Oliphant Kaitlyn, Cochrane Kyla, Schroeter Kathleen, Daigneault Michelle C, Yen Sandi, Verdu Elena F, Allen-Vercoe Emma
Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada
Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada.
mSystems. 2020 Jan 28;5(1):e00404-19. doi: 10.1128/mSystems.00404-19.
Fecal microbiota transplantation (FMT) is a proposedly useful strategy for the treatment of gastrointestinal (GI) disorders through remediation of the patient gut microbiota. However, its therapeutic success has been variable, necessitating research to uncover mechanisms that improve patient response. Antibiotic pretreatment has been proposed as one method to enhance the success rate by increasing niche availability for introduced species. Several limitations hinder exploring this hypothesis in clinical studies, such as deleterious side effects and the development of antimicrobial resistance in patients. Thus, the purpose of this study was to evaluate the use of an , bioreactor-based, colonic ecosystem model as a form of preclinical testing by determining how pretreatment with the antibiotic rifaximin influenced engraftment of bacterial strains sourced from a healthy donor into an ulcerative colitis-derived defined microbial community. Distinct species integrated under the pretreated and untreated conditions, with the relative rifaximin resistance of the microbial strains being an important influencer. However, both conditions resulted in the integration of taxa from clusters IV and XIVa, a concomitant reduction of , and similar decreases in metabolites associated with poor health status. Our results agree with the findings of similar research in the clinic by others, which observed no difference in primary patient outcomes whether or not patients were given rifaximin prior to FMT. We therefore conclude that our model is useful for screening for antibiotics that could improve efficacy of FMT when used as a pretreatment. Patients with gastrointestinal disorders often exhibit derangements in their gut microbiota, which can exacerbate their symptoms. Replenishing these ecosystems with beneficial bacteria through fecal microbiota transplantation is thus a proposedly useful therapeutic; however, clinical success has varied, necessitating research into strategies to improve outcomes. Antibiotic pretreatment has been suggested as one such approach, but concerns over harmful side effects have hindered testing this hypothesis clinically. Here, we evaluate the use of bioreactors supporting defined microbial communities derived from human fecal samples as models of the colonic microbiota in determining the effectiveness of antibiotic pretreatment. We found that relative antimicrobial resistance was a key determinant of successful microbial engraftment with rifaximin (broad-spectrum antibiotic) pretreatment, despite careful timing of the application of the therapeutic agents, resulting in distinct species profiles from those of the control but with similar overall outcomes. Our model had results comparable to the clinical findings and thus can be used to screen for useful antibiotics.
粪便微生物群移植（FMT）是一种通过修复患者肠道微生物群来治疗胃肠道（GI）疾病的潜在有效策略。然而，其治疗成功率各不相同，因此有必要开展研究以揭示能改善患者反应的机制。抗生素预处理被认为是一种通过增加引入菌种的生态位可利用性来提高成功率的方法。但临床研究在探索这一假设时存在一些限制，比如有害的副作用以及患者体内抗菌药物耐药性的产生。因此，本研究的目的是通过确定用抗生素利福昔明进行预处理如何影响源自健康供体的细菌菌株在溃疡性结肠炎衍生的特定微生物群落中的植入情况，来评估基于生物反应器的结肠生态系统模型作为一种临床前测试形式的用途。在预处理和未预处理条件下整合的不同菌种中，微生物菌株对利福昔明的相对耐药性是一个重要影响因素。然而，两种条件都导致了IV群和XIVa群分类单元的整合、某一菌种的同时减少以及与健康状况不佳相关的代谢物的类似减少。我们的结果与其他人在临床上的类似研究结果一致，即无论患者在FMT前是否接受利福昔明治疗，主要患者结局并无差异。因此，我们得出结论，当用作预处理时，我们的模型可用于筛选能提高FMT疗效的抗生素。患有胃肠道疾病的患者其肠道微生物群往往会出现紊乱，这会加重他们的症状。因此，通过粪便微生物群移植用有益细菌补充这些生态系统是一种潜在有效的治疗方法；然而，临床成功率各不相同，因此有必要研究改善治疗效果的策略。抗生素预处理被认为是这样一种方法，但对有害副作用的担忧阻碍了在临床上对这一假设进行检验。在这里，我们评估使用支持源自人类粪便样本的特定微生物群落的生物反应器作为结肠微生物群模型来确定抗生素预处理有效性的情况。我们发现，尽管仔细安排了治疗药物的应用时间，但相对抗菌耐药性是利福昔明（广谱抗生素）预处理成功实现微生物植入的关键决定因素，这导致与对照组不同的菌种分布，但总体结果相似。我们的模型结果与临床研究结果相当，因此可用于筛选有用的抗生素。
