Bethlehem Lukas, Estevinho Maria Manuela, Grinspan Ari, Magro Fernando, Faith Jeremiah J, Colombel Jean-Frederic
Department of Genomics and Genetic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Gastroenterology, Vila Nova de Gaia Espinho Hospital Center, Vila Nova de Gaia, Portugal; Unit of Pharmacology and Therapeutics, Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal.
Lancet Gastroenterol Hepatol. 2024 May;9(5):476-486. doi: 10.1016/S2468-1253(23)00441-7.
Microbiota therapeutics that transplant faecal material from healthy donors to people with mild-to-moderate ulcerative colitis have shown the potential to induce remission in about 30% of participants in small, phase 2 clinical trials. Despite this substantial achievement, the field needs to leverage the insights gained from these trials and progress towards phase 3 clinical trials and drug approval, while identifying the distinct clinical niche for this new therapeutic modality within inflammatory bowel disease (IBD) therapeutics. We describe the lessons that can be learned from past studies of microbiota therapeutics, from full spectrum donor stool to defined products manufactured in vitro. We explore the actionable insights these lessons provide on the design of near-term studies and future trajectories for the integration of microbiota therapeutics in the treatment of IBD. If successful, microbiota therapeutics will provide a powerful orthogonal approach (complementing or in combination with existing immunomodulatory drugs) to raise the therapeutic ceiling for the many non-responders and partial responders within the IBD patient population.
将健康供体的粪便物质移植给轻至中度溃疡性结肠炎患者的微生物群疗法，在小型2期临床试验中已显示出约30%的参与者有诱导缓解的潜力。尽管取得了这一重大成果，但该领域仍需利用从这些试验中获得的见解，推进到3期临床试验和药物审批阶段，同时在炎症性肠病（IBD）治疗中确定这种新治疗方式的独特临床定位。我们描述了从微生物群疗法的既往研究中可以吸取的经验教训，从全谱供体粪便到体外制造的特定产品。我们探讨了这些经验教训为近期研究设计以及微生物群疗法融入IBD治疗的未来发展轨迹提供的可操作见解。如果成功，微生物群疗法将提供一种强大的正交方法（补充或与现有免疫调节药物联合使用），以提高IBD患者群体中许多无反应者和部分反应者的治疗上限。
