Administration of defined microbiota is protective in a murine Salmonella infection model.
Administration of defined microbiota is protective in a murine Salmonella infection model.
复制标题
DOI：
10.1038/srep16094
复制
发表时间：
2015-11-04
影响因子：
4.6
通讯作者：
Petrof EO
中科院分区：
文献类型：
--
作者：
Martz SL;McDonald JA;Sun J;Zhang YG;Gloor GB;Noordhof C;He SM;Gerbaba TK;Blennerhassett M;Hurlbut DJ;Allen-Vercoe E;Claud EC;Petrof EO
鼠伤寒沙门氏菌（Salmonella typhimurium）是腹泻的主要原因，在世界范围内引起显著的发病率和死亡率，并且已知肠道微生物群的扰动会增加对肠道感染的易感性。本研究的目的是调查由33种细菌菌株组成的微生物生态系统治疗剂（MET-1）是否也可以预防艰难梭菌感染，该菌株从人粪便中分离出来，以前曾用于治疗复发性艰难梭菌感染的患者。鼠伤寒病C57 BL/6小鼠在接受MET-1或对照之前用链霉素预处理，然后用S.鼠伤寒。体重减轻、血清细胞因子水平和S.测定鼠伤寒沙门氏菌脾移位。通过免疫荧光观察NF-κB核染色、中性粒细胞聚集和紧密连接蛋白（claudin-1、ZO-1）的定位。接受MET-1的感染小鼠体重减轻较少，血清细胞因子减少，NF-κB核染色减少，盲肠中中性粒细胞浸润减少。MET-1还保留了盲肠紧密连接蛋白的表达，并减少了S.鼠伤寒沙门氏菌移位至脾脏。值得注意的是，MET-1没有减少肠道中沙门氏菌的CFU。MET-1可以通过保留紧密连接来减弱全身感染，从而抑制S.鼠伤寒杆菌进入体循环因此，MET-1可能对肠道感染具有保护作用。艰难感染
Salmonella typhimurium is a major cause of diarrhea and causes significant morbidity and mortality worldwide, and perturbations of the gut microbiota are known to increase susceptibility to enteric infections. The purpose of this study was to investigate whether a Microbial Ecosystem Therapeutic (MET-1) consisting of 33 bacterial strains, isolated from human stool and previously used to cure patients with recurrent Clostridium difficile infection, could also protect against S. typhimurium disease. C57BL/6 mice were pretreated with streptomycin prior to receiving MET-1 or control, then gavaged with S. typhimurium. Weight loss, serum cytokine levels, and S. typhimurium splenic translocation were measured. NF-κB nuclear staining, neutrophil accumulation, and localization of tight junction proteins (claudin-1, ZO-1) were visualized by immunofluorescence. Infected mice receiving MET-1 lost less weight, had reduced serum cytokines, reduced NF-κB nuclear staining, and decreased neutrophil infiltration in the cecum. MET-1 also preserved cecum tight junction protein expression, and reduced S. typhimurium translocation to the spleen. Notably, MET-1 did not decrease CFUs of Salmonella in the intestine. MET-1 may attenuate systemic infection by preserving tight junctions, thereby inhibiting S. typhimurium from gaining access to the systemic circulation. We conclude that MET-1 may be protective against enteric infections besides C. difficile infection.