REVITALIZING GUT HEALTH: FECAL TRANSPLANT FOR C. DIFF AND BEYOND

Fecal microbiota transplantation or FMT is a novel treatment option for those suffering from a severe form of a common gastro bug. Those suffering from recurrent C. diff infections may not see results from normal antibiotic treatment, which may even exacerbate their symptoms or lead to life-threatening complications.

In this article, FMT is explored as a cutting-edge C. diff treatment that aims to restore the integrity of the gut microbiome. C. diff symptoms and causes are discussed alongside how FMT works as a treatment. The scope of FMT for treating other conditions caused by imbalances in the gut microbiome is also covered.

What is C. Diff?

C. diff, or Clostridium Difficile, is a type of bacteria that can colonize the gut, causing recurrent colon infections that sometimes lead to life-threatening complications. It is one of the most common hospital-acquired infections and is most frequently seen in patients on long-term antibiotics or those with a weakened immune system.

C. Diff Symptoms

Clostridium Difficile symptoms can range from mild to severe and may last for weeks or months.^[1]

Common symptoms of C. diff infection include:

• Watery diarrhea
• Abdominal pain and cramps
• Nausea and vomiting
• Fever
• Bloating
• Loss of appetite

If prolonged, a C. diff infection can lead to serious and sometimes life-threatening complications, such as dehydration, kidney failure, colon damage, a toxic megacolon (enlarged colon that may rupture), and sepsis.

Diagnosis

When symptoms are present, a doctor will order stool sample testing to confirm the presence of C. diff, especially if the patient’s symptoms are persistent after being treated with antibiotics.

There are different types of tests that can detect C. diff infection^[2]:

• ELISA Test (Enzyme-Linked Immunosorbent Assay) that detects C. diff antibodies, toxins or proteins.
• Cell cytotoxicity Assay Test that checks the effects of bacterial toxins on cells, identifying C. diff-specific patterns.
• PCR Test that checks for bacterial genes linked to C. diff bacteria.
• GDH Antigen Test that looks for GDH antigens (specific C. diff proteins) and can determine if you carry spores.
• Lab Culturing, which involves growing C. diff from a stool sample, can also reveal the infection’s severity.

Some of the above tests may require specialized laboratory equipment and are not widely available.

Your doctor may also need to rely on blood tests, a CT scan or endoscopy to check and assess possible C. diff complications, such as colonic enlargement, a toxic megacolon or a hole in the lining.

How C. Diff Infects the Gut

The gut microbiome, which comprises friendly bacteria, is already home to more than 20 strains of probiotic (beneficial) clostridium bacteria that typically reside in the colon. These are among the first bacteria to colonize our guts during infancy and form an important component of breast milk. Healthy clostridium species help to maintain the balance of bacteria in the gut, promote bile acid secretion and support optimal digestion.

C. diff infection occurs when the normal balance of clostridium bacteria in the gut is disrupted by antibiotics or other factors, allowing C. diff to grow and produce toxins that damage the intestinal lining.

Clostridium Difficile Hides Among Normal Flora. Clostridium difficile is regarded as an opportunistic pathogen that resides ubiquitously in soil and feces. When conditions are not suitable, it goes into a spore mode, rendered completely inactive and harmless. While not considered as part of the human microbe collective, it is estimated that 1-3% of the human microbiome might consist of C. diff spores across the global population.^[3]

Normal Clostridium Keeps C. Diff At Bay. The presence of healthy clostridium species helps to keep C. diff spores inactive by converting primary bile acids into secondary bile acids, which creates an inhospitable environment for C. diff.^[4] They are also thought to outnumber C. diff and outcompete it for nutritional resources.

C. Diff Activates with Gut Dysbiosis and Impaired Digestion. General antibiotics can destroy normal clostridium species, alongside long-term exposure to other factors, including pollutants, chemicals, pesticides, various medications, and a diet that leads to the suppression of digestive juices. Low stomach acid coupled with incomplete conversion of bile and reduced probiotic microbes allows for C. diff spores to activate, leading to a C. diff infection.

