Microbial Influence on Mucosal Homeostasis

微生物对粘膜稳态的影响

• 批准号: 10290877
• 负责人: Andrew S Neish
• 金额: $ 39万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10290877
• 关键词: Animals; Bacteria; Bifidobacterium; Biochemical; Biological Assay; Biology; Cell Proliferation; Colitis; Communicable Diseases; Communities; Complex; Data; Development; Differentiation and Growth; Disease model; Enterobacteriaceae; Enzymes; Epithelial; Escherichia coli; Event; Gene Expression; Generations; Genetic Transcription; Germ-Free; Gnotobiotic; Gut Mucosa; Health; Homeostasis; Immune; Immune System Diseases; Individual; Inflammatory; Injury; Intestines; Lactobacillus; Link; Long-Term Effects; Maintenance; Mediating; Metabolic Diseases; Microbe; Modeling; Mucous Membrane; Mus; NADPH Oxidase; Neonatal; Newborn Animals; Normal Range; Organism; Oxidation-Reduction; Participant; Pathologic; Pathologic Processes; Pathway interactions; Perception; Permeability; Phagocytes; Physiological; Physiology; Probiotics; Process; Production; Property; Reaction; Reactive Oxygen Species; Reporting; Role; Second Messenger Systems; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Signaling Protein; Structure; Surface; System; Taxonomy; Technology; Tissues; Work; Wound models; cell growth; cell growth regulation; commensal bacteria; commensal microbes; dysbiosis; gastrointestinal; gastrointestinal epithelium; gene product; gut bacteria; gut homeostasis; gut microbiota; human disease; in vivo; intestinal epithelium; intestinal homeostasis; member; microbial; microbial community; microbial host; microbiota; migration; mucosal microbiota; mutant; neonatal mice; normal microbiota; novel; pathogenic bacteria; response; targeted treatment

SUMMARY/ABSTRACT The gastrointestinal mucosa functions as an interface between the luminal contents and the underlying tissue compartments, and is thus vital in maintaining mucosal and systemic homeostasis. The gut lumen houses a numerically vast and taxonomically diverse prokaryotic microbiota. In health, the mucosa and microbiota thrive in a mutually beneficial symbiotic arrangement. Both host and microbe have evolved a complex system of mutual perception, response and reaction. These events are mediated in part by the ability of the intestinal epithelia to respond to specific members of the microbiota by the production of reactive oxygen species (ROS), that serve to activate multiple cellular pathways involved in the maintenance of gut homeostasis. This proposal will employ in vivo systems including extensive use of germ-free mice, or mice gnotobiotically colonized with known ROS inducing bacteria. Additionally, taxonomic analysis of microbiota in neonatal mice will be used to identify other bacteria with functional effects on the gut mucosa. The proposal will study microbial influences on known and novel signaling pathway, and characterize the regulatory effects on gut survival, differentiation and proliferation. Our overall objectives are to define the participants, events, and processes involved in host microbial contact and how this interaction influences intestinal homeostasis, development and restitution. ROS and redox-stimulated pathways likely represent a conserved mechanism by which the host interacts with its commensal microbiota, and thus presents an attractive target for therapeutic manipulation.

总结/摘要 胃肠道粘膜作为腔内容物和下层组织之间的界面起作用 因此，它在维持粘膜和全身稳态中至关重要。肠腔容纳了 数量庞大且分类多样的原核微生物群。在健康状态下，粘膜和微生物群茁壮成长， 在一个互利的共生安排。宿主和微生物都进化出了一个复杂的系统， 相互感知、反应和反应。这些事件部分是由肠道的能力介导的， 上皮细胞通过产生活性氧（ROS）对微生物群的特定成员作出反应， 其用于激活参与维持肠道内稳态的多种细胞途径。这项建议 将采用体内系统，包括广泛使用无菌小鼠，或用 已知的ROS诱导细菌。此外，新生小鼠中微生物群的分类学分析将用于 识别对肠道粘膜具有功能影响的其他细菌。该提案将研究微生物对 已知的和新的信号传导途径，并表征对肠道存活，分化和 增殖我们的总体目标是定义参与者、事件和过程， 宿主微生物接触以及这种相互作用如何影响肠道内稳态、发育和 赔偿ROS和氧化还原刺激途径可能代表了一种保守的机制， 与其肠道微生物群相互作用，因此为治疗操作提供了有吸引力的靶标。

项目成果

Interactions Between Commensal Bacteria and Enteric Neurons, via FPR1 Induction of ROS, Increase Gastrointestinal Motility in Mice.

• DOI: 10.1053/j.gastro.2019.03.045
• 发表时间: 2019-07
• 期刊: Gastroenterology
• 影响因子: 29.4
• 作者: Chandrasekharan B;Saeedi BJ;Alam A;Houser M;Srinivasan S;Tansey M;Jones R;Nusrat A;Neish AS
• 通讯作者: Neish AS

Redox control of Cas phosphorylation requires Abl kinase in regulation of intestinal epithelial cell spreading and migration.

Cas 磷酸化的氧化还原控制需要 Abl 激酶来调节肠上皮细胞的扩散和迁移。

• DOI: 10.1152/ajpgi.00189.2016
• 发表时间: 2016
• 期刊: American journal of physiology. Gastrointestinal and liver physiology
• 作者: Matthews,JasonD;Sumagin,Ronen;Hinrichs,Benjamin;Nusrat,Asma;Parkos,CharlesA;Neish,AndrewS
• 通讯作者: Neish,AndrewS

Imaging the Gut with "CLARITY".

• DOI: 10.3791/62143
• 发表时间: 2021-06-11
• 期刊: Journal of visualized experiments : JoVE
• 作者: Chandrasekharan B;Neish AS
• 通讯作者: Neish AS

Redox signaling mediates symbiosis between the gut microbiota and the intestine.

氧化还原信号介导肠道微生物群和肠道之间的共生。

• DOI: 10.4161/gmic.27917
• 发表时间: 2014
• 期刊: Gut microbes
• 影响因子: 12.2
• 作者: Neish,AndrewS;Jones,RheinalltM
• 通讯作者: Jones,RheinalltM

Proteomic analysis of microbial induced redox-dependent intestinal signaling.

• DOI: 10.1016/j.redox.2018.11.011
• 发表时间: 2019-01
• 期刊: Redox biology
• 影响因子: 11.4
• 作者: Matthews JD;Reedy AR;Wu H;Hinrichs BH;Darby TM;Addis C;Robinson BS;Go YM;Jones DP;Jones RM;Neish AS
• 通讯作者: Neish AS