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DOP080 Low viral richness at baseline in ulcerative ulcerative colitis associated with faecal microbiota transplantation success

Conceição-Neto N.*1, Deboutte W.1, Dierckx T.1, Machiels K.2, Wang J.1,3, Yinda C.1, Maes P.1, Van Ranst M.1, Joossens M.1,3, Raes J.1,3, Vermeire S.2, Matthijnssens J.1

1KU Leuven, Rega Institute, Department of Microbiology and Immunology, Leuven, Belgium 2KU Leuven, TARGID, Department of Translational Research Centre for GastroIntestinal Disorders (TARGID), Leuven, Belgium 3VIB, Center for the Biology of Disease, Leuven, Belgium

Background

Faecal microbiota transplantation (FMT) has been seen as a promising tool in inflammatory bowel disease (IBD), but its use remains controversial. Bacteriome dysbiosis in IBD is well established, however the role of viruses is still understudied. Recently, an increased viral richness together with decreased bacterial diversity has been associated with IBD. We accessed the viral longitudinal dynamics in nine ulcerative colitis (UC) patients that underwent FMT (Figure). Of these, two patients (1 and 3, figure) presented endoscopic and long-term (>2-years) remission after FMT. However, the first FMT for patient 3 was followed by pneumonia and a course of antibiotics, and only sample related to the second FMT, of which no follow-up samples were available, were analysed.

Figure 1. Overview of the sample collection analysed for the virome dynamics.

Methods

Viral particles were purified from faeces using protocol NetoVIR and subsequently shotgun sequenced on an Illumina platform. Sequences were trimmed, de novo assembled, translated and compared to a protein database for taxonomic annotation. Richness and diversity were calculated using the vegan package in R.

Results

A higher viral richness at baseline was observed (p=0.023) in patients (n=9) when compared to their donors (n=8). When comparing all longitudinal samples from FMT responders (n=7) and non-responders (n=43), a lower richness (p=0.0005) was found for the responders. Comparing samples collected before FMT (baseline) from patients based on their outcome showed that responders (n=2) already presented a trend towards a lower richness (p=0.056) compared to non-responders (n=7). Finally, no significant differences could be observed (p=0.286) in viral richness of donors and outcome of patients.

Transferred phylotypes were defined as viral genera present in the donor sample and increased in the patient samples post-transplantation. We observed that in the responder with longitudinal data available, 8 viral genera were transferred, while the 6 non-responders, presented on average 32 transferred species. Since no samples post-transplantation were available for patient 3 we could not further verify this observation.

Conclusion

Our data confirms that diseased individuals present a higher viral richness and our study suggests that lower viral richness at baseline is associated with a good FMT outcome. Interestingly, the responder presented less transferred viral genera, in line with previous findings that a lower viral diversity is beneficial, suggesting that pre-screening of patients could lead to an increased success of FMT.