Bacterial and viral assemblages in ulcerative colitis patients following fecal microbiota and fecal filtrate transfer.

Abstract

Fecal microbiota filtrate transfer is discussed as a safe alternative to fecal microbiota transfer (FMT) to treat ulcerative colitis. We investigated modulation of viral and bacterial composition during fecal microbiota filtrate transfer followed by FMT in six patients with active ulcerative colitis (where clinical activity improved in three patients after filtrate transfer) and combined 16S ribosomal RNA gene amplicon sequencing with a virome analysis pipeline including fast viral particle enrichment and metagenome mapping to detect frequencies of 45,033 reference bacteriophage genomes. We showed that after antibiotic treatment and during filtrate transfer, the bacterial community typically adopted a stable composition distinct to that before antibiotic treatment, with no change toward a donor community. FMT in contrast typically changed the bacterial community to a community with similarity to donor(s). There were no indications of an establishment of predominant donor viruses during filtrate transfer but a remodeling of the virome. In contrast, the establishment of donor viruses during FMT correlated with the predicted hosts established during such transfer. Our approach warrants further investigation in a randomized trial to evaluate larger therapeutic interventions in a comparable and efficient manner.