Treating inflammatory bowel disease (IBD) with fecal microbiota transplant (FMT) shows potential, but longer clinical trials and more information on the best method of delivery, the risks, and the best matched donor for each patient are needed, according to a review study.
The study, “Fecal microbiota transplant — a new frontier in inflammatory bowel disease,” appeared in the Journal of Inflammatory Research.
The intestinal microbiota — the community of microorganisms in the gut — is involved in several processes, including gut development, immune responses, and resistance to pathogens, as well as brain development and function. However, changes in bacterial composition and number, known as dysbiosis, are well-known in IBD patients and are considered key in gut inflammation.
FMT, a procedure in which fecal or stool matter from a healthy donor is placed in a patient — often by colonoscopy or rectal enema — is intended to restore bacterial numbers.
It can reduce bowel permeability by boosting the production of short-chain fatty acids and correct dysbiosis by lowering the generation of inflammatory factors, inhibiting the activity of immune T-cells, and suppressing the adhesion of leukocytes, or white blood cells, to the endothelium, which lines the interior of all blood vessels.
Prior to the procedure, the stool is collected by the donor and may be used immediately or frozen for later use. It is diluted in saline or other solvents, homogenized, and filtered. The resulting solution, containing particles less than 2 millimeters wide, is then infused into the gastrointestinal (GI) tract of the patient or further processed to obtain pellets for oral administration.
Gelatin-coated or frozen capsules are being investigated for their ability to improve the therapy’s accessibility and patient compliance, according to the researchers.
Choice of delivery route depends on the type of microbiota, the patient’s overall health status, and whether the patient is being treated for ulcerative colitis (UC) — one of the main forms of IBD — or Clostridium difficile infection (CDI), for which FMT has been shown to be effective. Determining the number of required administrations is also crucial.
The selected donor must have no risk factors for transmissible diseases nor be taking medications that may affect the microbiota. Satisfaction of these requirements is typically determined by a preliminary interview, followed by a minimum of two rounds of blood and stool tests.
Initially, the donor fills out a questionnaire on exposure to HIV, syphilis, hepatitis and other conditions, use of illegal drugs, sexual behavior, recent travels, prior organ transplants, history of IBD, chronic constipation, and other chronic GI disorders, among other factors. Significant exposure to one or more risk factors makes potential donors unsuitable.
Selected donors then undergo an in-person health assessment to further describe any changes in their health, diet, and bowel habits. Stool and blood samples are analyzed for transmittable infectious diseases. Those who test positive are excluded, confidentially informed, and referred for treatment. Even for donors who are suitable, the questionnaire must be repeated and samples retested every three to six months.
Important factors to take into account are the exact composition of the donor’s microbiota, which affects the procedure’s effectiveness, and the donor-recipient microbiota compatibility. To optimize donor screening, the Microbiome Health Research Institute developed a public stool bank.
Specifically in Crohn’s, research has demonstrated that FMT led to a clinical response, with a subset of patients showing clinical remission. In addition, a study on 30 refractory (treatment-resistant) Crohn’s patients showed that FMT led to clinical improvement rates of 86.7% and remission rates of 76.7% at one month.
However, available studies lack standardized treatment protocols and routes of administration, and did not include a placebo group, which preclude definitive conclusions. To overcome these limitations, two placebo-controlled trials have been done in UC patients receiving FMT, but only one involving FMT via rectal enema reported clinical remission.
“These data highlight the fact that IBD is not a pure microbiota-driven disease such as CDI,” the team wrote. More randomized, placebo-controlled trials are warranted to clarify the potential of FMT in IBD, they say.
Adverse effects related to FMT can be short- or long-term, although they are still largely unknown due to the lack of long clinical trials. Obesity, diabetes, atherosclerosis, and colon cancer are among the proposed long-term risks of altered gut microbiota.
Short-term side effects related to the delivery method include mild fever and mild GI symptoms — such as abdominal discomfort, flatulence, or diarrhea. Depending on the route of administration, there have been reported cases of bleeding, effects related to anesthesia, and gut infection.
Regarding contraindications for FMT, patients with severe bowel disease cannot undergo colonoscopies, while the risk of enteric microbe transmission excludes patients with severe immunosuppression (immune system impairment) and decompensated liver cirrhosis.
More data on modifications to the host’s gut microbiota, metabolic mechanisms, and microbial genes in the GI tract are required, the team said. Also, “more studies are needed to assess the optimal route of administration and the frequency of FMT, the best matched donor for each patient as well as the risks associated with FMT in IBD,” they add.
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