Chronic C. Diff Takes Over the Gut. C. diff is renowned for releasing toxins that actively destroy the intestinal wall and kill off healthy gut bacteria. Chronic C. diff infections are thought to be connected to IBS and other gastrointestinal diseases. If prolonged, C. diff can eventually colonize the colon, making it very difficult to treat without re-establishing the colonic microbiome.

When FMT Beats Standard C. Diff Treatment

Conventional C. diff treatment includes antibiotics that specifically target C. difficile^[5]. While this is often beneficial for low-grade infections, it does not get rid of C. diff spores and may accidentally target other beneficial strains of clostridia. This is likely why those with recurrent infections do not see much success, as their gut does not properly repopulate with the right bacteria before C. diff begins to grow back again.

A course of clostridium-containing probiotics or colostrum can help to correct any residual microbiome imbalances in mild cases. For chronic C. diff infections that are resistant to standard antibiotic treatment, probiotics may not be sufficient to correct the problem in time. This is where a fecal microbial transplant is recommended.

What is a Fecal Transplant?

Fecal Microbiota Transplantation (FMT) is a procedure that involves transferring healthy colonic bacteria from a suitable donor to the colon of a patient who requires treatment. Other names for an FMT include a fecal matter transplant or stool transplant, as the bacteria are extracted from a purified stool sample before being administered to the patient.^[6]

It is currently most commonly used for treating resistant C. diff infections, although it is still regarded as an experimental therapy.

Bacterial delivery for FMT can be performed in different ways, such as by colonoscopy, enema, capsule, or nasogastric tube. The donor stool is screened prior to the procedure for pathogens, toxins and disease biomarkers and processed in a laboratory before being administered to the patient.

How Does a Fecal Transplant Work?

A fecal transplant works by restoring the natural diversity of bacterial species to the colon. The millions of microbes extracted from the stool sample recolonize the recipient’s gut with beneficial microbes that they lack. This improves digestion and immunity. It also suppresses C. diff growth.^[7]

What Health Conditions Can FMT Treat?

FMT has proven to be highly effective in treating C. diff infection, especially in cases that are recurrent or resistant to antibiotics. Across several studies, FMT achieved a cure rate of between 75-92% for C. diff infection^[8], compared to 22-50% for antibiotics^[9]. FMT also had fewer adverse events and costs less than antibiotics in the long run.

There is evidence to suggest that FMT is also a potential therapy for other conditions that involve an unbalanced gut microbiome, such as:^[10]

• Inflammatory bowel disease, including Crohn’s disease and ulcerative colitis
• Irritable bowel syndrome
• Liver disease
• Obesity and diabetes
• Autism spectrum disorder
• Anxiety disorders and depression
• Multiple sclerosis
• Severe food allergies^[11]

Research is ongoing to establish the safety and efficacy of FMT for these indications.

Fecal Transplant Procedure

A fecal transplant is usually over within minutes and requires minimal preparation on the recipient’s part. One prepares for the procedure by taking antibiotics to reduce C. diff in their colon a few days beforehand and undergoing bowel cleansing with laxatives or enemas (not required if opting for an FMT enema procedure).

The procedure can be administered in any one of the following ways:

• Colonoscopy: In this procedure, a flexible tube with a camera and a light is inserted through the anus and advanced to the end of the colon. The FMT solution is then injected into the colon through the tube. The patient may be given a sedative and painkiller for the procedure.
• Enema: A tube is inserted into the rectum, and the FMT solution is delivered into the lower part of the colon.
• Nasogastric tube: A thin tube is inserted through the nose and down to the stomach or the small intestine. The FMT solution is then pumped through the tube into the digestive tract. The patient may be anesthetized for this procedure.
• Capsule: The FMT solution is encapsulated in pills that are swallowed by the patient at home. The capsules dissolve in the small intestine and release the FMT solution into the colon.

The doctor may ask that the patient stay under observation at the facility for a few hours after the procedure to monitor for any adverse reactions or complications. After the patient is released, they may resume their normal diet and activities.

It is essential to follow up with a doctor in the weeks following an FMT to evaluate improvement or recurrence of C. diff infections. Some patients may need more than one FMT session to achieve optimal results.

Fecal Transplant Donor Screening

The fecal transplant donor is carefully screened for any diseases or infections that could be transmitted through the stool. They may need to supply a medical history and go for blood tests and stool testing. Potential donors are also screened for certain lifestyle factors, such as recent travel and drug use.

