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 …

中文翻译：

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粪便吞噬菌体移植可缓解 IBD 患者的间歇性肠道炎症，移植时机很重要：小鼠临床前概念验证研究


我们饶有兴趣地阅读了 Lopetuso 等人关于 IBD（一种具有间歇性发作和肠道炎症缓解的难治性疾病）粪便微生物群移植 （FMT） 的罗马共识论文.1 根据临床试验的数据，它强调了 FMT 在治疗 IBD 和细菌移植引起的不良事件风险方面的适度疗效.1 因此，有必要进一步改进 FMT 以治疗 IBD .3 我们之前的研究发现 FMT 可以同时重新配置艰难梭菌感染患者的肠道细菌组和噬菌组;然而，噬菌体的重构更多地与长期肠道炎症的改善有关，这表明肠道噬菌体在对抗肠道病变中起着突出的作用.4-6 我们最近的研究在 IBD 患者的肠粘膜中发现了严重扰动的肠道噬菌体.7 8 令人惊讶的是，与急性发作的患者相比，缓解期患者的噬菌组-细菌组生态的扭曲更加明显， 暗示缓解期受扰动的粘膜噬菌可能“静止地”助长了疾病的发作.7 这些发现共同使我们假设，在缓解期而不是发作期，通过粪便噬菌体移植 （FPT） 靶向受扰动的肠道噬菌可能是治疗 IBD 的可行策略。受这一假设的启发，我们在具有间歇性、递增葡聚糖硫酸钠 （DSS） 挑战的 IBD 小鼠模型中进行了一项临床前概念验证研究（以模拟 IBD 的复发和缓解病程），据此，我们在第一轮 DSS 攻击（缓解期间施用 FPT （FPT-r） 与发作 （FPT-f））的不同干预时间移植了健康的粪便噬菌体，然后评估治疗......