Intestinal microbiota transfer, fecal transplantation or fecal bacteriotherapy (often abbreviated as
FMT) has only recently gained increasing popularity with its success for treating Clostridium difficile
infection in the last decade [2]. However, the use of bowel-derived (of enteric) material for treatment of
disease goes back more than 2500 years, when traditional Chinese medicine already used human fecal
suspension or infant feces given orally to treat several gastro-intestinal related illnesses, including
chronic diarrhea and food poisoning [3]. Although intestinal microbe infusions used in veterinary
practice in the Western world can be dated back to the 17th century as a treatment for ruminal acidosis
[4], application in humans took until 1958, when Eiseman described the first report on the efficacy of
fecal transplantation in the treatment of chronic (broad spectrum antibiotics induced) diarrhea [5]. The
above- mentioned therapies were given with great efficacy, but with little biological substantiation.
With the current developments in next generation culture-independent tools, such as 16S ribosomalRNA
gene sequencing, broader insights into the composition of the gut microbiota have now
rendered significant associations of intestinal microbiota composition and human (predominantly
autoimmune) disease states [6]. This is of specific interest as a number of bacteria-derived proteins have
now been identified as superantigens that can act as either B cell or T cell activators (so called molecular
mimicry) thus eliciting nonspecific activation of lymphocytes, including self-reactive lymphocytes [7].
Interindividual variations in gut microbiota might therefore lead to variations in immune activation, and
possibly directly to autoinflammatory conditions. Following Koch’s postulates to dissect causality from
correlation in human (infectious) disease [8], application of fecal transplantation in these (autoimmune)
diseases might be regarded an interesting research tool to identify causally involved intestinal microbial
species and/or non-microbial components as initiators of both gastrointestinal and systemic autoim-
mune reactions. In this review, we will thus aim to demonstrate whether specific human diseases
correlate with altered intestinal microbiota composition and increased intestinal permeability. Moreover,
we will present current (mostly case report-based) evidence on efficacy of fecal transplantation as
treatment modality in (autoimmune) diseases (also see Fig. 1). Finally, with respect to safety we will
describe optimalized screening protocol for fecal donors, way of infusion and the potential clinical
applicability of fecal transplantation.