Volunteers can be denied as fecal transplant donors if they have:

• Antibiotic-resistant bacteria, such as E. Coli
• Viral infections, including SARS‑CoV‑2, HIV or Epstein-Barr virus
• Parasites
• Had recent antibiotic treatment within the last 3 months
• IBD
• Autoimmune diseases
• Metabolic disorders
• Cancer or a family history of cancer

The donor should be a healthy person who has not taken antibiotics for at least three months.

Sample Preparation

The donor’s FMT solution is purified by mixing the stool sample with saline water and filtering it to remove any solid particles. The stool mixture is then tested for any pathogens or infections that could be harmful to the recipient. The mixture is then purified in line with strict guidelines. The purification process aims to ensure the safety and quality of the FMT solution and to preserve the beneficial bacteria that can restore the gut microbiome balance.

After purification, the FMT solution is ready to be transferred into the colon of the patient, formulated into capsules or saved aside at a donor bank for later use.

FMT Risks and Complications

The procedure is generally regarded as very safe and effective, especially for treating recurrent C. diff infection. Risks and complications are rare and include infection, bowel damage and allergy.

The guidelines for FMT have been updated in the US after it was shown to induce resistant E. Coli infections in a handful of recipients.^{[12] [13]}

To minimize risks and complications, it is important to ensure:

• The donor screening and stool testing are very rigorous and follow the guidelines and regulations of the relevant authorities.
• The FMT procedure is performed by trained and experienced medical professionals who follow strict hygiene and infection control measures.
• The patient is monitored afterward for signs of infection or allergy and tested if symptoms occur.

Unknown Long-Term Effects. One drawback of FMT is that it can alter gut microbiome composition and function in ways that are not fully understood. This can have a positive or negative impact on the health and well-being of the recipient, as the microbiome helps to shape the immune system, metabolism, mood, behavior, and susceptibility to other diseases. More research is necessary to ascertain the long-term safety and efficacy of FMT for different conditions.

Despite these considerations, FMT is still one of the most efficacious treatments for recurrent C. diff and may even be curative in some cases.

Future Therapies to Complement FMT for Chronic C. Diff Infections

There are other treatments currently under investigation for treating C. diff that may become complementary to FMT in the future. These include:

Probiotics and Colostrum have been shown in a small-scale trial to completely eliminate C. diff toxins in most patients supplementing with them after 2 weeks^[14]. While not strictly approved for treating C. diff, patients may still benefit from using these food-grade supplements alongside other treatments. Colostrum is a probiotic formulation designed to promote clostridium diversity in the gut.

Bezlotoxumab is the first antibody for the secondary prevention of recurrence of C. diff infection approved by regulatory agencies in the US and Europe. It is a human monoclonal antibody that is administered systemically to patients receiving oral standard-of-care antibiotics. It can bind to C. diff toxin B and prevent it from damaging the intestinal lining.^[15]

Antibody-enriched Colostrum for C. diff is a novel, orally delivered antibody therapy that is in an advanced clinical development stage. While not yet approved for medical use, it has shown promising results in preventing C. diff infection in pre-clinical models. The therapy involves transferring antibodies from bovine colostrum (the first milk produced by cows after giving birth) to the colon of patients with C. diff infection. The antibodies can neutralize the toxins produced by C. diff bacteria and restore the balance of the gut microbiome.^[16]

When to Consult with a Professional for FMT

FMT is not a one-size-fits-all solution. Individual factors such as donor selection, preparation method, delivery route, and frequency may affect the outcome.

If you are interested in FMT as a treatment option for C. diff infection or other conditions, consider consulting your doctor about the benefits and risks, as well as the availability and regulations of FMT in your area.

Conclusion

FMT is a novel and promising treatment for C. diff infection that offers advantages over conventional antibiotics. By restoring the balance of the gut microbiome, FMT can help patients overcome C. diff infection and improve their quality of life. However, it is worth noting that while treatments altering the microbiota have existed for over a millennia^[17], Fecal Microbiota Transplantation is currently regarded as experimental, with ongoing research into its efficacy and other prospective use cases.

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