Haifer Craig, Paramsothy Sudarshan, Borody Thomas J, Clancy Annabel, Leong Rupert W, Kaakoush Nadeem O
Concord Clinical School, The University of Sydney, Sydney, Australia.
Gastroenterology Department, Concord Repatriation General Hospital, Sydney, Australia.
mSystems. 2021 Feb 2;6(1):e00905-20. doi: 10.1128/mSystems.00905-20.
Oral lyophilized fecal microbiota transplantation (FMT) is effective in recurrent infection (CDI); however, limited data exist on its efficacy in primary CDI and long-term microbial engraftment. Patients with primary or recurrent CDI were prospectively enrolled to receive oral FMT. Changes in the bacterial and fungal communities were characterized prior to and up to 6 months following treatment. A total of 37 patients with CDI (15 primary, 22 recurrent) were treated with 6 capsules each containing 0.35-g lyophilized stool extract. A total of 33 patients (89%) had sustained CDI cure, of whom 3 required a second course. There were no safety signals identified. FMT significantly increased bacterial diversity and shifted composition toward donor profiles in responders but not in nonresponders, with robust donor contribution observed to 6 months following FMT ( < 0.001). Responders showed consistent decreases in and increases in sp. to levels seen in donors. Mycobiome profiling revealed an association with FMT failure and increases in one taxon, as well as coexclusion relationships between sp. and bacterial taxa enriched in both donors and responders. Primary CDI was associated with more robust changes in the bacterial community than those with recurrent disease. Oral FMT leads to durable microbial engraftment in patients with primary and recurrent CDI, with several microbial taxa being associated with therapy outcome. Novel coexclusion relationships between bacterial and fungal species support the clinical relevance of transkingdom dynamics. infection (CDI) is a substantial health concern worldwide, complicated by patterns of increasing antibiotic resistance that may impact primary treatment. Orally administered fecal microbiota transplantation (FMT) is efficacious in the management of recurrent CDI, with specific bacterial species known to influence clinical outcomes. To date, little is known about the efficacy of FMT in primary CDI and the impact of the mycobiome on therapeutic outcomes. We performed matched bacterial and fungal sequencing on longitudinal samples from a cohort of patients treated with oral FMT for primary and recurrent CDI. We validated many bacterial signatures following oral therapy, confirmed engraftment of donor microbiome out to 6 months following therapy, and demonstrated coexclusion relationships between and two bacterial species in the gut microbiota, which has potential significance beyond CDI, including in the control of gut colonization by this fungal species.
口服冻干粪菌移植（FMT）对复发性艰难梭菌感染（CDI）有效；然而，关于其在原发性CDI中的疗效及长期微生物植入的数据有限。原发性或复发性CDI患者被前瞻性纳入以接受口服FMT。在治疗前及治疗后长达6个月对细菌和真菌群落的变化进行了特征分析。共有37例CDI患者（15例原发性，22例复发性）接受了6粒胶囊治疗，每粒胶囊含0.35 g冻干粪便提取物。共有33例患者（89%）实现了CDI的持续治愈，其中3例需要第二个疗程。未发现安全信号。FMT显著增加了有反应者的细菌多样性，并使菌群组成向供体特征转变，而无反应者则未出现这种情况，在FMT后6个月观察到有强大的供体贡献（<0.001）。有反应者的某菌属水平持续下降，另一菌属水平上升至供体所见水平。真菌群落分析揭示了与FMT失败以及一个真菌分类群增加的关联，以及该真菌与供体和有反应者中均富集的细菌分类群之间的共排斥关系。与复发性疾病相比，原发性CDI与细菌群落更显著的变化相关。口服FMT可使原发性和复发性CDI患者实现持久的微生物植入，有几个微生物分类群与治疗结果相关。细菌和真菌物种之间新的共排斥关系支持了跨界动态的临床相关性。艰难梭菌感染（CDI）是全球范围内一个重大的健康问题，因抗生素耐药性增加的模式而变得复杂，这可能影响初始治疗。口服粪菌移植（FMT）在复发性CDI的管理中有效，已知特定细菌物种会影响临床结果。迄今为止，关于FMT在原发性CDI中的疗效以及真菌群落对治疗结果的影响知之甚少。我们对一组接受口服FMT治疗原发性和复发性CDI患者的纵向样本进行了细菌和真菌测序匹配。我们验证了口服治疗后的许多细菌特征，证实治疗后6个月供体微生物群的植入，并证明了该真菌与肠道微生物群中两种细菌物种之间的共排斥关系，这在CDI之外具有潜在意义，包括在控制该真菌物种的肠道定植方面。
