Faecal bacteriotherapy: faecal transplantation for clostridium difficile, colitis and Crohn's disease

By Cristiano Antonino On Mar 19, 2023

Faecal bacteriotherapy, also known as faecal transplantation or faecal transfusion or infusion of human probiotics (HPI) or faecal microbiome transplantation, is a non-pharmacological medical treatment, in an experimental phase, used with some efficacy in subjects suffering from pseudomembranous colitis sustained by the Clostridium difficile bacterium (recently renamed ‘Clostridium difficile’); or even in cases of ulcerative colitis refractory to common therapies

The aim of this innovative therapy is to restore the microbial ecology and homeostasis of the colon by reintroducing a healthy (balanced) human microbiota, taken from the faeces of a healthy donor or in certain cases from faeces previously ‘donated’ by the same subject (homotransfusion or autologous restoration of gastrointestinal flora – ARGF).

The theoretical rationale for this therapeutic technique is to be found in the most advanced research on the use of probiotics and studies on the microbiome, which is the set of microorganisms: bacteria, archaeobacteria, fungi, viruses, present in a specific environment (in this case the faecal environment).

It is well known how a good microbial ecology can repel the overgrowth of pathogenic organisms.

In the colon, it is estimated that there are 500 to about 1000 different species of bacteria with a total of 1013 bacteria.

In fact, the microbiome should be considered as a biological entity in its own right, which is symbiont with the host organism.

The bacteria complex or microbiome acts in maintaining the homeostasis of the host organism; this microbial flora is relatively harmless when reintroduced into the body.

Not much is known about the role of the microbiome, however, many herbivorous and non-herbivorous animal species are known to have coprophagic habits, probably due to having a double digestive cycle (double digestion).

Faecal transplantation: the main advantage of faecal bacteriotherapy is to reduce the risk of inducing antibiotic resistance in highly pathogenic bacteria

Other advantages are a relatively low cost, no need for drugs and good efficacy (to be confirmed – however – with larger studies) for the treatment of cases where antibiotic resistance exists.

However, the method is still considered a treatment of ‘last resort’ due to its greater invasiveness compared to conventional treatment with antibiotics, and the potential risks of infection transmission (bacteria, viruses, prions, intestinal parasites).

Although experience with faecal bacteriotherapy is still limited, published results on the procedure show that over 80 patients have demonstrated an average success rate of over 90%

Faecal bacteriotherapy is a low-tech, easy-to-perform procedure that can break cycles of repeated antibiotic use, which in turn reduces the risk of the recently increasing occurrence of antibiotic resistance.

It also has the potential to save costs, compared to repeated antibiotic administrations with the necessary hospitalisations.

Pseudomembranous colitis

The importance as a pathogen of Clostridium difficile (CDI) has been firmly established since 1978, but the importance of this technique 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 (CDI) have doubled from 31/100,000 in 1996 to 61/100,000 in 2003.

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

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 C. difficile are responsible for the majority of recent nosocomial outbreaks, and the widespread use of fluoroquinolone 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.

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

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

The increased frequency of infections by hypervirulent C. difficile strains has led to complications and therapeutic failures with conventional 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 lacking to date.

Ulcerative colitis

In ulcerative colitis, no pathogen has been found to date.

But the effectiveness 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 has remained 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.

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

This study demonstrates the tolerability and efficacy 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.

Faecal transplantation, other diseases studied for faecal bacteriotherapy

The technique is currently being studied in subjects with Parkinson’s disease, diabetes, obesity, irritable bowel syndrome, chronic inflammatory bowel disease, multiple sclerosis, idiopathic thrombocytopenic purpura, Crohn’s disease, insulin resistance and chronic fatigue syndrome.

Classic procedure

Normally the faeces of a close, healthy relative of the patient is used after investigating and excluding the presence of contagious bacteria or viruses or parasites such as: Salmonella, hepatitis virus, etc.

After collection, the stool sample is processed and prepared in a clinical laboratory in the form of a liquid suspension, which is then instilled into the upper gastrointestinal tract via a nasogastric tube that goes up to the level of the cecum.

The procedure sometimes involves 5-10 days of treatment with enemas, made with human microbiota from the faeces of a healthy donor; most patients recover after only one treatment.

The best choice of donor is a close relative that has been tested for a wide range of bacterial and parasitic agents.

The enemas are prepared and administered in a hospital environment to ensure all necessary care.

Infusion of the probiotic can also be done through a nasogastric tube, delivering the bacteria directly to the small intestine.

The two methods can be combined to achieve the best result.

Regular check-ups should be done up to one year after the procedure.

ARGF (autologous restoration of gastrointestinal flora)

A modified form of faecal bacteriotherapy, currently under development, is autologous restoration of gastrointestinal flora – (ARGF).

This method is safer, more effective and easier to administer.

An autologous (own) faecal sample is provided by the patient before medical treatment and stored in a refrigerator.

If the patient subsequently develops C. difficile pathology, the sample is extracted with saline and filtered. The filtrate is lyophilised and the resulting solid is enclosed in gastro-resistant capsules.

The administration of the capsules restores the patient’s own colonic flora, which is useful in combating any C. difficile infection that may have set in.

This procedure avoids the risks of classic faecal bacteriotherapy, where a possible infection could be transmitted to the patient by the donor, and also avoids the need to administer the faecal sample into the duodenum via a gastric probe.

Efficacy

The effectiveness of the method in preventing recurrences of pseudomembranous colitis is estimated to be around 90%.

A study from December 2011 confirms these data showing an efficacy of the method of 92% in preventing diarrhoea or further recurrence in a group of 26 patients with recurrent C. difficile infections.

A Finnish study from 2011 points out that antibiotic treatment of recurrent Clostridium difficile infections (CDI) leads to recurrences in 50% of patients.

The use of faecal transplantation during a colonoscopy test procedure after an intestinal preparation with polyethylene glycol (lavage) resulted in a resolution of 89% of cases of recurrent pseudomembranous colitis at one-year follow-up, emphasising that the treated cases were caused by a particularly virulent C. difficile strain (type 027).

Also in December 2011, a review of 317 patients showed 92% efficacy of the method, also showing few side effects.

In 2015, a comparison study with vancomycin was published showing the superiority of bacterial faecal therapy over this antibiotic.

Colitis: Symptoms, Treatment And What To Eat

Ulcerative Colitis: Causes, Symptoms And Treatment

A Baby’s Gut Bacteria May Predict Future Obesity

Faecal Microbiota Transplantation (Faecal Transplantation): What Is It For And How Is It Performed?

Sant’Orsola In Bologna (Italy) Opens A New Medical Frontier With Microbiota Transplantation

Microbiota, The Role Of The ‘Gate’ That Protects The Brain From Intestinal Inflammation Discovered

What Are The Differences Between Diverticulitis And Diverticulosis?

What Is Breast Needle Biopsy?

Colonoscopy: The Latest Techniques And Various Types

Dysbiosis And Hydrocolon Therapy: How To Restore Intestinal Well-Being