32 7.6 – Potential Future Directions

The Use of Controls

Controls are crucial to any study and will allow the comparison in efficacy between the FMT treatment and no treatment. A negative control can be the use of a purified fecal sample absent of any microbiota to ensure that there would be no hidden factors affecting the progression of CD. A positive control can be the use of feces from a previous donor that has participated in another FMT study with recognized remission results as a method of ensuring that the fresh fecal microbiota used in this study has been successfully extracted and transplanted.

A Less Invasive and More Personalized Method 

Different routes of administration that can be less invasive, more convenient to the patients and as efficient as the traditional FMT includes: colonoscopy, nasogastric tube, or oral capsules. A route of administration may work for some patients, may not work for other patients. To solve this dilemma, personalized medicine can be used.

Extraction and purification of microbial bacteria from the feces to colonize the gut using capsules can be a potential method. GenFMTer can be used to automate fecal microbiota purification. Once the fetal microbiota is purified, it must be placed in a capsule. The capsule is required to be dissolved at the right time and location for each individual patient. The capsule must dissolve and release the fecal microbiota prior to reaching the ileum if the patient has ileal CD inflammation. Patients who have inflammatory masses elsewhere such as: the ascending, descending, or sigmoid colon must have the capsule dissolved accordingly. The thickness and pH dependency of the capsule material must be accurate or else the capsule will dissolve in the wrong location and time. If the capsule thickness is too thin or too thick, the microbiota will not be established in the appropriate location of the digestive tract. The pH of the small intestine compared to the large intestine slightly differs, and if the pH of the capsule is slightly off, there may not be a successful colonization. Furthermore, the capsule itself cannot cause adverse reactions or effects to the patient.

Standardization of the FMT Protocol

Standardizing FMT procedures can be difficult because DNA extraction protocols can vary between studies. Collection, transportation, handling and storage of the fecal microbiota can introduce significant changes or loss in the composition of the microbiota (Zymo Research 2018). The most variability lies within the DNA extraction protocol because there are different types of bacteria with variable cellular structure, and size (Zymo Research 2018). Lysis methods that may work for some bacteria, may not work for other types of bacteria, resulting in underrepresentation of certain species (Zymo Research 2018). These variabilities are tedious to deal with and problematic to get rid of.

Zymo Research suggested a way to standardize the FMT protocol would be to use one sequencing program to get consistent results for sequencing and classifying bacteria across different studies and labs (Zymo Research 2018).