Background Microbiota-based treatments are effective in preventing recurrent Clostridioides difficile infection. Fecal microbiota, live-jslm (REBYOTA; RBL, previously RBX2660) was shown to prevent recurrent C difficile infection in a phase 3 clinical trial (PUNCH CD3) based on a randomized, double-blinded, placebo-controlled design. Methods Stool samples from participants in PUNCH CD3 who received a single blinded dose of rectally administered RBL or placebo were sequenced to determine microbial community composition and calculate the Microbiome Health Index for postantibiotic dysbiosis. The composition of bile acids (BAs) in the same samples was quantified by liquid chromatography–mass spectrometry. Relationships between BA composition and microbiota community structure and correlations with treatment outcomes were assessed. Results Before administration, Gammaproteobacteria and Bacilli dominated the microbiota community, and primary BAs were more prevalent than secondary BAs. Clinical success after administration correlated with shifts to predominantly Bacteroidia and Clostridia, a significant increase in Microbiome Health Index for postantibiotic dysbiosis, and a shift from primary to secondary BAs. Several microbiota and BA changes were more extensive in RBL-treated responders as compared with placebo-treated responders, and microbiota changes correlated with BA changes. Conclusions Clinical response and RBL administration were associated with significant restoration of microbiota and BA composition. Clinical Trials Registration NCT03244644 (https://clinicaltrials.gov/ct2/show/NCT03244644).

中文翻译：

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粪便微生物群给药后的微生物组和代谢组恢复，Live-jslm （REBYOTA） 预防复发性艰难梭菌感染


背景 基于微生物群的治疗可有效预防艰难梭菌感染复发。粪便微生物群，live-jslm （REBYOTA;RBL，以前RBX2660）在基于随机、双盲、安慰剂对照设计的 3 期临床试验 （PUNCH CD3） 中被证明可以预防复发性艰难梭菌感染。方法 对接受单剂直肠给药 RBL 或安慰剂的 PUNCH CD3 参与者的粪便样本进行测序，以确定微生物群落组成并计算抗生素后菌群失调的微生物组健康指数。通过液相色谱-质谱法定量相同样品中胆汁酸 （BAs） 的组成。评估 BA 组成与微生物群群结构之间的关系以及与治疗结果的相关性。结果 给药前，γ 变形菌门和芽孢杆菌在菌群群落中占主导地位，原发性 BAs 比次级 BAs 更普遍。给药后的临床成功与向主要拟杆菌属和梭状芽胞杆菌属的转变、抗生素后菌群失调的微生物组健康指数的显着增加以及从原发性 BAs 向继发性 BAs 的转变相关。与安慰剂治疗的反应者相比，RBL 治疗的反应者中的几种微生物群和 BA 变化更广泛，并且微生物群变化与 BA 变化相关。结论 临床反应和 RBL 给药与微生物群和 BA 组成的显着恢复相关。临床试验注册NCT03244644 （https://clinicaltrials.gov/ct2/show/NCT03244644）.