What are poop transplants, and how do they work?

Microbes’ friends, not enemies! Microorganisms, also known as microbes[1], are often referred to as “germs” or “bugs.” Despite the negative connotations associated with these terms, many of these organisms are beneficial and contribute to maintaining good health. Although invisible to the naked eye, microbes are ubiquitous present in the air, on surfaces, in soil, and on and inside the human body. The majority of microbes are harmless or even beneficial, including bacteria, archaea, protists, fungi, and viruses, collectively referred to as microbiota[2] [1]. After birth, humans acquire microbes from both their mothers and their surrounding environments [2]. The majority of these microbes reside in the gut, with bacteria being the most prevalent. These gut bacteria play a crucial role in aiding digestion, absorbing essential vitamins and nutrients, safeguarding our bodies against pathogens, and educating our immune systems to prevent allergies, asthma, and other immune-related disorders. Furthermore, gut bacteria can communicate with our brains, influencing our emotions and behaviors [3]. Healthy vs. Unhealthy microbiota What is a healthy gut microbiota? “Each person has a unique microbiota, and there is no one-size-fits-all definition for what comprises a healthy gut ecosystem [4]”. Although the exact appearance of a healthy microbiota remains unknown to us, we can quickly identify an unhealthy microbiota. Consuming spoiled food, for instance, can introduce harmful pathogens into the gut, resulting in an upset stomach and diarrhea. Many of us have used antibiotics[3] at some point to eliminate bacteria that cause illness. Nevertheless, antibiotics are unable to distinguish between beneficial and harmful microbes. With each antibiotic course, our gut is affected as if it were being scorched by a fire, disrupting our internal ecosystem[4]. Similar to a forest recovering after a fire, the gut microbiome typically recovers following antibiotic treatment. However, there are instances when weed-like microbes dominate instead of recovering, leading to disease, and hindering the return of beneficial microbes. Deadly Clostridioides difficile infections Clostridioides difficile[5], also known as C. difficile, is a microbe that resembles a weed and is classified as an opportunistic pathogen[6]. Opportunistic gut pathogens are microbes that typically do not cause harm, but when the gut ecosystem is compromised, these bacteria can invade and cause issues. For instance, C. difficile can reside in a healthy individual’s gut without causing any problems, thanks to the resident gut microbiota that prevents it from producing toxins and causing an infection. However, when the gut ecology is disrupted, such as after a course of antibiotics, this weed-like pathogen can take over and result in severe diarrhea [5]. According to a 2011 report by the Center for Disease Control (CDC), C. difficile is responsible for approximately 500,000 infections and causes the death of around 15,000 individuals each year in the United States. This makes it one of the most significant diseases on the CDC’s list of preventable illnesses. C. difficile tends to infect older adults with weakened immune systems or individuals who have recently been ill or taken antibiotics. Approximately 70% of C. difficile infections can be effectively treated with the antibiotic vancomycin. However, in 20-35% of cases, the infection returns after vancomycin treatment [6]. These recurrent C. difficile infections are highly resistant to further antibiotic treatment, leading to a never-ending cycle of antibiotic use and infection recurrence, which can ultimately result in the death of the patient [7]. Poop transplants Considering our forest analogy, let’s imagine a situation where a fire has devastated the ecosystem, causing the loss of its original plants and the growth of unwanted weeds. To restore the forest to its former beauty, one approach would involve removing all the weeds and introducing plants and animals from a nearby unaffected forest area. Similarly, fecal microbiota transplants (FMTs)[7], also known as poop transplants, work on a similar principle. Initially, a patient is given antibiotics to reduce the presence of C. difficile, followed by the introduction of healthy fecal matter from a donor. In the past, these transplants were done through enemas or tubes inserted through the nose and into the gastrointestinal tract. However, advancements now allow patients to take pills containing frozen or freeze-dried fecal matter. Although we don’t fully understand the exact mechanisms, the transplanted microbiota from a healthy person’s gut regain control over the ecosystem and replace C. difficile. FMTs can be either autologous, using the patient’s healthy fecal matter collected before they got sick, or heterologous, using fecal matter from another healthy individual. Despite their unappealing nature, these poop transplants have shown an impressive success rate of 80-90% in treating recurrent C. difficile infections and have helped thousands of patients in the United States. Therefore, FMT is a life-saving option for people suffering from recurrent C. difficile. FMT: the current best option for recurrent C. difficile Despite its success, FMT (Fecal Microbiota Transplantation) continues to be a treatment that sparks controversy. The reason behind this is that the composition of fecal matter can vary significantly between donors, and it cannot be controlled or regulated to the same extent as other drugs approved by the FDA. To address this issue, numerous biotechnology companies are engaged in a race to create artificial microbial communities that can be consistently manufactured under strict conditions. These synthetic communities aim to replicate the beneficial effects of natural human feces in treating recurrent C. difficile infections. However, none of these alternatives to FMTs have yet demonstrated the same level of effectiveness. The main challenge in developing an alternative lies in our limited understanding of how FMTs actually work. Although there is hope for a more superficial treatment in the future, currently, FMTs remain the best option for combating the severe problem of recurrent C. difficile infections [8].     References

