Stable core virome despite variable microbiome after fecal transfer

Abstract

We recently described the 4.5-year time course of the enteric bacterial microbiota and virome of a patient cured from recurrent Clostridium difficile infection (rCDI) by fecal microbiota transplantation (FMT). Here, we extended the virome analyses and found the patient's phage population to exhibit highly donor-similar characteristics following FMT, which remained stable for the whole period tested (up to 7 months). Moreover, the detected viral populations of donor and patient exhibited comparable diversity and richness. These findings were unexpected since enteric viromes are normally highly variable, assumed to influence the bacterial host community and change with environmental conditions. In contrast to the virome, the bacterial microbiota varied indeed for more than 7 months with ongoing dysbiosis before it reached donor similarity. Our findings that are based on sequence information and protein domain analysis seem to suggest that stable phage properties correlate with successful FMT better than the changing bacterial communities. We speculate that we here preferentially detected a stable core virome, which dominated over a variable flexible virome that may have been too heterogeneous for experimental detection or was underrepresented in the databases. It will be interesting to analyze whether the enteric virome allows predictions for the clinical outcome of FMT for rCDI and other diseases such as inflammatory bowel disease or obesity.

Keywords: Clostridium difficile; core virome; fecal microbiota transplantation; long-term analysis; microbiome; sequencing; virome.

Figure 1.

(a) Timeline of fecal samples of donor (D0 and D4) and patient (P1 through P4) subjected to 16S rRNA gene sequencing (all samples) or metagenomic sequencing (samples D0 and P1-P3). (b) Relative abundances of bacterial phyla as inferred by 16S rRNA gene sequencing. (c) and (d) Relative proportions of bacterial phylum-specific (c) or phage-specific (d) Pfam domains identified from metagenomic ORFs. (e) Relative abundances of phage families identified by aligning phage-specific ORFs against tailed phage protein sequences of the NRPROT database. (f) Virus family-specific relative proportions of phage-specific Pfam domains identified from metagenomic ORFs.

Figure 2.

α diversity (Shannon's H’) and richness (Menhinick's D) measurements based on phage species taxonomically assigned by NRPROT (a) and on Pfam domain annotation (b). Sample identifiers D0 and P1-P3 are explained in Fig. 1a.