To ensure safety, the U.S. Food and Drug Administration (FDA) requires that clinical trials using FMT be conducted based on an Investigative New Drug (IND) application. In Japan, a single-arm validation study is underway to determine whether FMT can be covered by insurance under Advanced Medical Treatment B for Clostridioides difficile infection starting in 2020. Other countries have also begun discussions on the regulation of FMT.

Serious adverse events due to FMT are addressed in the “Report on Bacterial Products Based on Microbiome Research” from the Pharmaceuticals and Medical Devices Agency. The following is based on it.
No serious adverse events have been reported in Japan; however, two serious adverse events (one death and one recovery) were reported in the United States in 2019.

In March 2019, two patients at Massachusetts General Hospital (MGH) who received FMT oral capsules of the same donor origin that were produced in the hospital became infected with ESBLs (extended spectrum beta-lactamases) producing organisms. One patient received FMT to treat hepatic encephalopathy due to hepatitis C. The ESBL-producing bacteria infection was detected and the patient recovered with antimicrobial therapy. Another patient undergoing hematopoietic stem cell transplantation to treat myelodysplastic syndrome (after cyclophosphamide and mycophenolate mofetil) underwent FMT to prevent graft-versus-host disease (GVHD). The FDA promptly issued an alert and halted the provision of FMT nationwide.
An investigation into the cause revealed that MGH had not performed ESBL testing as required by FDA guidelines and that the donor stool was contaminated with ESBL-producing bacteria. Three months after the alert, the IND study using FMT was resumed with a recommendation for thorough ESBL testing.
In addition, in 2020, six serious adverse events (all of whom recovered) were reported; the FDA issued an alert for this event as an adverse event caused by enteropathogenic E. coli and Shiga toxin-producing E. coli based on donor stool.

Thus, the most important safety consideration for FMT is its potential to cause serious infections. For example, COVID-19 was noted early in the pandemic as a potential source of infection, as the virus was detected in stools; the FDA issued a safety alert in March 2020 to prohibit the use of FMT in stools acquired on or after December 1, 2019 and requested COVID-19 transmission prevention measures (testing of donors for infection and obtaining additional consent from recipients) when providing FMT stool juice using stool obtained on or after December 1, 2019.
Infectious disease tests that should be considered, as suggested by FDA in its review on FMT, include tests for pathogenic bacteria, fungi, viruses, and parasites, but in our country, tests for hepatitis E, hepatitis E virus, etc. should also be considered.

Fecal microbiota transplantation is currently being studied at various institutions in Japan and abroad, and has shown some efficacy in the treatment of ulcerative colitis and irritable bowel syndrome. However, in Japan, it has not yet been subject to the Clinical Research Act, so the final evaluation has not yet been made, and the full amount of the treatment must be borne by the patient.
The following is a summary of the history of the usefulness of gut flora in Japan and abroad to date. New information will be posted on this site’s blog as it becomes available.

The oldest origin of fecal microbiota transplantation is said to be around the 4th century in China, when a person suffering from diarrhea who was unable to stop it was cured of it by placing a healthy person’s stool in the buttocks of the person. Since then, research on fecal microbiota transplantation has progressed in Western countries, starting with a report on pseudomembranous enteritis in 1958.

Fecal microbiota transplantation came back into the spotlight in 2013, when a study in the Netherlands showed that it was effective in treating Clostridium difficile infections (CDI), which are caused by the use of high doses of antibiotics in surgical procedures and other procedures that result in antibiotic resistance. This causes a loss of diversity in the intestinal microflora, which should normally contain thousands of species, and in the worst case, the disease is said to be fatal. More than 500,000 people in the United States are affected by this disease each year, and 30,000 people die each year.

The following year, in 2014, the U.S. Food and Drug Administration (FDA) positioned “fecal microbiota transplantation as the first-line treatment of choice when CDI is multidrug-resistant,” and its effectiveness is being medically proven.
On the other hand, in 2019, the FDA issued a warning that “fecal microbiota transplants may pose a serious infection risk,” referring to a case in which a lethal organism was transplanted without proper screening at the time of transplantation, resulting in a death.

As of 2021, fecal microbiota transplantations exist under the FDA’s executive discretion policy and can be used to treat CDI. However, it is difficult to obtain the benefits of this new therapy without the provision of a reliable source of bacteria and the selection of a specialized hospital that can provide accountability.

Research on fecal microbiota transplantation in Japan began in 2013 at eight university hospitals and other facilities around Japan, with clinical trials focusing on ulcerative colitis and Crohn’s disease (the first phase was completed in 2016), and the effects on inflammatory bowel disease are being reported one by one.

A list of affiliated medical institutions that have the correct knowledge, optimal screening, and superior medical technology to treat these diseases can be found here.