Bacteriophage transfer during faecal microbiota transplantation inClostridium difficileinfection is associated with treatment outcome

Abstract

ObjectiveFaecal microbiota transplantation (FMT) is effective for the treatment of recurrent Clostridium difficile infection (CDI). Studies have shown bacterial colonisation after FMT, but data on viral alterations in CDI are scarce. We investigated enteric virome alterations in CDI and the association between viral transfer and clinical outcome in patients with CDI.DesignUltra-deep metagenomic sequencing of virus-like particle preparations and bacterial 16S rRNA sequencing were performed on stool samples from 24 subjects with CDI and 20 healthy controls. We longitudinally assessed the virome and bacterial microbiome changes in nine CDI subjects treated with FMT and five treated with vancomycin. Enteric virome alterations were assessed in association with treatment response.ResultsSubjects with CDI demonstrated a significantly higher abundance of bacteriophage Caudovirales and a lower Caudovirales diversity, richness and evenness compared with healthy household controls. Significant correlations were observed between bacterial families Proteobacteria, Actinobacteria and Caudovirales taxa in CDI. FMT treatment resulted in a significant decrease in the abundance of Caudovirales in CDI. Cure after FMT was observed when donor-derived Caudovirales contigs occupied a larger fraction of the enteric virome in the recipients (p=0.024). In treatment responders, FMT was associated with alterations in the virome and the bacterial microbiome, while vancomycin treatment led to alterations in the bacterial community alone.ConclusionsIn a preliminary study, CDI is characterised by enteric virome dysbiosis. Treatment response in FMT was associated with a high colonisation level of donor-derived Caudovirales taxa in the recipient. Caudovirales bacteriophages may play a role in the efficacy of FMT in CDI.Trial registration numberNCT02570477

Review article: bacteriophages in gastroenterology—from biology to clinical applications

“…88 In a preliminary study, colonisation by donor-derived Caudovirales taxa following FMT was associated with better patient outcomes. 89 In another trial, the transfer of sterile filtrates from donor stool was sufficient to decrease symptoms in five patients with symptomatic C difficile colitis, possibly due to viral particles transmission. 90 In pre-clinical studies, phage cocktails efficiently reduced C difficile growth and proliferation.…”

Systematic review with meta‐analysis: review of donor features, procedures and outcomes in 168 clinical studies of faecal microbiota transplantation

“…52 Recent studies show that besides clinical factors, stool microbiome changes, for example bacteriophages, may be transferable and affect treatment outcome. 16 Recruitment of donors for FMT is challenging with only a small percentage ultimately accepted as donors. 31 Pooling stool from universal donors with standard screening protocols, for example in stool banks, may improve efficiency and cost-effectiveness, and multi-donor transplants may be associated with higher microbial diversity.…”

“…10 Several meta-analyses have reported data on the efficacy and safety of FMT for CDI but few have analysed donor characteristics or microbial profile. 2,[11][12][13][14][15][16] Even widely used protocols have highly variable donor selection methods which are mostly limited to screening for infections and co-morbidities. [17][18][19] We performed a systematic review of all FMT clinical studies without language restriction up to 29 August 2018.…”

Nucleic Acid Induced Interferon and Inflammasome Responses in Regulating Host Defense to Gastrointestinal Viruses

“…Therefore, although cause and consequence are always difficult to discriminate, it is tempting to speculate that there could indeed be link between altered viral dsRNA induced MDA-5 responses, enteric viral presence and T1D development. Adding to this suspicion, the success of fecal transfers in IBD patients has recently been associated with the gut virome composition (Conceição-Neto et al, 2017;Zuo et al, 2018). While at the moment they are mere correlations, there is no doubt that these observations will spark many future efforts investigating the response of the intestinal immune system to "commensal" and infectious viral nucleic acids.…”