Ken F Blount, Romeo Papazyan, Nicky Ferdyan, Karthik Srinivasan, Carlos Gonzalez, William D Shannon, Bryan C Fuchs
{"title":"服用粪便微生物群活体-jslm (REBYOTA®) 预防艰难梭菌复发性感染后的微生物组和代谢组恢复。","authors":"Ken F Blount, Romeo Papazyan, Nicky Ferdyan, Karthik Srinivasan, Carlos Gonzalez, William D Shannon, Bryan C Fuchs","doi":"10.1093/infdis/jiae418","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>Clinical response and RBL administration were associated with significant restoration of microbiota and BA composition.</p><p><strong>Clinical trials registration: </strong>NCT03244644 (https://clinicaltrials.gov/ct2/show/NCT03244644).</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e1022-e1033"},"PeriodicalIF":4.5000,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247815/pdf/","citationCount":"0","resultStr":"{\"title\":\"Microbiome and Metabolome Restoration After Administration of Fecal Microbiota, Live-jslm (REBYOTA) for Preventing Recurrent Clostridioides difficile Infection.\",\"authors\":\"Ken F Blount, Romeo Papazyan, Nicky Ferdyan, Karthik Srinivasan, Carlos Gonzalez, William D Shannon, Bryan C Fuchs\",\"doi\":\"10.1093/infdis/jiae418\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>Clinical response and RBL administration were associated with significant restoration of microbiota and BA composition.</p><p><strong>Clinical trials registration: </strong>NCT03244644 (https://clinicaltrials.gov/ct2/show/NCT03244644).</p>\",\"PeriodicalId\":50179,\"journal\":{\"name\":\"Journal of Infectious Diseases\",\"volume\":\" \",\"pages\":\"e1022-e1033\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2025-07-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247815/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Infectious Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/infdis/jiae418\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Infectious Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/infdis/jiae418","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景:基于微生物群的治疗可有效预防艰难梭菌复发性感染(rCDI)。在一项第 3 期随机双盲安慰剂对照临床试验(PUNCH™ CD3)中,粪便微生物活菌群(REBYOTA®;RBL,原名 RBX2660)被证明可预防 rCDI:对参加 PUNCH™ CD3 试验、接受单次盲剂量直肠给药 RBL 或安慰剂的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微生物组健康指数 (MHI-A)。同一样本中胆汁酸(BA)的组成采用液相色谱质谱法进行量化。评估了胆汁酸组成与微生物群落结构之间的关系以及与治疗结果的相关性:结果:用药前,微生物群落中主要是伽马蛋白菌和芽孢杆菌,原生生物碱比次生生物碱更为普遍。用药后的临床成功与转向以类杆菌和梭状芽胞杆菌为主、MHI-A显著增加以及从初级生物群转向次级生物群有关。与安慰剂治疗应答者相比,RBL 治疗应答者的微生物群和 BA 变化更为广泛,微生物群变化与 BA 变化相关:临床试验注册:临床试验注册:NCT03244644。
Microbiome and Metabolome Restoration After Administration of Fecal Microbiota, Live-jslm (REBYOTA) for Preventing Recurrent Clostridioides difficile Infection.
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.
期刊介绍:
Published continuously since 1904, The Journal of Infectious Diseases (JID) is the premier global journal for original research on infectious diseases. The editors welcome Major Articles and Brief Reports describing research results on microbiology, immunology, epidemiology, and related disciplines, on the pathogenesis, diagnosis, and treatment of infectious diseases; on the microbes that cause them; and on disorders of host immune responses. JID is an official publication of the Infectious Diseases Society of America.