Page 5 - Introduction to FMT

FMT Introduction

Fecal microbiota transplantation (FMT) is a technique in which intestinal microbiota are transferred from a
healthy donor to the patient, with the goal being to introduce or restore a stable microbial community in
the gut. The first use of feces in such a manner was described, according to the Handbook of Emergency
Medicine, approximately 1700 years ago by a Chinese medical scientist named Ge Hong[16]. It was first
published in the English language by Eiseman et al[17] in 1958, when he reported a prompt response in
patients with antibiotic-associated diarrhea treated with fecal enemas. Nevertheless, this practice was
not well recognized until 1978, when investigators recognized Clostridium difficile infection (CDI) was the
etiology of antibiotic-associated pseudomembranous colitis[18,19]. In the past few decades, the use of
FMT for managing the increasing burdens of CDI has demonstrated it to be an effective therapeutic
strategy for CDI[20-23]. In 2012, Borody et al[24] reported that more than 1200 cases have been treated in
several centers. A total of 583 CDI patients treated with FMT produced a cumulative cure rate of more
than 90% in 36 publications[25]. In addition, standardized frozen donor fecal bacterial preparations used in
the treatment of recurrent CDI showed equal cure rates to fresh fecal samples[26]. 2013 guidelines for CDI
have recommended that FMT should be considered if there is a third recurrence after a pulsed
vancomycin regimen[27].

Although there are still many areas of uncertainty concerning this emerging technology, including
transmission of infectious organisms, long-term sequelae, and even cost-effective evaluation, the United
States Food and Drugs Administration have recently paid critical attention to FMT protocol in clinical
applications. Borody et al[24] regarded the flora in feces as a special organ, and therefore considered the
technique of FMT as a particular type of organ transplantation, regardless of the issue of immunological
rejection. FMT has hence emerged as an important therapeutic modality in the manipulation of altered
intestinal microbiota, with the indications of FMT possibly being expanded to even extra-intestinal
conditions.

RATIONALE FOR FMT

The exact mechanisms by which intestinal dysbiosis becomes involved in disease development are not
completely elucidated. Alteration of metabolic activities induced by perturbed intestinal bacterial species
leads to weakened defense of the gastrointestinal mucosa, which in turn leads to increasing intestinal
permeability and toxic substances being absorbed into the systemic circulation. Prior work has observed
disruption of the intestinal microbiota being evident at the phylum level, with marked depletion in levels
of probiotics and a relative increase in the numbers of pathogens leading to 14

Go to: complications in intestinal conditions[27]. The alteration of microbial communities in both
inflammatory bowel disease (IBD) and CDI patients was characterized by a reduction in two phyla of
bacteria, Firmicutes and Bacteroidetes, which are prominent in healthy controls[28,29]. Moreover, an
increase in Proteobacteria such as Enterobacteriaceae is also found in individuals with IBD[30].
Bacteroides fragilis, the prominent human gut commensal, can prevent and cure inflammatory disease
via the effect of its symbiosis factor (polysaccharide A, an immunomodulatory bacterial molecule) on the
activation of the Toll-like receptor 2 pathway, inducing regulatory T cells and interleukin-10
production[31]. Dextran sodium sulfate-induced colitis in a mouse model demonstrated that spore-
forming Firmicutes in clostridial clusters IV and XIVa reduced intestinal inflammation through regulatory T
cells induction[32].

FMT Introduction