Faecal microbiota transplantation (faecal transplantation): what is it for and how is it performed?

By Cristiano Antonino On Feb 28, 2023

Faecal microbiota transplantation (also known as ‘faecal transplantation’) in medicine refers to the process by which faecal bacteria and other microbes are transferred from one healthy individual to another

Faecal microbiota transplantation is an effective treatment for infection caused by the bacterium Clostridioides difficile (CDI)

This bacterium was known until a few years ago as Clostridium difficile.

For recurrent infections caused by this bacterium, faecal microbiota transplantation is more effective than therapy with the antibiotic vancomycin.

Side effects may include the risk of infection, so the donor must be screened.

Faecal microbiota transplantation involves restoring the colonic microflora by introducing healthy bacterial flora through the infusion of faeces via colonoscopy, enema, orogastric tube or orally in the form of a capsule containing the faeces of a healthy donor, which in some cases is freeze-dried.

With the spread of CDI, faecal microbiota transplantation is becoming increasingly important, with some experts calling for it to become the first-line therapy for CDI.

Faecal microbiota transplantation has been used experimentally to treat other gastrointestinal diseases, including colitis, constipation, irritable bowel syndrome and neurological conditions, such as multiple sclerosis and Parkinson’s.

In the US, human faeces has been regulated as an experimental drug since 2013.

In the UK, regulation for faecal microbiota transplantation is the responsibility of the Medicines and Healthcare products Regulatory Agency.

To date, the Operative Unit of Gastroenterology at the Policlinico Gemelli in Rome, directed by Prof. Antonio Gasbarrini, is the only one in Italy to count faecal microbiota transplantation among the available treatment options for patients with relapsing Clostridioides difficile infection.

What is the faecal microbiota?

The ‘human microbiota’ is the collection of symbiotic micro-organisms (viruses, bacteria and fungi) that coexist with the human organism without harming it, but rather supporting it, in a mutually beneficial relationship.

The human gut microbiota is the part of the human microbiota in the gut that is important for our health.

The ‘human gut microbiota’ is also called the ‘human intestinal microbiota’ or ‘faecal microbiota’ and is mostly composed of bacteria.

It used to be referred to as ‘intestinal flora’ but, as it is composed of more than just bacteria and as bacteria do not belong to the plant kingdom, the name has been changed.

Historical background

The first use of donor faeces as a therapeutic agent for food poisoning and diarrhoea was recorded in the Manual of Emergency Medicine by the Chinese Ge Hong in the 4th century BC.

Two hundred years later, Ming dynasty physician Li Shizhen used ‘yellow soup’ (also called ‘golden syrup’) that contained water and fresh, dried or fermented faeces.

The yellow soup was drunk by people who showed symptoms of abdominal discomfort.

The consumption of ‘fresh, hot camel faeces’ was also recommended by Bedouins as a remedy for bacterial dysentery; its efficacy probably attributable to the antimicrobial subtilisin produced by Bacillus subtilis was anecdotally confirmed by German soldiers of the Afrika Korps during World War II.

However, this story is probably a myth; independent research has not been able to verify any of these claims.

The first use of faecal microbiota transplantation in Western medicine was published in 1958 by Ben Eiseman and colleagues, a team of Colorado surgeons, who treated four critically ill people with fulminant pseudomembranous colitis (before Clostridioides difficile was the known cause) using faecal enemas, which led to a rapid return to health.

For over two decades, faecal microbiota transplantation was provided as a treatment option at the Centre for Digestive Diseases in Five Dock, by Thomas Borody, the modern proponent of faecal microbiota transplantation.

In May 1988, their group treated the first patient with ulcerative colitis using faecal transplantation, which resulted in complete resolution of all signs and symptoms in the long term.

In 1989, they treated a total of 55 patients with constipation, diarrhoea, abdominal pain, ulcerative colitis and Crohn’s disease with faecal microbiota transplantation.

After transplantation, 20 patients were considered ‘cured’ and 9 other patients had a reduction in symptoms.

Faecal transplants are considered about 90% effective in those with severe cases of Clostridioides difficile colonisation in which antibiotics have failed.

The first randomised controlled trial on Clostridioides difficile infection was published in January 2013.

The study was stopped early due to the efficacy of faecal microbiota transplantation, with 81% of patients achieving recovery after a single infusion and over 90% achieving recovery after a second infusion.

Since then, various institutions have offered faecal microbiota transplantation as a therapeutic option for a variety of conditions.

Medical uses

Clostridioides difficile infections

Faecal microbiota transplantation is effective for approximately 85-90% in people with CDI for whom antibiotics have not worked or in whom the disease recurs after taking antibiotics.

Most people with CDI recover with faecal microbiota transplantation treatment.

A 2009 study found that faecal microbiota transplantation was an effective and simple procedure that was more cost-effective than continuous antibiotic administration and reduced the incidence of antibiotic resistance.

Until a few decades ago, this procedure was considered a ‘therapy of last resort’ by some medical professionals, due to its unusual nature, the taboos associated with faeces, its greater invasiveness compared to antibiotics, the perceived potential risk of infection transmission, and the lack of faecal coverage by donors.

Currently, on the contrary, numerous position statements of infectious disease specialists and gastroenterologists are moving common feeling towards the acceptance of faecal transplantation as standard therapy for CDI recurrences.

For some physicians it is necessary to elevate faecal microbiota transplantation as a first-line treatment for people with deteriorating and severe relapsing Clostridioides difficile infection.

Ulcerative colitis

In ulcerative rectocolitis, no pathogen has been found so far.

But the efficacy of faecal bacteriotherapy in this case would suggest that the cause of ulcerative colitis may be due to a previous infection with a pathogen that remains unknown.

