Table of Contents
- China in the 4th century
- Western Medicine and FMT
- FMT revived in modern times
The numbers in parentheses in the text refer to the reference numbers at the bottom of the article.
China in the 1.4th century
The earliest surviving historical description of FMT (fecal microbiota transplantation) is found in a book on emergency medicine called Zhou Hou Bei Ji Fang, written by Ge Hong during the Jin Dynasty in 4th century China.
This book describes administering stool from healthy individuals “via the digestive tract” to treat symptoms such as severe diarrhea, food poisoning, fevers, and typhoid fever.
Though the description is softened by terms like “yellow soup,” drinking it orally must have been repulsive. Yet life itself was at stake. They likely drank it with the mindset that necessity knows no law.
We feel disgusted by excrement not only because it is human culture. The sensation is also a self-preservation instinct, since snot, drool, vomit, and feces may contain bacteria and viruses that can cause serious infections.
Since there was no way to know that microorganisms in stools were effective against diseases at that time, the FMT method must have started as a folk remedy that “worked when I tried it,” apart from any scientific technology or theory.
In China, since other physicians were already commonly practicing this by the time of 4th-century records, its history may be even older.
Did they get the idea by observing other animals eating their own feces? One can only marvel at the power of ancient people to leap beyond conventional reasoning.
A similar description is found in the 16th century, also in a Chinese medical book. There is a paper (1) that describes the history of this area in great detail, and anyone interested should read it.
China was not the only culture that cured disease by ingesting stool.
During World War II, Nazi German soldiers discovered that Arab nomads cured dysentery by eating camel dung. Whenever the nomads had even the slightest bit of diarrhea, they would follow the camels and eat the freshly defecated feces (2, p. 208).
Science later proved that warm camel dung contained large amounts of Bacillus subtilis, a bacterium that destroyed viruses and bacteria in the intestines in a state of diarrhea (3).
These facts show that FMT is not the product of science and technology, but of folk medicine. Modern science is merely trying to elevate this method to a medical treatment that can be used in non-emergencies by making it safer and more effective.
2. Western medicine and FMT
The first time FMT appeared in Western medicine as a paper (4) was in 1958.
Doctors at the Denver Veterans Administration Hospital administered stool samples from healthy individuals anally to four patients suffering from a deadly form of diarrhea called pseudomembranous colitis. The disease is mostly what we now call Clostridioides difficile [C. difficile] enteritis. (formerly known as Clostridium difficile).
The results were remarkable: all four patients recovered rapidly.
Doctors attempted to advance this treatment to the stage of full-scale clinical trials, but ultimately failed.
It was the era of antibiotics. Alexander Fleming discovered penicillin in 1929, and during World War II, many wounded soldiers escaped fatal infections thanks to antibiotics.
When Fleming was awarded the Nobel Prize in Physiology or Medicine in 1945 and antibiotics became available to the general public, they were also administered for non-fatal infections.
Bacteria are the enemy. And mankind has won the battle.
What people had at the time was such an aversion and exuberance for germs that the “dirty and dangerous” FMT, which contained large amounts of bacteria and viruses, was not widespread at all and was forgotten.
3. FMT revived in the modern age
For a long time afterward, FMT remained a treatment in the shadows.
It was only performed sparingly as a last resort when antibiotics failed and lives were at risk. We can only express our gratitude to the doctors (5,6) who kept the flame of FMT alive over the past half-century.
At the risk of being too forward, one of the founders of our affiliate, the Intestinal Flora Transplant Clinical Research Foundation, a clinical laboratory technician, has been performing FMT in Japan for about 40 years with the cooperation of physicians and has worked hard to improve the methodology.
As a result, he has succeeded in developing a more effective method of implementation called NanoGAS® FMT.
In the 2000s, C. difficile enteritis (CDI) became a serious social problem in the United States. Due to overuse of antibiotics and other factors, only one type of bacteria overruns the intestinal ecosystem, resulting in severe diarrhea, weight loss, and in the worst cases, death.
In the United States alone, 500,000 people are affected each year and 30,000 die (7).
The treatment began to gain attention as some physicians, aware of the dramatic effects of FMT on this disease, began to perform it on an increasing number of their patients as a last resort.
The timing was good, as the importance of symbiotic microorganisms such as commensal bacteria was just beginning to be recognized with the launch of the Human Microbiome Project.
In 2012, Hamilton et al. (8) from the United States showed similar efficacy in frozen feces, and in 2013, van Nood et al. (9) from the Netherlands demonstrated the efficacy of FMT in a randomized controlled trial for recurrent CDI.
This randomized controlled trial was an important accomplishment that made a major leap forward in moving FMT therapies from the position of folk medicine to that of modern science-based medicine.
It was proven that FMT did not work by chance or placebo effect, on the contrary, it worked so well that it became unethical to conduct any more comparative studies, and the study was terminated with the results of the first 43 patients out of the planned 120 patients. The study was terminated after the results of the first 43 patients out of 120 planned.
Because the cure rate for FMT was 94% and the standard of care ranged from 23% to 31%, the medical safety committee, the supervising body, agreed to stop the trial and make FMT the new standard of care.
Thus, FMT was welcomed into modern medicine with its overwhelming effectiveness, without any specific mechanism being elucidated.
Nevertheless, many challenges still remain.
How should safety be ensured?
What are the criteria for donor selection?
Are there other indications for the disease?
Could this be done in a more convenient way?
And it is also of interest to researchers to elucidate why and how this method works.
1. Zhang F, Cui B, He X, Nie Y, Wu K, Fan D. Microbiota transplantation: concept, methodology and strategy for its modernization. Protein Cell. 2018;9(5):462-473. doi:10.1007/s13238-018-0541-8
2. Rob Desalle, Perkins Susan L. The World of the Microbiome–Trillions of Microbes in, on, and around You. Kinokuniya Publishing Co.; 2016.
3. Damman CJ, Miller SI, Surawicz CM, Zisman TL. The microbiome and inflammatory bowel disease: is there a therapeutic role for fecal microbiota transplantation? Am J Gastroenterol. 2012;107(10):1452-1459. doi:10.1038/ajg.2012.93
4. Eiseman B, Silen W, Bascom GS, Kauvar AJ. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery. 1958;44(5):854-859.
5. Bennet JD, Brinkman M. Treatment of ulcerative colitis by implantation of normal colonic flora. Lancet Lond Engl. 1989;1(8630):164. doi:10.1016/s0140-6736(89)91183-5
6. Borody TJ, George L, Andrews P, et al. Bowel-flora alteration: a potential cure for inflammatory bowel disease and irritable bowel syndrome? Med J Aust. 1989;150(10):604. doi:10.5694/j.1326-5377.1989.tb136704.x
7. Feuerstadt P, Theriault N, Tillotson G. The burden of CDI in the United States: a multifactorial challenge. BMC Infect Dis. 2023;23(1):132. doi:10.1186/s12879-023-08096-0
8. Hamilton MJ, Weingarden AR, Sadowsky MJ, Khoruts A. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012;107(5):761-767. doi:10.1038/ajg.2011.482
9. van Nood Els, Vrieze Anne, Nieuwdorp Max, et al. Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile. N Engl J Med. 2013;368(5):407-415. doi:10.1056/NEJMoa1205037
