Novel,non-colonizing,single-strain live biotherapeutic product ADS024 protects against Clostridioides difficile infection challenge in vivo  

作　　者：Christopher K Murphy Michelle M O’Donnell James W Hegarty Sarah Schulz Colin Hill R Paul Ross Mary C Rea Ronald Farquhar Laurent Chesnel 

机构地区：[1]Research and Development,Adiso Therapeutics Inc.,Concord,MA 01742,United States [2]APC Microbiome Ireland,University College Cork,Cork T12 K8AF,Ireland [3]Teagasc Food Research Centre,Moorepark Fermoy,Cork P61 C996,Ireland [4]Executive Leadership Team,Adiso Therapeutics Inc.,Concord,MA 01742,United States

出　　处：《World Journal of Gastrointestinal Pathophysiology》2023年第4期71-85,共15页世界胃肠病理生理学杂志（英文版）（电子版）

摘　　要：BACKGROUND The Centers for Disease Control and Prevention estimate that Clostridioides difficile(C.difficile)causes half a million infections(CDI)annually and is a major cause of total infectious disease death in the United States,causing inflammation of the colon and potentially deadly diarrhea.We recently reported the isolation of ADS024,a Bacillus velezensis(B.velezensis)strain,which demonstrated direct in vitro bactericidal activity against C.difficile,with minimal collateral impact on other members of the gut microbiota.In this study,we hypothesized that in vitro activities of ADS024 will translate in vivo to protect against CDI challenge in mouse models.AIM To investigate the in vivo efficacy of B.velezensis ADS024 in protecting against CDI challenge in mouse models.METHODS To mimic disruption of the gut microbiota,the mice were exposed to vancomycin prior to dosing with ADS024.For the mouse single-dose study,the recovery of ADS024 was assessed via microbiological analysis of intestinal and fecal samples at 4 h,8 h,and 24 h after a single oral dose of 5×108 colony-forming units(CFU)/mouse of freshly grown ADS024.The single-dose study in miniature swine included groups that had been pre-dosed with vancomycin and that had been exposed to a dose range of ADS024,and a group that was not pre-dosed with vancomycin and received a single dose of ADS024.The ADS024 colonies[assessed by quantitative polymerase chain reaction(qPCR)using ADS024-specific primers]were counted on agar plates.For the 28-d miniature swine study,qPCR was used to measure ADS024 levels from fecal samples after oral administration of ADS024 capsules containing 5×109 CFU for 28 consecutive days,followed by MiSeq compositional sequencing and bioinformatic analyses to measure the impact of ADS024 on microbiota.Two studies were performed to determine the efficacy of ADS024 in a mouse model of CDI:Study 1 to determine the effects of fresh ADS024 culture and ADS024 spore preparations on the clinical manifestations of CDI in mice,and Study 2 to compa

关 键 词：Gut Single-strain live biotherapeutic product ADS024 Clostridioides difficile Clostridioides difficile challenge model Microbiota 

分 类 号：R575[医药卫生—消化系统]