Longitudinal study of the human gastrointestinal microbiota following fecal microbiota transplant (FMT) for Clostridium difficile infections

Abstract

BackgroundClostridium difficile infection (CDI) is a nosocomial infection known to be the most crucial antecedent of healthcare‐associated diarrhea. Fecal microbiota transplant (FMT) has emerged as a successful treatment method when standard antibiotic therapy is ineffective for refractory CDI. However, our understanding is limited regarding the longitudinal differences in the gastrointestinal (GI) microbiota between patients with a successful or failed FMT.ObjectiveWe aimed to investigate the microbial structure and predictive metagenome functional content of FMT patients over a 90‐day period, and to determine if these outcomes differed in patients with a successful or failed procedure over time.MethodsPatient microbiome samples were assessed prior to FMT (n=8), and at 30 (n=4) and 90 days (n=4) post treatment. Treatment failure was defined as ≥3 episodes of diarrhea/day or, within 30 days, retreatment with antibiotics or FMT. Metagenome functional potential was predicted using PICRUSt (v. 1.0.0). PICRUSt data and relative abundances of microbial taxa were then analyzed using LEFSe (v. 1.0), a Linear Discriminant Analysis model which evaluated discriminant features using a Kruskall‐Wallis test for FMT status (success/fail) followed by Wilcoxon test for pairwise comparisons between timepoints (baseline/30‐d/90‐d).ResultsAcross timepoints, relative abundance of Fusobacteriaceae was significantly higher among patients with a failed FMT (p=0.015), and Enterococcaceae (p=0.020) and an unclassified family of Lactobacillales (p=0.023) were significantly greater in patients with a successful FMT. At the genus level, relative abundance of Lactococcus (p=0.027) and Fusobacterium (p=0.007) were higher in patients with failed FMT over time. Metagenome functional potential analyses revealed that enzymes related to steroid hormone and glycosphingolipid synthesis and glycosaminoglycan degradation were significantly higher in participants with a failed FMT over time.ConclusionsThe use of innovative bioinformatic tools in the present study permits identification of key differences in microbial community structures and functional gene potential between participants with a successful or failed FMT procedure across a 90‐day period. Differences in steroid hormone synthesis, glucocorticoid in particular, has been linked to increased mortality of CDI patients. An increase in the synthesis and metabolism of glycoconjugates have also been associated with an increase in the pathogenicity of microbes such as C. difficile. More research is required to determine if the gut microbial structure of patients with CDI can be used to predict if FMT is the best route for treatment.Support or Funding InformationPartial funding for this study was provided by the USDA National Institute of Food and Agriculture, Hatch project ILLU 538 384.