Acute graft-versus-host disease (aGvHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). 1 Although aGvHD of any target organ represents morbidity, lower gastrointestinal (GI) tract involvement is complicated by high mortality. 2 Here, refractoriness to anti-GvHD therapies (eg, nonresponse to corticosteroids after 5–7 days) is associated with oneyear survival rates of less than 30%. 3, 4 So far, there has been no satisfactory improvement in patient survival with refractory GvHD. 3, 5

Loss of intestinal bacterial diversity in GvHD, both in murine models as well as in patients after allo-HSCT, was reported by Jenq and colleagues. 6 Additionally, a relative shift toward Enterococci was recently observed in GI-aGvHD after allo-HSCT, with the degree of this Enterococci-dominant dysbiosis correlating to the severity of GI-aGvHD. 7 Recent data suggest that alterations of microbial metabolites have direct salutary effects on GvHD target tissues. 7, 8 However, a causal relationship between microbial alterations and GvHD development or progression is still unproven. Fecal microbiota transplantation (FMT) aims at restoration of a physiological microbiota by transferring normal fecal microorganisms to a patient’s GI tract. 9 FMT is highly effective in Clostridium difficile infection (CDI), which is mainly mediated by the loss of the microbial colonization resistance to toxin-producing Clostridium difficile strains. 10