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在体外人体肠道模型中评估发现,口服粪菌移植胶囊在抗生素破坏后重建微生物群方面与灌肠一样有效。

An Oral FMT Capsule as Efficient as an Enema for Microbiota Reconstruction Following Disruption by Antibiotics, as Assessed in an In Vitro Human Gut Model.

作者信息

Verdier Cécile, Denis Sylvain, Gasc Cyrielle, Boucinha Lilia, Uriot Ophélie, Delmas Dominique, Dore Joël, Le Camus Corentin, Schwintner Carole, Blanquet-Diot Stéphanie

机构信息

UMR 454 MEDIS, Université Clermont Auvergne, INRAe, F-63000 Clermont-Ferrand, France.

MaaT Pharma, F-69007 Lyon, France.

出版信息

Microorganisms. 2021 Feb 11;9(2):358. doi: 10.3390/microorganisms9020358.

Abstract

Fecal microbiota transplantation (FMT) is an innovative therapy already used in humans to treat infections associated with massive use of antibiotics. Clinical studies are obviously the gold standard to evaluate FMT efficiency but remain limited by regulatory, ethics, and cost constraints. In the present study, an in vitro model of the human colon reproducing medically relevant perturbation of the colonic ecosystem by antibiotherapy was used to compare the efficiency of traditional FMT enema formulations and a new oral capsule in restoring gut microbiota composition and activity. Loss of microbial diversity, shift in bacterial populations, and sharp decrease in fermentation activities induced in vivo by antibiotherapy were efficiently reproduced in the in vitro model, while capturing inter-individual variability of gut microbiome. Oral capsule was as efficient as enema to decrease the number of disturbed days and bacterial load had no effect on enema performance. This study shows the relevance of human colon models as an alternative approach to in vivo assays during preclinical studies for evaluating FMT efficiency. The potential of this in vitro approach could be extended to FMT testing in the management of many digestive or extra-intestinal pathologies where gut microbial dysbiosis has been evidenced such as inflammatory bowel diseases, obesity or cancers.

摘要

粪便微生物群移植(FMT)是一种已应用于人类治疗与大量使用抗生素相关感染的创新疗法。临床研究显然是评估FMT疗效的金标准,但仍受到监管、伦理和成本限制。在本研究中,使用一种体外人结肠模型,该模型通过抗生素疗法再现了与医学相关的结肠生态系统扰动,以比较传统FMT灌肠制剂和一种新型口服胶囊在恢复肠道微生物群组成和活性方面的疗效。抗生素疗法在体内诱导的微生物多样性丧失、细菌种群变化和发酵活性急剧下降在体外模型中得到有效再现,同时捕捉到了肠道微生物组的个体间变异性。口服胶囊在减少干扰天数方面与灌肠一样有效,而细菌负荷对灌肠效果没有影响。这项研究表明,在临床前研究中,人类结肠模型作为评估FMT疗效的体内试验的替代方法具有相关性。这种体外方法的潜力可以扩展到FMT测试,用于管理许多已证实存在肠道微生物失调的消化或肠道外疾病,如炎症性肠病、肥胖症或癌症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d161/7918368/2216aa42474a/microorganisms-09-00358-g001.jpg

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