1. Goffau, M. C. de, Lager, S., Sovio, U., Gaccioli, F., Cook, E., Peacock, S. J., et al. 2019. The human placenta has no microbiome but can contain potential pathogens. Nature 572:329–34. Doi: 10.1038/s41586-019-1451-5
2. Rodríguez, J. M., Murphy, K., Stanton, C., Ross, R. P., Kober, O. I., Juge, N., et al. 2015. The composition of the gut microbiota throughout life, with an emphasis on early life. Ecol. Health Dis. 26:26050. Doi: 10.3402/mehd.v26.26050
3. Johnson, K. V. A., and Foster, K. R. 2018. Why does the microbiome affect behavior? Rev. Microbiol. 16:647–55. Doi: 10.1038/s41579-018-0014-3
4. McBurney, M. I., Davis, C., Fraser, C. M., Schneeman, B. O., Huttenhower, C., Verbeke, K., et al. Establishing what constitutes a healthy human gut microbiome: state of the science, regulatory considerations, and future directions. Nutr. 149:1882–95. Doi: 10.1093/jn/nxz154
5. 2016. CDC Press Releases. Available online at: https://www.cdc.gov/media/releases/2015/p0225-clostridium-difficile.html (accessed October 31, 2019).
6. Hopkins, R. J., and Wilson, R. B. 2018. Treatment of recurrent Clostridium difficile colitis: a narrative review. Rep. 6:21–8. Doi: 10.1093/gastro/ gox041
7. Ofosu, A. 2016. Clostridium difficile infection: a review of current and emerging therapies. Gastroenterol. Q. Publ. Hell. Soc. Gastroenterol. 29:147–54. Doi: 10.20524/aog.2016.0006
8. DeFilipp, Z., Bloom, P. P., Torres Soto, M., Mansour, M. K., Sater, M. R. A., Huntley, M. H., et al. 2019. Drug-resistant coli bacteremia transmitted by fecal microbiota transplant. N. Engl. J. Med. 381:2043–50. Doi: 10.1056/NEJMoa19 10437

[1] Microbe: A microscopic organism. [2] Microbiota: All the microbes that live in and on your body. [3] Antibiotics: Medicines that kill or inhibit the growth of bacteria. [4] Ecosystem: complex and interconnected community of microorganisms residing in the human gut. [5] Clostridioides difficile: An opportunistic bacterial pathogen that causes severe diarrhea in nearly 500,000 people and is responsible for over 10,000 deaths each year in the U.S. [6] Opportunistic Pathogen: A microbe that is usually harmless but can cause disease when the immune system is depleted or when the normal ecology of the microbiota is damaged. [7] Fecal Microbiota Transplant (FMT): A procedure in which poop from a healthy donor is transplanted into the colon of a sick patient.