Faecal phageome transplantation alleviates intermittent intestinal inflammation in IBD and the timing of transplantation matters: a preclinical proof-of-concept study in mice

Abstract

We read with interest the Rome Consensus paper on faecal microbiota transplantation (FMT) in IBD (a refractory disease with intermittent flare-ups and remissions of intestinal inflammation) by Lopetuso et al .1 It highlights modest efficacies of FMT in treating IBD and adverse event risks caused by bacteria transplantation, according to data from clinical trials.1 Hence, further refinement of FMT is warranted for IBD treatment.2 3 Our prior study found that FMT can simultaneously reconfigure the gut bacteriome and phageome in patients with Clostridioides difficile infection; however, the reconfiguration of phageome was associated more with a long-term intestinal inflammation amelioration, suggesting a prominent role for gut bacteriophages in combating intestinal pathologies.4–6 Our more recent studies discovered a critically perturbed gut phageome in the intestinal mucosa of patients with IBD.7 8 Surprisingly, the distortion in the phageome-bacteriome ecology was even more pronounced in patients in remission compared with those in flare-up, implying the perturbed mucosal phageome during remission might be ‘quiescently’ fuelling disease flare-up.7 These findings together led us to hypothesise that targeting the perturbed gut phageome by faecal phageome transplantation (FPT), during the remission phase rather than the flare-up phase, might be a viable strategy for treating IBD. Inspired by this hypothesis, we conducted a preclinical proof-of-concept study in an IBD mouse model with intermittent, step-up dextran sulfate sodium (DSS) challenges (to mimic the relapsing and remitting disease courses of IBD), whereby we transplanted healthy faecal phageome at different intervention timings on the first round of DSS challenge (FPT administered during remission (FPT-r) vs flare-up (FPT-f)) and then evaluated treatment …