Fecal Microbiota Transplant: Benefits and Risks

We commend the authors of “Weight Gain After Fecal Microbiota Transplantation” for describing this case of obesity after a fecal microbiota transplant (FMT). Fecal microbiota transplant is a highly effective therapy for recurrent Clostridium difficile infection (r-CDI), and the authors discuss possible unintended consequences in a patient after successful FMT, which could be due to alteration of the gut microbiota. Strengths of this study include (1) detailed information about the clinical course of the patient receiving FMT for r-CDI and (2) characteristics of the FMT donor, the patient’s daughter. This experience led to a change in FMT donor policy at the authors’ institution. The authors do not identify the mechanism for transmission of the obese phenotype, directly demonstrate a causal relationship, or study the patient’s microbiome over time. They do identify several factors that may have contributed to weight gain after FMT in the patient. These include, but are not limited to, resolution of CDI, antibiotic use, treatment for Helicobacter pylori infection, stress related to illness, older age, and genetic factors. There is no discussion of eating patterns or changes in eating patterns in these related and presumably cohabitating individuals. These possibilities aside, there is a growing body of data exploring the relationship between host body mass index (BMI), host metabolism, and the gut microbiota. The transmission of an obese phenotype after therapeutic FMT for r-CDI has not been reported previously, to our knowledge. There are differences in the gut microbial structure between lean and obese individuals [1]. A complex relationship exists between BMI and gut microbes, and this association cannot be reduced to a correlation between specific bacterial taxonomic groups and host BMI [2, 3]. Studies of the gut microbiome in monozygotic twins with discordant BMIs have advanced the knowledge of the gut microbe-host BMI interaction by demonstrating transmissibility and reversibility of the obese phenotype. In studies by Ridaura et al [4], germ-free mice receiving a stool lavage from an obese twin developed significantly greater adiposity than mice infused with the lean twin’s microbiota, and this effect was lessened when the 2 groups were cohoused (mice are normally coprophagic). The expression of microbial genes important for detoxification and stress responses were more prominent in germ-free mice that received the obese twin microbiome compared with the lean twin flora [4]. There is also new evidence that host genetics influence the structure of the gut microbiota, and in a study of more than 400 twin pairs, specific bacterial taxa were found to be more “heritable” than others [5]. It is possible and perhaps even likely that the weight gain in the case reported was influenced not only by microbial communities transmitted during FMT, but also by genetic factors common to the FMT donor and recipient. In controlled, randomized, and doubleblinded human studies described by Vrieze et al [6], transfer of a leanmicrobiota to individuals with metabolic syndrome was associated with improved insulin sensitivity when compared with controls (individuals with metabolic syndrome who received an infusion of their own stool). In this study, butyrate-producing bacterial strains (known to activate intestinal gluconeogenesis) were increased in both lean stool samples and lean individual’s intestinal biopsies [6]. Animal studies have shown that a relative paucity of butyrate-producing bacteria in the gut is associated with increased insulin resistance, and butyrate supplementation can reverse insulin resistance in diet-induced obesity in mice [7, 8]. A reduction in butyrate-producing bacteria can be achieved using antimicrobial agents directed at Gram-positive organisms, and by this mechanism, a loss of butyrate-producing organisms has been suggested as an explanation for the increase in BMI observed in patients treated with vancomycin for treatment of infective endocarditis [9, 10]. Bacterial products from the gut have been shown to enter the serum and affect distal organs. A recent murine study showed that manipulating gut flora in germ-free maternal mice affected the Received 22 December 2014; accepted 14 January 2015. Correspondencer: Ana A. Weil, MD, MPH, Infectious Diseases, Massachusetts General Hospital, 55 Fruit St., GRJ 520, Boston, MA 02114 (aweil@partners.org). Open Forum Infectious Diseases © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of thework, in anymedium, provided theoriginalwork is not altered or transformed in anyway, and that thework is properly cited. For commercial re-use, please contact journals.permissions@oup. com. DOI: 10.1093/ofid/ofv005