Fecal microbiota transplant in ulcerative colitis patients: what is the role of the human gut virome and can it be used as a biomarker for predicting treatment success

The gut microbiota is a complex and diverse ecosystem consistent of viruses, bacteria, archaea, fungi and protozoa. It plays various important roles, such as protecting against invading pathogens and producing essential vitamins. However, sometimes this ecosystem gets disrupted, leading to a state known as gut dysbiosis. Gut dysbiosis has been linked to several diseases including ulcerative colitis (UC). To treat UC, patients are prescribed a range of therapies, such as biologicals, steroids, thiopurines or 5-aminosalicylates. Unfortunately, these treatments are only effective for a limited number of UC patients. In recent times, a potential new treatment option called fecal microbiota transplants (FMTs) has emerged. FMT treatment involves transferring fecal matter (or in other words transplanting the gut microbiota) from a healthy and well-screened donor into the gut of the recipient patient. However, FMT is not yet a standardized procedure, and various factors come into play, such as the selection of donor, the number of FMTs administered and the route of administration. To address this issue and optimize FMT treatment, a randomized controlled clinical trial called RESTORE-UC was initiated in Belgium. In this study, we investigated the role of the gut virome (the viral component of the gut microbiota) in UC patients undergoing FMT treatment. Our study involved a subset of 44 UC patients comprising a total of 315 fecal samples (baseline, week 4, week 8, week 12, month 6 and month 12) for further analysis. Our study aimed to achieve two main objectives: Firstly, we aimed to assess whether the fecal virome from the donor is effectively transplanted to the patient and observe how this transplantation process evolves over time. This would provide us with valuable insights into the dynamics of the virome during FMT treatment. Secondly, we sought to investigate whether the gut virome could be used as a biomarker for predicting the success of FMT treatment. By examining the virome composition and changes in relation to treatment outcomes, we aimed to determine if specific virome characteristics could serve as indicators of treatment effectiveness. By conducting this research, our intention was to contribute to the overarching objectives of the RESTORE-UC trial and gain a deeper understanding of the potential benefits and underlying mechanisms of FMT treatment in patients with UC.