Page 17 - Introduction to FMT

FMT Introduction

Insulin Sensitivity Transferred from Donors to Recipients

Recent studies in animal models show a functional relationship between the gut microbiome and obesity
and its associated metabolic disturbances. For example, obesity and insulin resistance in adult rats on a
high-fructose diet was reversed with orally administered antibiotics or oral FMT from control rats [13].
Transplanting fecal matter from twins discordant for obesity into germ-free mice was recently examined
[35]. Mice populated with the microbiome from the obese twin had increased adiposity and decreased
bacterial diversity compared to mice populated with the microbiome from the lean twin. These results
demonstrate the ability of the microbiome to alter the metabolic phenotype of the host.

To date there has only been one published study testing the efficacy of FMT specifically for treatment of
metabolic disorders in humans. The hallmark characteristic of metabolic syndrome is insulin resistance,
where cells are hypo-responsive to insulin and therefore cannot maintain glucose homeostasis. Fecal
microbiota from healthy, lean donors transferred through a duodenal tube to obese individuals diagnosed
with T2D affected host metabolism [12]. The study compared patients who received allogenic transplant
(n = 9) (i.e. stool from a healthy donor) to autologous transplantation (n =

Go to: 9) (i.e., their own stool). Although there was no reported difference in body mass index six weeks
after transplantation, there was a significant increase in insulin sensitivity (as measured by the median
rate of glucose disappearance) and fecal microbiota diversity, and decrease in fecal SCFA in the
allogenic versus autologous group. These promising results have been widely cited and inspired multiple
clinical trials (discussed below). Although FMT can induce microbiome alteration towards the donor
population for up to 24 weeks post-FMT [29], further studies are need to determine whether FMT can have
long-term effects on insulin sensitivity or weight.

Additional clinical trials are necessary to validate the effects of FMT in those with obesity or metabolic
syndrome. Importantly, these studies should be randomized, include autologous controls, contain
meticulous metadata and track long-term microbiome and patient outcome data. ClinicalTrials.gov lists
four ongoing clinical trials testing FMT for metabolic syndrome treatment. A phase 2 clinical trial at
Massachusetts General Hospital is evaluating the impact of FMT capsules on a primary outcome of body
weight reduction over 18 weeks [ClinicalTrials.gov ID NCT02530385]. An Italian phase 3 clinical trial is
tracking glucose homeostasis over a 6-month period following FMT in combination with diet and exercise
[ClinicalTrials.gov ID NCT02050607]. Researchers from China’s Nanjing Medical University are evaluating
the results of a phase 3 clinical trial on a single, nasogastric- delivered FMT on T2D over a two-year
period [ClinicalTrials.gov ID NCT01790711]. A Canadian double-blind pilot study is testing FMT efficacy in
both metabolic syndrome and non-alcoholic fatty liver disease, which is closely associated with obesity
[ClinicalTrials.gov ID NCT02496390].

The results from these clinical trials should give us a better idea of the microbiome’s functional role in
human metabolic disorder. Future studies must be designed to identify which bacterial populations or
functional microbe-host relationships underlie this phenomenon.

Super-Donors

FMT Introduction