Changes in microbial ecology after fecal microbiota transplantation for recurrent C. difficile infection affected by underlying inflammatory bowel disease

Abstract

Background: Gut microbiota play a key role in maintaining homeostasis in the human gut. Alterations in the gut microbial ecosystem predispose to Clostridium difficile infection (CDI) and gut inflammatory disorders such as inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) from a healthy donor can restore gut microbial diversity and pathogen colonization resistance; consequently, it is now being investigated for its ability to improve inflammatory gut conditions such as IBD. In this study, we investigated changes in gut microbiota following FMT in 38 patients with CDI with or without underlying IBD.

Results: There was a significant change in gut microbial composition towards the donor microbiota and an overall increase in microbial diversity consistent with previous studies after FMT. FMT was successful in treating CDI using a diverse set of donors, and varying degrees of donor stool engraftment suggesting that donor type and degree of engraftment are not drivers of a successful FMT treatment of CDI. However, patients with underlying IBD experienced an increased number of CDI relapses (during a 24-month follow-up) and a decreased growth of new taxa, as compared to the subjects without IBD. Moreover, the need for IBD therapy did not change following FMT. These results underscore the importance of the existing gut microbial landscape as a decisive factor to successfully treat CDI and potentially for improvement of the underlying pathophysiology in IBD.

Conclusions: FMT leads to a significant change in microbial diversity in patients with recurrent CDI and complete resolution of symptoms. Stool donor type (related or unrelated) and degree of engraftment are not the key for successful treatment of CDI by FMT. However, CDI patients with IBD have higher proportion of the original community after FMT and lack of improvement of their IBD symptoms and increased episodes of CDI on long-term follow-up.

Keywords: Clostridium difficile infection; Fecal microbiota transplantation; Inflammatory bowel disease; Microbiome.

Fig. 1

a Principal Coordinates Analysis of the unweighted UniFrac distances, showing a significant change in the phylogenetic diversity between patients with CDI, 7 and 28 days after fecal microbiota transplant (PERMANOVA p < 0.05). b Change in dysbiosis index following fecal microbiota transplant in patients with CDI with or without IBD, demonstrating that the microbial dysbiosis index values were significantly higher in patients with CDI compared to donors (Mann-Whittney’s U, p < 0.05). c Spearman correlation to donor stool 7 and 28 days following fecal microbiota transplantation demonstrating that the fecal microbial communities from patients with CDI were distinct from donor communities prior to transplant (Spearman’s r < 0.2 for all subjects)

Fig. 2

a, b Subjects with IBD retain a higher proportion of their original communities (*Mann-Whitney p < 0.05 at day 7 and p = 0.06 at day 28, and a significantly lower proportion of new communities (*Mann-Whitney p < 0.05 at days 7 and 28), as compared to the patients without IBD using SourceTracker. c Bacterial taxa that change significantly in patients with IBD after FMT (ANCOM p < 0.05, corrected for multiple comparisons using Bonferroni-Holm’s method). d Bacterial taxa that change significantly in patients without IBD after FMT (ANCOM p < 0.05, corrected for multiple comparisons using Bonferroni-Holm’s method). e Change in phylogenetic diversity-based alpha diversity 7 and 28 days following fecal microbiota transplant in patients with CDI with and without IBD (Mann-Whitney’s U p < 0.001)