How Poop Is Saving Lives: The Research Behind Fecal Transplant

Reboot Your Gut - Explore how this centuries old remedy is treating today’s toughest gut infections & chronic diseases

Fecal Microbiota Transplantation (FMT)

Fecal microbiota transplantation is an ancient therapy for modern medicine: Exploring the science, history and future applications of fecal transplants in treating gut related disorders and chronic diseases.

What is a Fecal Transplant?

• Fecal microbiota transplantation (FMT), also known as stool transplant or bacteriotherapy, is a medical procedure involving the transfer of stool from a healthy donor into the gastrointestinal tract of a recipient.

• This technique is primarily utilized to treat recurrent Clostridioides difficile (C. difficile or C. diff) infections, particularly in cases where conventional antibiotic treatments have failed.

• During the procedure, a stool sample is collected from a thoroughly screened donor, mixed with a sterile saline solution, and then filtered to produce a liquid suspension. This suspension is then administered to the patient via colonoscopy, enema, or a nasogastric tube, depending on the clinical situation.

• FMT has shown remarkable effectiveness in treating recurrent C. difficile infections, with success rates exceeding 90%. However, it is generally reserved for patients with persistent or severe infections.

• Notably, FMT has been used successfully even in very young patients, including infants as young as 13 months.

Understanding Clostridioides difficile

• C. difficile is a spore-forming, gram-positive, anaerobic bacillus that produces toxins capable of causing a range of gastrointestinal symptoms, from mild diarrhea to life-threatening conditions such as pseudomembranous colitis, toxic mega colon, and septic shock.

• Infection typically occurs after the use of antibiotics, which disrupt the normal gut microbiota and allow C. difficile to proliferate. The bacterium is highly resilient, with spores that can survive on surfaces for long periods and are easily transmitted through contaminated hands, especially in healthcare settings.

• C. difficile is responsible for approximately half a million infections annually in the United States alone, underscoring its significance as a public health concern.

Risk factors for infection include:

• Recent or prolonged use of antibiotics or proton pump inhibitors

• Immunosuppression

• Advanced age

• Hospital or nursing home stays

de Groot PF & et al. Fecal microbiota transplantation in metabolic syndrome: History, present and future. Gut Microbes. 2017;8(3):253-267.

Ancient History of FMT

• The concept of fecal transplantation is not new. Its roots trace back to ancient China during the 4th century CE, where physicians used preparations like "yellow soup" to treat food poisoning and severe diarrhea. By the 16th century, Chinese medical texts described various fecal-based remedies for gastrointestinal ailments.

• Elsewhere, Bedouin communities were known to ingest camel feces to treat dysentery. In Europe, the Italian surgeon Andrea Acquapendente (1537–1619) introduced "transfaunation” is the transfer of gut contents from healthy to ill animals which is an approach that found applications in veterinary medicine.

• Further uses of human feces in therapy were documented in the 18th and 19th centuries and even during World War II, when German soldiers suffering from dysentery in North Africa were treated with gut bacteria-based therapies.

Mechanisms of Action: How FMT Works

The primary goal of FMT is to restore a balanced and diverse microbial community in the gut. This is achieved by reintroducing healthy bacteria that:

• Regulate immune and inflammatory responses

• Normalize neurotransmitter levels

• Improve energy metabolism

• Enhance gut barrier integrity and reduce intestinal permeability ("leaky gut")

• Suppress pro-inflammatory pathways and stimulate beneficial T-cell activity

• By replicating the healthy microbiota profile of the donor, FMT helps re-establish gut homeostasis and mitigates disease severity.

Evidence from Clinical Research

Study on Recurrent C. difficile Infection

A pivotal randomized controlled trial assessed the effectiveness of duodenal infusion of donor feces in patients with recurrent C. difficile infection. Patients were assigned to one of three groups:

1. Oral vancomycin + bowel lavage + fecal infusion

2. Standard oral vancomycin

3. Oral vancomycin + bowel lavage

The fecal infusion group showed a 94% success rate after one or two infusions. In contrast, only 31% of the oral vancomycin group and 23% of the vancomycin plus lavage group achieved complete resolution.

