Gut microbiome-mediated small-molecule signaling and resistance to invading microorganisms

霍乱弧菌导致霍乱，霍乱是一种毁灭性的腹泻疾病，影响着数百万人 每年在全球范围内。霍乱在许多卫生条件恶劣的地区流行，并造成 死亡率和疾病方面的巨大负担，往往是那些最负担不起的国家的负担。尽管 尽管对霍乱弧菌致病机理的了解取得了进展，但仍缺乏预防霍乱弧菌感染的机制 霍乱的蔓延。我们之前的研究发现，肠道微生物组的特定配置，或称 所有人胃肠道中的驻留细菌群落，介导了对霍乱弧菌的敏感性 感染。我们假设共生微生物的个体差异可能是霍乱的一个风险因素。 这项建议旨在确定肠道微生物组的结构和能力之间的关系 霍乱弧菌定植并致病。病原菌-微生物组相互作用的研究因缺乏而受到限制 合适的动物模型，这对霍乱研究来说是一个特别尖锐的问题，因为 病原体在许多动物模型和人类模型中是不同的，而其他模型受成本和 可用性。我们已经开始采用一种流行的、容易获得的霍乱弧菌动物模型。 发病机制，乳鼠模型，以允许在 感染。利用这些和诺维菌学的成体定植模型，我们将确定人类的肠道 微生物群使肠道的生化环境进入抗病原菌或敏感状态。这些 机制可能决定成人肠道微生物群落的建立和组成，从而 确定个性化传染病风险。这些研究将改善模型的可及性 研究肠道微生物群如何影响肠道细菌感染，并确定预防的新靶点 和肠道微生物群的治疗操作来对抗霍乱弧菌。

The bacterium Vibrio cholerae causes cholera, a devastating diarrhea disease that affects millions of people worldwide each year. Cholera is endemic in many areas that suffer from poor sanitation, and imposes an immense burden in terms of mortality and illness, often on those countries least able to afford it. Despite advances in understanding how V. cholerae causes disease, there is still a lack of mechanisms to prevent the spread of cholera. Our previous studies have found that specific configurations of the gut microbiome, or the community of resident bacteria in the gastrointestinal tract of all humans, mediate susceptibility to V. cholerae infection. We hypothesize that individual differences in commensal microbes may be a risk factor for cholera. This proposal aims to determine the relationship between the structure of the gut microbiome and the ability of V. cholerae to colonize and cause disease. Studies of pathogen-microbiome interactions are limited by a lack of suitable animal models, a problem that is particularly acute for cholera research, as the behavior of the pathogen differs between many animal models and humans, while other models are limited by cost and availability. We have begun to adapt a popular and readily accessible animal model of V. cholerae pathogenesis, the suckling mouse model, to allow for the establishment of human microbiomes prior to infection. Using these and gnotobiotic adult colonization models, we will determine how human gut microbiomes drive the biochemical milieu of the gut into pathogen-resistant or susceptible states. These mechanisms may determine the establishment and composition of the adult gut microbial community, and thus determine personalized infectious disease risk. These studies will improve the accessibility of models for studying how gut microbiomes influence bacterial infections of the gut, and identify new targets for prophylactic and therapeutic manipulations of the gut microbiome to combat V. cholerae.