Changes in Composition of the Gut Bacterial Microbiome after Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection in a Pediatric Heart Transplant Patient

Abstract

The microbiome is increasingly recognized as an important influence on human health and many of the comorbidities that affect patients after solid organ transplantation (SOT) have been shown to involve changes in gut bacterial populations. Thus, microbiome changes in an individual patient may have important health implications after SOT but this area remains understudied. We describe changes in the composition of the fecal microbiome from a pediatric heart transplant recipient before and >2.5 years after he underwent repeated fecal microbiota transplantation (FMT) for recurrent Clostridium difficile infection (CDI). With both documented episodes of CDI, there was marked loss of bacterial diversity with overgrowth of Proteobacteria (>98.9% of phyla identified) associated with symptomatic colitis that was corrected after FMT. We hypothesize that a second CDI occurring after FMT was related to incomplete restoration of normal bowel flora post-FMT with relative deficiencies of the phyla Firmicutes and Bacteroidetes and the families Lachnospiraceae and Ruminococcaceae. Following the second FMT, there was a gradual shift in gut bacterial composition coincident with the recipient developing lymphonodular hyperplasia of the colon and painless hematochezia that resolved with discontinuation of mycophenolate mofetil (MMF). This case documents dynamic changes in the bacterial microbiome after FMT and suggests that MMF may influence the gut microbiome with consequences for the patient.

Keywords: fecal microbiota transplant; heart transplantation; immunosuppression; microbiome; pediatric.

Figure 1

Proteobacteria predominates with Clostridium difficile infection (CDI). Bar plots showing the relative abundance of bacterial phyla in stool samples collected from the donor and recipient before and after fecal microbiota transplantation (FMT). The five donor samples are stable with a predominance of Firmicutes (yellow). When the patient has symptomatic CDI, there is an almost complete replacement of normal stool flora (dominated by Firmicutes) with Proteobacteria (pink).

Figure 2

Loss of alpha diversity with Clostridium difficile infection. Shannon (alpha) diversity reflects diversity within a sample. For the five sample groups examined (Donor, Post_FMT1, Post_FMT2, Pre_FMT1, and Pre_FMT2), there is a marked loss of bacterial diversity within the two samples prior to fecal microbiota transplantation (FMT) compared to the pooled Donor and Post-FMT samples that show comparable diversity.

Figure 3

Dynamic beta diversity in our pediatric transplant patient. Changes in beta diversity reflect changes in composition between samples. The non-metric multidimensional scaling (NMDS) plot shows changes in beta diversity for donor and recipient stool samples over time. The five donor samples (red circles) remain clustered together with stable diversity but there are large changes in the patient samples before (purple and yellow circles) and after fecal microbiota transplantation (FMT) (blue and green circles).

Figure 4

Deficiencies in bacterial families after the first fecal microbiota transplantation (FMT). Differential abundance (x-axis) of bacterial families (y-axis) in patient/recipient stool relative to the donor after the first (FMT1) and second FMT (FMT2). Within the phylum Firmicutes, there are relative deficiencies of the families Ruminococcaceae and Lachnospiraceae (indicated by increased number of green circles to the left of 0) and the phylum Bacteroidetes (blue circles) after FMT1.