Location affects bacterial success
Certain beneficial bacteria were found to thrive more when the donor transplant was administered to the small intestine than to the large intestine.
Of note, Lactobacillus species and Holdemanella biformis grew and then dropped off sharply after 3 months in patients who received a single-dose fecal transplant in the large intestine, while they grew after 3 months and continued to grow after 6 and 12 months in the groups who received a fecal transplant in the small intestine.
“We think bacteria in the small intestine have different characteristics to those in the large intestine,” Dr. El-Salhy said. “This is relatively new, because many years ago it was thought that bile acids prevented bacterial survival. Now we know lots can thrive in the small intestine.”
“It might be viral or some other component that is most effective here. We don’t know yet, but so far we have identified 11 bacteria of interest,” he added.
Broader questions
“Rather than focusing on a specific, single strain microbe as a predictor of success in a disease, the global equilibrium of microbiota is more important, and microbial ecology parameters would be interesting to assess,” remarked Gianluca Ianiro, MD, from the Università Cattolica del Sacro Cuore, Rome, who comoderated the session. “Selected survival of some bacteria through the gut may be the response.”
FMT emerged in response to the challenges posed by recurrent C. difficile infections, noted Alexander Khoruts, MD, a professor of medicine in the division of gastroenterology, hepatology, and nutrition at the University of Minnesota, Minneapolis, who was not involved in the research.
“It is much harder to achieve remodeling of the gut microbiome in non–C. difficile conditions where there is an intact and resilient indigenous microbiota,” he said in an interview. “Therefore, regimens using antibiotic preconditioning and repeated administrations of microbiota are generally more efficacious in achieving this objective.”
The specificity of the bacteria according to disease type targeted was important, said Dr. Khoruts, who has a special interest in gut microbiota.
“The big question in non–C. difficile indications is the composition of donor microbiota. It is critical that we understand the mechanisms involved in each target disease to design appropriate microbiota-based therapeutics,” he said.
Dr. Khoruts sounded a note of caution with respect to establishing the pharmacokinetic and dynamic data related to FMT, which is classified as a drug in the United States.
“It’s imperative that we develop the pharmacology discipline appropriate for this class of therapeutics, including their pharmacokinetics and pharmacodynamics, and an understanding of their potential toxicity and drug-drug interactions,” he said.
Drug distribution data are needed to determine host-microbiota interactions.
“This includes the small bowel microbiome, which continues to be woefully understudied,” Dr. Khoruts said.
Dr. El-Salhy reports no relevant financial relationships. Dr. Ianiro reports receiving personal fees for acting as speaker for Biocodex, Sofar, Malesci, and Tillotts Pharma, and for acting as consultant/advisor for Ferring Therapeutics, Biocodex, Tillotts Pharma, and Zambon. Dr. Khoruts reports he has patents pertaining to fecal microbiota separation from stool and their cryopreservation and lyopreservation.
A version of this article first appeared on Medscape.com.