The study concluded that FMT is significantly more effective than antibiotic therapy alone in resolving recurrent C. difficile infections.

Additional Research on Metabolic Conditions

• In another randomized, double-blind, placebo-controlled cross-over trial, 101 children and adolescents (aged 6–18) with obesity and insulin resistance received probiotic or placebo treatments.

• After eight weeks of probiotic therapy and a four-week washout, the probiotic group showed improved insulin sensitivity and glucose metabolism. These findings support the potential role of microbiota-based therapies in metabolic disorders.

Expanding the Therapeutic Scope of FMT

Beyond C. difficile, ongoing research explores the use of FMT in a variety of conditions, including:

1. Autism spectrum disorder (ASD)

2. Non-alcoholic fatty liver disease (NAFLD)

3. Irritable bowel syndrome (IBS)

4. Inflammatory bowel disease (IBD)

5. Type 2 diabetes

6. Functional constipation

While promising, more rigorous clinical trials are necessary to establish safety, efficacy, and optimal protocols for these broader applications.

Side Effects of Fecal Microbiota Transplantation (FMT)

• The U.S. Food and Drug Administration (FDA) has issued a public safety communication regarding the potential risk of serious or life-threatening infections associated with fecal microbiota transplantation (FMT).

• The FDA reported that six patients developed infections caused by enteropathogenic Escherichia coli (EPEC) and Shigatoxin-producing Escherichia coli (STEC) following FMT procedures using material supplied by a commercial stool bank.

• Among these cases, four patients were hospitalized and two patients with underlying chronic health conditions received FMT products from a donor linked to STEC infections and subsequently died.

Conclusion

• Fecal microbiota transplantation represents a transformative approach in the treatment of gastrointestinal and systemic conditions associated with dysbiosis. Its proven efficacy in managing recurrent C. difficile infections highlights the therapeutic power of the gut microbiome.

• While the concept has ancient origins, modern scientific validation has positioned FMT as a powerful tool in both infectious disease management and potentially a wide array of chronic illnesses. Continued research and regulation are essential to unlocking its full potential across diverse medical conditions.

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References:

Kelly CR, Allegretti JR. Review Article: Gastroenterology and Clostridium difficile Infection: Past, Present, and Future. Clin Infect Dis. 5;77(Suppl 6):S463-S470.

Antushevich H. Fecal microbiota transplantation in disease therapy. Clin Chim Acta. 2020;503:90-98.

Shen ZH, Zhu CX, Quan YS, Yang ZY, Wu S, Luo WW, Tan B, Wang XY. Relationship between intestinal microbiota and ulcerative colitis: Mechanisms and clinical application of probiotics and fecal microbiota transplantation. World J Gastroenterol. 2018;24(1):5-14.

Gu X, Chen ZH, Zhang SC. Fecal microbiota transplantation in childhood: past, present, and future. World J Pediatr;19(9):813-822.

van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JF, Tijssen JG, Speelman P, Dijkgraaf MG, Keller JJ. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368(5):407-15.

de Groot PF, Frissen MN, de Clercq NC, Nieuwdorp M. Fecal microbiota transplantation in metabolic syndrome: History, present and future. Gut Microbes. 2017;8(3):253-267.

Wang J, Xiao Y, Lin K, Song F, Ge T, Zhang T. Pediatric severe pseudomembranous enteritis treated with fecal microbiota transplantation in a 13-month-old infant. Biomed Rep;3(2):173-175.

de Groot PF, Frissen MN, de Clercq NC, Nieuwdorp M. Fecal microbiota transplantation in metabolic syndrome: History, present and future. Gut Microbes. 2017;8(3):253-267.

Barron, M. Fecal Microbiota Transplants (FMT): Past, Present & Future. ASM;2024

Solito A & et al. Supplementation with Bifidobacterium breve BR03 and B632 strains improved insulin sensitivity in children and adolescents with obesity in a cross-over, randomized double-blind placebo-controlled trial. Clin Nutr. 2021;40(7):4585-4594.

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