Becattini Simone, Littmann Eric R, Carter Rebecca A, Kim Sohn G, Morjaria Sejal M, Ling Lilan, Gyaltshen Yangtsho, Fontana Emily, Taur Ying, Leiner Ingrid M, Pamer Eric G
Immunology Program, Sloan Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY
Lucille Castori Center for Microbes Inflammation and Cancer, Molecular Microbiology Core Facility, Memorial Sloan-Kettering Cancer Center, New York, NY.
J Exp Med. 2017 Jul 3;214(7):1973-1989. doi: 10.1084/jem.20170495. Epub 2017 Jun 6.
is a foodborne pathogen that causes septicemia, meningitis and chorioamnionitis and is associated with high mortality. Immunocompetent humans and animals, however, can tolerate high doses of without developing systemic disease. The intestinal microbiota provides colonization resistance against many orally acquired pathogens, and antibiotic-mediated depletion of the microbiota reduces host resistance to infection. Here we show that a diverse microbiota markedly reduces colonization of the gut lumen and prevents systemic dissemination. Antibiotic administration to mice before low dose oral inoculation increases growth in the intestine. In immunodeficient or chemotherapy-treated mice, the intestinal microbiota provides nonredundant defense against lethal, disseminated infection. We have assembled a consortium of commensal bacteria belonging to the Clostridiales order, which exerts in vitro antilisterial activity and confers in vivo resistance upon transfer into germ free mice. Thus, we demonstrate a defensive role of the gut microbiota against infection and identify intestinal commensal species that, by enhancing resistance against this pathogen, represent potential probiotics.
是一种食源性病原体，可导致败血症、脑膜炎和绒毛膜羊膜炎，并与高死亡率相关。然而，具有免疫能力的人类和动物能够耐受高剂量的 而不发生全身性疾病。肠道微生物群对许多经口获得的病原体提供定植抗性，抗生素介导的微生物群耗竭会降低宿主对感染的抵抗力。在这里，我们表明多样化的微生物群显著减少肠道腔内的 定植并防止全身扩散。在低剂量口服接种前给小鼠施用抗生素会增加肠道内的 生长。在免疫缺陷或化疗治疗的小鼠中，肠道微生物群对致死性播散感染提供非冗余防御。我们组建了一个属于梭菌目的共生细菌联合体，该联合体在体外具有抗李斯特菌活性，并在转移到无菌小鼠体内时赋予体内抗性。因此，我们证明了肠道微生物群对 感染的防御作用，并确定了通过增强对这种病原体的抗性而代表潜在益生菌的肠道共生物种。
