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By: Anu Shrestha

Anu ShresthaI first heard about this icky procedure, the fecal material transplant (FMT) in 2013. It is icky, but at the same time very interesting, and the possibilities are limitless.

FMT involves taking a donor’s feces and placing them inside the colon of the patient. The concept of using fecal matter as medicine is not new. Fecal suspensions to treat food poisoning and severe diarrhea were first reported in fourth century by a Chinese doctor named Ge Hong. This old technique has gained new momentum since Max Nieuwdorp and his supervisor used this procedure to cure an 81 year old-woman who suffered from complications of urinary tract. The antibiotics wiped-out normal gut flora (good bacteria) allowing the opportunistic bacteria, Clostridium difficile, to flourish, causing terrible diarrhea and bowel inflammation. According to the Centers for Disease Control and Prevention, C. difficile was estimated to cause almost half a million infections in United States in 2011, and 29,000 died within 30 days of the initial diagnosis.

capsuleThe human gut microbiome has been described as a “virtual organ.” Conditions ranging from inflammatory bowel diseases to obesity to asthma and cancer have been linked to gut flora. It makes sense to use FMT to replenish normal gut flora that are wiped out by repeated use of antibiotics to fight infection or the use of conventional chemotherapy such as an alkylating agent, anthracyclines, antimetabolites to fight cancer. Replenishing the gut flora to its optimum level would mitigate side effects of medicines as well as treat some diseases.

Fecal microbiota transplantation by pill reduces both the procedural costs and risks associated with the invasive delivery methods, such as naso-duodenal tube or through colonoscope. In October 2015, OpenBiome, a team from Harvard and MIT, created the FMT capsule, and they have provided over 7,000 treatments to more than 450 clinical partners across six countries and supported 10 clinical studies.

Currently, the recommended dose of an FMT capsule G3 for treatment of recurrent C. difficile is 30 capsules, swallowed in a single session. Capsules are size 00, approximately the size of a large multivitamin, and capsules should be kept frozen until the time of administration.

Now, here lies an opportunity to develop formulations for FMT that are the most convenient and cost effective for patients, doctors, and the whole health care system. An elderly patient having to swallow size 00 capsules 30 times is terrifying. The storage condition required for capsules G3 pose a hurdle in distribution. To solve these problems, efficient enteric coated capsules (1 or 2 capsules of size 2/3 ) that are able to withstand room temperature environment for a prolonged period of time would be ideal. Developing enteric coated capsules/tablets through a new formulation system can offer patients comfort and improve logistic burden.

The other possibility is to isolate the different bacterial strains and identify each species from fecal microbiota in order to cultivate in laboratory. Combining all of the bacterial species in proper proportion and capsulated in enteric coated capsule would provide approaches to move away from icky material.

Anu Shrestha, B.PH., M.S., is a pharmaceutical professional working in design and development of pharmaceutical products, including formulation, scale-up, and tech-transfer of small molecule commercial products.