Microbiota dynamics in patients treated with fecal microbiota transplantation for recurrent Clostridium difficile infection

Clostridium difficile causes antibiotic-associated diarrhea and pseudomembraneous colitis and is responsible for a large and increasing fraction of hospital-acquired infections. Fecal microbiota transplantation (FMT) as an alternative treatment option for recurrent C. difficile infection (RCDI) has recently been discussed favorably in the clinical and scientific communities and is receiving increasing public attention. However, short- and long-term health consequences of FMT remain a concern, as the effects of the transplanted microbiota on the patient remain unknown. While patients are generally reported to be free of RCDI-associated symptoms within a few days after FMT, they remain susceptible to relapse after additional antibiotic treatment. To shed light on associated microbial events, we performed fecal microbiota analysis by 16S rRNA gene amplicon pyrosequencing of 14 pairs of healthy donors and RCDI patients treated successfully by FMT. Simultaneous longitudinal sampling of post-FMT patients and healthy donors until up to one year after FMT, including one post-FMT patient who experienced a relapse after antibiotic treatment, allowed us not only to confirm prior reports that RCDI is associated with reduced diversity and compositional changes in the fecal microbiota, but also to characterize previously undocumented post-FMT microbiota dynamics. The taxonomic groups found increased in individual RCDI patient samples differed when compared to healthy patient samples, and included Streptococcaceae, Enterococcaceae, Enterobacteriaceae. Bacteria predicted to be involved in butyrate production (Lachnospiraceae, Ruminococcaceae) were almost uniformly reduced in RCDI patients. Interestingly, the fecal RCDI sample from the relapsing post-FMT patient showed similarities to healthy donor samples, suggesting that the microbiota phenotypes described in other RCDI patients are not sufficient to explain the disease. Moreover, overall microbiota compositions and specifically abundances of the above-mentioned Firmicutes, continued to change in asymptomatic patients for at least 16 weeks after FMT, potentially explaining the increased risk for relapse in post-FMT RCDI patients.