Fecal matter transplant

A fecal matter transplant or fecal microbiota transplant (FMT) is a therapy that involves the transfer of fecal waste from a healthy donor to the colon of a patient. It's most common use is in the treatment of recurrent clostridium difficile (C.diff) infections. Interest in fecal matter transplants has grown in those experiencing chronic gastrointestinal problems, including chronic fatigue syndrome.

Methods
Fecal matter from a person with healthy gut flora is mixed with saline, strained, inserted into the recipient patient with via a colonoscopy, endoscopy, sigmoidoscopy, or enema in order to recolonize the ill person's bowels. It is recommended that the donor be someone close to the patient, with the first choice being a spouse or significant other, but other close friends, relatives, or a "universal donor" source may be warranted. The physician should ensure that the "universal donor" source employs rigorous screening and testing standards. Testing includes screening the donors’ blood for diseases such as HIV and hepatitis and testing their stool for bacterial pathogens, giardia and cryptosporidium, parasites, and C. difficile.

Critique of Borody study using FMT for chronic fatigue syndrome
A 2012 study by Borody, at el, using a variety of antibiotics followed by one to three fecal matter transplants (and in six patients an oral course of cultured bacteria), reported a 70% rate of improvement of sleep and "lethargy/fatigue" symptoms in Fukuda CFS patients recruited from a clinic for digestive disorders. The authors reported a 58% success rate at long term followup 15-20 years post-treatment, but only 12 patients (out of the original 60) were contacted at that point. Accordingly, the long-term followup results would not have been statistically significant.

That study also neglected to use any objective outcome measurements, a control group was not included, and the symptoms used to determine a successful outcome regarding "CFS symptoms" did not account for physical limitations or many other fundamental ME/CFS symptoms. It is not clear how many symptoms were measured before and after treatment, hence it cannot be determined if any results were statistically significant. Furthermore, all patients were recruited from a clinic for digestive disorders, which would suggest that they were not typical ME/CFS patients. The recruitment criteria did not require that patients have the symptom of post-exertional malaise, hence the results may not be applicable to ME/CFS patients meeting more stringent criteria.

There was no study protocol published, and there is no explanation provided for the results first being published as a full paper fifteen years after the initial treatments took place. A conference poster abstract from 1995 indicates that other symptoms were tested at an earlier followup, but those symptoms are not reported or discussed in the 2012 long-term followup, which may indicate that the treatment was less successful than reported. The poster abstract does not appear to have been published, and the full long-term followup was published in an obscure online journal with no apparent peer review process.

This study has not been replicated, and no other studies for FMT and ME/CFS have been conducted. Accordingly, the existing evidence base in favor of this therapy is very weak.

RESTORE-ME clinical trial
A feasibility study for a clinical trial of FMT for patients with ME/CFS is in progress in the UK, with support and funding from the charity Invest in ME Research. The study is led by Simon Carding or the Quadram Institute. The RESTORE-ME clinical trial aims to find out if FMT will restore a healthy gut microbiome in ME patients, and to find out if this improves physical and mental health of those with ME. This is a double-blinded, randomized controlled trial in phase IIb, and involves 160 mildly/moderately ill ME patients. It was expected to begin in September 2020, but this has been altered due to the COVID-19 pandemic.

Risk
The U.S. Food and Drug Administration (FDA) has warned of the possiblity that FMT may cause serious or life threatening infections, including bacterial and viral infections, with at least one fatal infection reported.

Multi-drug resistant organisms
The FDA reported two cases in immunocompromised adults of bacterial infections with multi-drug resistant organisms (MDROs) that occurred due to use of investigational FMT. In both cases, the FMT was prepared from stool obtained from the same donor, and the recipients became infected with extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E.coli), which was later found to be present in donor stool. One of the recipients died. As a result of these cases, the FDA has determined that donor screening must include questions that address risk factors for MDROs and donor stools must be tested for MDROs.

SARS-CoV-2 and COVID-19
The SARS-CoV-2 RNA and/or virus that causes COVID-19 has been found in stool samples, suggesting it could be transmitted by FMT. The FDA has stated the risk is unknown and advised donor screening for SARS-CoV-2 and testing donors or donor stools be screened, and informing patients of the potential risk.

United States
FMT is regulated by the U.S. Food and Drug Administration (FDA), which has not approved it for any use. The FDA has classified human stool as a biological agent and determined that its use in fecal matter transplantation (FMT) therapy and other research should be regulated to ensure patient safety. In order for a physician or researcher to use FMT in a clinical trial or to treat any condition other than reoccurring, antibiotic-resistant clostridium difficile infections, an investigational new drug (IND) permit is required.

United Kingdom
In the UK, some clinics, such as the Taymount Clinic, Hertfordshire, England, offer FMT for a wide range of GI and chronic illnesses.

Australia
Australia has some of the most active FMT clinics, such as the Centre for Digestive Diseases in Sydney, under the direction of Thomas J. Borody, MD, PhD. Dr Borody has conducted many FMT studies over the past 30 years on FMT, including studies assessing efficacy for chronic fatigue syndrome, although criticism regarding patient selection and follow-up have caused doubt on the study results. (Critique can be found in a section below.) Additionally Dr Paul Froomes, Melbourne, performs FMT.

Norway
In 2017, the Research Council of Norway (Norges forskningsråd) announced undertaking a randomized controlled trial for use of fecal microbiota transplant in chronic fatigue syndrome.

A randomized, placebo-controlled trial called "The Comeback" study is currently underway at the University Hospital of North Norway. Eighty ME/CFS patients will be followed up for 12 months after receiving either fecal microbiota transplantation (FMT) or a placebo. The trial will take many years to complete. Final results are expected in 2023.

Home experimentation
The medical cautions and strict FDA regulation hasn't stopped people, especially those with GI illnesses, such as ulcerative colitis or irritable bowel syndrome, from experimenting on their own with FMT. Recipes for do-it-yourself FMT are abundant online, including Dr. Sarah Myhill's protocol, Probiotic Therapy Home Infusion Protocol.

Research studies

 * 2012, The GI microbiome and its role in Chronic Fatigue Syndrome: A summary of bacteriotherapy
 * 2013, High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients
 * 2016, Fecal Microbiota Transplantation and Its Usage in Neuropsychiatric Disorders
 * 2019, A retrospective outcome study of 42 patients with Chronic Fatigue Syndrome, 30 of whom had Irritable Bowel Syndrome. Half were treated with oral approaches, and half were treated with Faecal Microbiome Transplantation - (Full text)
 * 2019, Research Progress in Fecal Microbiota Transplantation as Treatment for Irritable Bowel Syndrome - (Full text)

Learn more

 * Gut Microbes, FMT and ME - slides by Simon Carding Video - RESTORE-ME study
 * FMT Clinical Trial - Invest in ME Research, Oct 8, 2019
 * Designer Shit – a documentary about FMT scheduled for release sometime in 2019
 * Home Infusion Protocol published by Sarah Myhill
 * Infectious Diseases Society of America Information about FDA regulations re: FMT
 * The Fecal Transplant Foundation
 * 24 Aug 2019, The First ME/CFS Fecal Transplant Study Suggests the Treatment Holds Promise by Cort Johnson for Simmaron Research