Although Clostridium difficile is present in the intestines of ∼3–5% of healthy adults,1 the occurrence of C. difficile infection (CDI) in healthy individuals is relatively uncommon due to the protective effect of the gut microbiota. The incidents and severity of CDI has risen significantly over the last decade, and it is now recognised as the main causative agent of healthcare-associated infectious diarrhoea in hospitals worldwide.2 The standard treatment for CDI is the administration of metronidazole for mild to moderate infections, and oral vancomycin or fidaxomicin for severe infections and relapses. The ability of C. difficile to form spores, coupled with the increase in antibiotic-resistant strains, can lead to persistence of infection, relapses, and the administration of more antibiotics, which further depletes the commensal bacteria. This creates an environment that is more favourable to C. difficile, thus setting up a cycle of relapse and re-infection. It is estimated that 20-30% of patients who develop a first episode of CDI go on to have at least one relapse, and of these, a further 60% develop further episodes of relapses.3 This increases the need for further antibiotics, the risk of antibiotic-resistance in the gut commensal flora, and costs to the health service, with each episode of CDI estimated to cost approximately £7000 in 2010.4
Faecal microbiota transplants (FMT) represents an effective alternative to antibiotics to treat recurrent CDI (rCDI), with a primary cure rate as high as 91%.5 The central tenet behind FMT is that the introduction of a healthy bacterial community into the intestines produces an environment that is less favourable to C. difficile by increasing colonisation resistance and reinstating a protective effect. The advantages of this treatment are that it is quick, cost-effective, and could help to eradicate antibiotic resistant strains of C. difficile.
It is known that a dysbiotic gut microbiota increases the risk of developing CDI, however whether there is a common element within this community composition that could help to determine if a patient is at greater risk of rCDI is as yet unknown. The reduction in diversity within the dysbiotic gut microbiota would also suggest a reduction in metabolic potential through the loss of gene diversity. The functional redundancy6 within the gut microbiota suggests, that metabolic function is more relevant than which species are present or absent. Whilst a number of studies have looked at the changes in microbiota composition due to FMT,7, 8, 9, 10 we know little about the changes to the metabolic capacities of the altered microbiota. The aim of this study was to assess FMT-induced changes in both the microbial community structure and metabolite profiles of the gut microbiomes of seven patients with rCDI, as well as those of their associated FMT donors.