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

肠道微生物介导的小分子信号传导和对入侵微生物的抵抗力

• 批准号: 10218204
• 负责人: Ansel Hsiao
• 金额: $ 35.92万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-11 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10218204
• 关键词: Acute; Adult; Affect; Animal Model; Animals; Area; Bacteria; Bacterial Infections; Behavior; Biochemical; Biological Models; Biological Process; Cholera; Communicable Diseases; Communities; Country; Disease; Environment; Gastrointestinal tract structure; Gnotobiotic; Human; Human Microbiome; Individual Differences; Infection; Infection prevention; Invaded; Mediating; Modeling; Modification; Pathogenesis; Predisposition; Prevention; Research; Resistance; Risk Factors; Sanitation; Signaling Molecule; Structure; Study models; Therapeutic; Vibrio cholerae; Vibrio cholerae infection; combat; commensal microbes; cost; diarrheal disease; disorder risk; gut microbiome; gut microbiota; improved; microbial; microbiome; microorganism; mortality; mouse model; pathogen; pathogenic bacteria; prevent; prophylactic; small molecule; suckling

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.

细菌弧菌霍乱引起霍乱，霍乱是一种毁灭性的腹泻疾病，影响了数百万的人 每年全球。霍乱在许多遭受卫生不良的地区是地方性的，并施加了 在死亡和疾病方面，巨大的负担通常在那些最不能力负担的国家。尽管 了解V.霍乱如何引起疾病的进步，仍然缺乏防止该疾病的机制 霍乱传播。我们以前的研究发现，肠道微生物组或 所有人类胃肠道的居民细菌社区，介导对霍乱五的易感性 感染。我们假设共生微生物的个体差异可能是霍乱的危险因素。 该建议旨在确定肠道微生物组的结构与 V.霍乱殖民并引起疾病。病原体 - 微生物组相互作用的研究受到缺乏的限制 合适的动物模型，这是霍乱研究特别严重的问题，因为 许多动物模型和人类之间的病原体不同，而其他模型则受到成本的限制， 可用性。我们已经开始适应V.霍乱的流行且容易获得的动物模型 发病机理，哺乳小鼠的模型，以建立人类微生物组 感染。使用这些和gnotobiotic成人定植模型，我们将确定人类肠道如何 微生物组将肠道的生化环境驱动到抗病机构或易感状态。这些 机制可能决定成人肠道微生物群落的建立和组成，因此 确定个性化的传染病风险。这些研究将提高模型的可访问性 研究肠道微生物组如何影响肠道的细菌感染，并确定预防性的新靶 和肠道微生物组的治疗操作以对抗V.霍乱。

项目成果

Protocol for Microbiome Transplantation in Suckling Mice during Vibrio cholerae Infection to Study Commensal-Pathogen Interactions.

• DOI: 10.1016/j.xpro.2020.100200
• 发表时间: 2020-12-18
• 期刊: STAR protocols
• 作者: Alavi S;Hsiao A
• 通讯作者: Hsiao A

Microbiota-Associated Biofilm Regulation Leads to Vibrio cholerae Resistance Against Intestinal Environmental Stress.

• DOI: 10.3389/fcimb.2022.861677
• 发表时间: 2022
• 期刊: Frontiers in cellular and infection microbiology
• 影响因子: 5.7

The Interface of Vibrio cholerae and the Gut Microbiome.

• DOI: 10.1080/19490976.2021.1937015
• 发表时间: 2021-01
• 期刊: Gut microbes
• 影响因子: 12.2
• 作者: Cho JY;Liu R;Macbeth JC;Hsiao A
• 通讯作者: Hsiao A

Persistent exercise fatigue and associative learning deficits in combination with transient glucose dyshomeostasis in a mouse model of Gulf War Illness.

• DOI: 10.1016/j.lfs.2021.120094
• 发表时间: 2022-01-15
• 期刊: LIFE SCIENCES
• 影响因子: 6.1
• 作者: Kozlova, Elena, V;Carabelli, Bruno;Bishay, Anthony E.;Denys, Maximillian E.;Chinthirla, Devi B.;Tran, Jasmin D.;Hsiao, Ansel;Zur Nieden, Nicole, I;Curras-Collazo, Margarita C.
• 通讯作者: Curras-Collazo, Margarita C.

Induction of distinct neuroinflammatory markers and gut dysbiosis by differential pyridostigmine bromide dosing in a chronic mouse model of GWI showing persistent exercise fatigue and cognitive impairment.

• DOI: 10.1016/j.lfs.2021.120153
• 发表时间: 2022-01-01
• 期刊: Life sciences
• 影响因子: 6.1
• 作者: Kozlova EV;Carabelli B;Bishay AE;Liu R;Denys ME;Macbeth JC;Piamthai V;Crawford MS;McCole DF;Zur Nieden NI;Hsiao A;Curras-Collazo MC
• 通讯作者: Curras-Collazo MC