes: from mechanism insights to therapeutic perspective. World J Gastroenterol. 2014;20(47):17737-17745. doi:10.3748/wjg.v20.i47.17737

Imdad A, Nicholson MR, Tanner‐Smith EE, et al. Fecal transplantation for treatment of inflammatory bowel disease. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No.: CD012774. DOI: 10.1002/14651858.CD012774.pub2. Accessed 30 April 2022.

Johnson S. Recurrent Clostridium difficile infection: a review of risk factors, treatments, and outcomes. J Infect. 2009;58(6):403-410. doi:10.1016/j.jinf.2009.03.010

Khanna S, Tosh PK. A Clinician’s Primer on the Role of the Microbiome in Human Health and Disease. Mayo Clin Proc. 2014;89(1);107-114. https://doi.org/10.1016/j.mayocp.2013.10.011.

Lai CY, Sung J, Cheng F, et al. Systematic review with meta-analysis: review of donor features, procedures and outcomes in 168 clinical studies of faecal microbiota transplantation. Aliment Pharmacol Ther. 2019;49(4):354-363. doi:10.1111/apt.15116

Lee H, Lee, Jiyeon Kim, Jinho An, et al. (2018) Modulation of the gut microbiota by metformin improves metabolic profiles in aged obese mice, Gut Microbes. 2018;9(2);155-165. DOI: 10.1080/19490976.2017.1405209

Leong KSW, Jayasinghe TN, Wilson BC, et al. Effects of Fecal Microbiome Transfer in Adolescents With Obesity: The Gut Bugs Randomized Controlled Trial. JAMA Netw Open. 2020;3(12):e2030415. Published 2020 Dec 1. doi:10.1001/jamanetworkopen.2020.30415

Leustean AM, Ciocoiu M, Sava A, et al. Implications of the Intestinal Microbiota in Diagnosing the Progression of Diabetes and the Presence of Cardiovascular Complications. J Diabetes Res. 2018. https://doi.org/10.1155/2018/5205126

Liu H, Wu H, Chen Y, et al. Altered molecular signature of intestinal microbiota in irritable bowel syndrome patients compared with healthy controls: A systematic review and meta-analysis. Dig Liver Dis. 2017;49(4);331-337. https://doi.org/10.1016/j.dld.2017.01.142.

Muscogiuri, G., Cantone, E., Cassarano, S. et al. Gut microbiota: a new path to treat obesity. Int J Obes Supp 9, 10–19 (2019). https://doi.org/10.1038/s41367-019-0011-7

Napolitano M, Covasa M. Microbiota Transplant in the Treatment of Obesity and Diabetes: Current and Future Perspectives. Front Microbiol. 2020;11:590370. Published 2020 Nov 12. doi:10.3389/fmicb.2020.590370

Rapoport EA, Baig M, Puli SR. Adverse events in fecal microbiota transplantation: a systematic review and meta-analysis. Ann Gastroenterol 2022;35(2):150-163

Sokol H, Landman C, Seksik P, et al. Fecal microbiota transplantation to maintain remission in Crohn’s disease: a pilot randomized controlled study. Microbiome. 2020;8(1):12. Published 2020 Feb 3. doi:10.1186/s40168-020-0792-5

Wei Z, Shen P, Cheng P, Lu Y, Wang A, Sun Z. Gut Bacteria Selectively Altered by Sennoside A Alleviate Type 2 Diabetes and Obesity Traits. Oxid Med Cell Longev. 2020;2020:2375676. Published 2020 Jun 25. doi:10.1155/2020/2375676

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Yu EW, Gao L, Stastka P, et al. Fecal microbiota transplantation for the improvement of metabolism in obesity: The FMT-TRIM double-blind placebo-controlled pilot trial. PLoS Med. 2020;17(3):e1003051. Published 2020 Mar 9. doi:10.1371/journal.pmed.1003051

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