Reset of a critically disturbed microbial ecosystem: faecal transplant in recurrent Clostridium difficile infection

Abstract

Recurrent Clostridium difficile infection (CDI) can be effectively treated by infusion of a healthy donor faeces suspension. However, it is unclear what factors determine treatment efficacy. By using a phylogenetic microarray platform, we assessed composition, diversity and dynamics of faecal microbiota before, after and during follow-up of the transplantation from a healthy donor to different patients, to elucidate the mechanism of action of faecal infusion. Global composition and network analysis of the microbiota was performed in faecal samples from nine patients with recurrent CDI. Analyses were performed before and after duodenal donor faeces infusion, and during a follow-up of 10 weeks. The microbiota data were compared with that of the healthy donors. All patients successfully recovered. Their intestinal microbiota changed from a low-diversity diseased state, dominated by Proteobacteria and Bacilli, to a more diverse ecosystem resembling that of healthy donors, dominated by Bacteroidetes and Clostridium groups, including butyrate-producing bacteria. We identified specific multi-species networks and signature microbial groups that were either depleted or restored as a result of the treatment. The changes persisted over time.Comprehensive and deep analyses of the microbiota of patients before and after treatment exposed a therapeutic reset from a diseased state towards a healthy profile. The identification of microbial groups that constitute a niche for C. difficile overgrowth, as well as those driving the reinstallation of a healthy intestinal microbiota, could contribute to the development of biomarkers predicting recurrence and treatment outcome, identifying an optimal microbiota composition that could lead to targeted treatment strategies.

Discordant temporal development of bacterial phyla and the emergence of core in the fecal microbiota of young children

“…However, the microbiota similarities, both in short and long term, were still remarkably lower than previously observed for western adults by using the same microarray technique for microbiota assessment (JalankaTuovinen et al, 2011;Rajilić-Stojanović et al, 2013;Fuentes et al, 2014;Satokari et al, 2014). Furthermore, we found that the most predominant Figure 6 The development of core microbiota # .…”

Dynamics of an experimental microbial invasion

“…Invasions from pathogenic microbes have been relatively wellstudied because they are comparatively easy to track, in part, due to strong, observable impacts (1). A particularly well-studied example is the invasion of the human gut microbiota by pathogenic bacteria (6,7). We know, however, much less about invasion by nonpathogenic microbes, even though we have evidence that they do occur in nature.…”

Biome engineering‐2020

“…Clostridium difficile decreased from initial 4% to 0.2% after FMT. The low microbiota diversity in the patients increased to the diversity of the donors within 2 weeks (van Nood et al ., 2013; Fuentes et al ., 2014). A recent trial reproduced an 84% cure rate with faecal transplantation given as enema to 232 Canadian CDI patients, who were after intensive antibiotic pretreatment randomized to either fresh or frozen stool preparations, without difference in cure rate (Lee et al ., 2016).…”