Indeed, the initial infection may probably have resolved naturally in these patients; but sometimes, an imbalance in the intestinal flora of the colon may lead to an inflammatory flare-up (which would explain the cyclic and recurrent nature of this disease).

This cycle seems, at least in many cases, to be interrupted by re-colonising the patient’s colon with a bacterial complex (probiotic) taken from a healthy intestine (heterograft).

Some doctors believe that this treatment carried out in healthy subjects is safe and many patients could benefit from this innovative therapy.

A study in May 2011 confirmed the good willingness of patients and parents of children with ulcerative colitis to accept this treatment, once they had overcome their initial distaste for the method.

“Although initial disgust and the ‘puah factor’ were uniformly cited, these concerns were more than offset by perceived benefits.”

(Kahn et al., University of Chicago)

In 2013, another research confirms the validity of the therapy with a prospective pilot study of ten subjects aged 7-21 years.

This study demonstrates the tolerability and effectiveness of faecal transplantation therapy in ulcerative colitis; in fact, in seven subjects there was clinical remission within one week and six out of nine maintained clinical remission at one month.

A May 2011 study confirmed the good willingness of patients and parents of children with ulcerative colitis to accept this treatment, once they had overcome their initial distaste for the method.

In May 1988, Australian professor Thomas Borody treated the first patient with ulcerative colitis using faecal microbiota transplantation, which led to a resolution of long-standing symptoms.

Subsequently, Justin D. Bennet published the first case report documenting the reversal of Bennet’s colitis using faecal microbiota transplantation.

Although Clostridioides difficile is easily eradicated with a single faecal transplant infusion, this generally does not seem to be the case for ulcerative colitis.

Published experience on the treatment of ulcerative colitis with microbiota transplantation largely shows that multiple, recurrent infusions are necessary to achieve a prolonged remission or cure.

Pseudomembranous colitis

The importance as a pathogen of Clostridioides difficile has been firmly established since 1978, but its importance in the treatment of pseudomembranous colitis also stems from the fact that its epidemiology has recently changed, posing serious diagnostic and therapeutic problems for clinicians.

Infection rates have doubled from 31/100,000 in 1996 to 61/100,000 in 2003.

In recent years, the severity and mortality of Clostridioides difficile infection has been increasing and this has been attributed to a new virulent strain of Clostridioides difficile known as the North American Pulsed-field gel electrophoresis type 1 (NAP-1) strain or also PFGE type BI/NAP1 ribotype 027.

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The uniqueness of the NAP-1 strain lies in its increased production of toxins A and B and its binary toxin production and resistance to fluoroquinolone.

Hypervirulent NAP1 strains of Clostridioides difficile are responsible for the majority of recent nosocomial outbreaks, and the widespread use of fluoroquinolone-type antibiotics may have facilitated the selective proliferation of this strain.

The NAP1 strain is also more likely to cause severe, fulminant colitis characterised by marked leucocytosis, acute renal failure, haemodynamic instability, and toxic megacolon.

Clostridioides difficile has become the most common bacterial cause of nosocomial diarrhoea.

Clostridioides difficile infection causes CDAD (Clostridioides difficile Associated Disease) or more rarely pseudomembranous colitis, which is a serious medical condition causing significant morbidity and mortality, especially in patients undergoing antibiotic treatment or cancer patients undergoing stem cell transplantation, or even in patients undergoing radiotherapy.

The increased frequency of infections by hypervirulent Clostridioides difficile strains has led to complications and therapeutic failures with traditional treatment with metronidazole and vancomycin.

Although with limited clinical experience, faecal bacteriotherapy has preliminarily been shown to provide high clinical cure rates, however, randomised clinical trials for this therapeutic approach are currently lacking

Faecal microbiota transplantation against obesity and diabetes

The latest frontier of faecal microbiota transplantation is the fight against obesity and diabetes.

In fact, this therapy could be proposed to lose weight and to fight type 2 diabetes mellitus, as suggested by a study from the University of Copenhagen.

The results are promising, for now, on laboratory mice.

In the research, the scientists tested on mice a new type of faecal transplantation that consists of transferring only bacteriophage viruses present in the animals’ faeces samples, excluding bacteria.

The researchers extracted faeces from mice fed a low-fat diet and filtered it so as to remove all live bacteria, while retaining the bacteriophage viruses.

The resulting material was transplanted into the intestines of the overweight mice, which continued to feed as before for a further six weeks.

The results showed that the strategy was effective: the recipients reduced fat accumulation despite having eaten the same foods as before and saw their risk of developing glucose intolerance, one of the conditions that favour the onset of diabetes, decrease.

Prof. Dennis Sandris Nielsen, one of the study’s authors, said: ‘When we transfer virus particles from the faeces of lean mice to obese mice, the obese mice gain significantly less weight than those that do not receive the transplanted faeces.

Another author of the study, Prof. Torben Sølbeck Rasmussen, said: ‘In obese mice with a high-fat diet that did not receive the virus transplantation, we observed reduced glucose tolerance, a factor that is a precursor to diabetes.

But by intervening in the gut microbiome, we have prevented mice with unhealthy lifestyles from developing some of the common diseases triggered by poor nutrition’.

Cancer and faecal microbiota transplantation

Clinical trials are underway to evaluate whether faecal microbiota transplantation from anti-PD-1 immunotherapy donors can promote a therapeutic response in patients refractory to immunotherapy.

Faecal microbiota transplantation and bipolar disorder

An anecdotal case of a patient with treatment-resistant Bipolar 1 Disorder resolving her symptoms with faecal microbiota transplantation was published by psychiatrist Russell Hinton in 2020.

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