Gut Bacteriophage Correspondence with Inflammation and Clinical Dietary Interventions

肠道噬菌体与炎症和临床饮食干预的对应关系

• 批准号: 10614428
• 负责人: Andrew Wallace Brooks
• 金额: $ 7.18万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10614428
• 关键词: Address; Affect; Age; American; Bacteria; Bacterial Model; Bacteriophages; Biological Markers; Blood; Body mass index; Capsid Proteins; Cell Differentiation process; Chronic; Chronic Disease; Clinic; Clinical; Clinical Trials; Colitis; Colorectal Cancer; Communities; DNA; Data Set; Diabetes Mellitus; Diet; Dietary Intervention; Disease; Environment; Ethnic Origin; Feces; Fellowship; Fiber; Foundations; Gastrointestinal Diseases; Gastrointestinal tract structure; Genome; Genomics; Genotype; Growth; Health; Human; Immune; Immune response; Immunity; Immunologic Markers; Individual; Infection Control; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Inflammatory Response; Intervention; Investigation; Length; Lipopolysaccharides; Lysogeny; Lytic; Lytic Phase; Measures; Mediating; Menstruation; Mentors; Mentorship; Metabolic; Metabolism; Metagenomics; Microbe; Modeling; Nature; Nutrient; Nutrient availability; Participant; Peptides; Periodicity; Pharmaceutical Preparations; Phenotype; Physiological; Play; Population; Positioning Attribute; Probiotics; Productivity; Prophages; Records; Recurrence; Research; Resolution; Role; Sampling; Shapes; Supplementation; Taxonomy; Time; Training; United States National Institutes of Health; Universities; Validation; Vertical Disease Transmission; career; cohort; collaborative environment; cost; cytokine; dietary; expectation; experience; fecal microbiome; fecal transplantation; gastrointestinal; gastrointestinal epithelium; gut bacteria; gut inflammation; gut microbiome; inflammatory marker; metabolome; metabolomics; metagenomic sequencing; microbial; microbiome; microbiome composition; multiple omics; particle; response; sex; success

Project Summary – NIH F32 Fellowship – Andrew Brooks – P.I. Mike Snyder Application Title: Gut Bacteriophage Correspondence with Inflammation and Clinical Dietary Interventions Recurring gastrointestinal inflammation contributes to chronic non-transmissible diseases like diabetes, inflammatory bowel disease, and colorectal cancer that afflict millions of Americans. A primary culprit is the gut microbiome, which is filled with trillions of bacteria and roughly as many predatory bacteriophages. Many gut phages are temperate, meaning they can cycle between dormant lysogenic prophages and active lytic phage particles that attack bacterial hosts. There are many direct and indirect mechanisms through which lytic phages trigger human immunity, yet whether those result in significant inflammatory responses is unknown. Therefore, it is critical to investigate the hypothesis that phages periodically contribute to gut inflammation during peaks in active lytic growth. Knowing whether phages significantly impact gut inflammation will be important as new evidence suggests phages are transmitted from mother to child, passed through fecal microbiome transplants, and persist within individuals for long periods. Phage persistence and growth are closely tied to availability of nutrients and bacterial hosts, and human diet shapes gut metabolites which in-turn affect bacteria in the microbiome. This suggests the second hypothesis, that dietary metabolites and their effects on gut bacteria can predict and shape phage activity. This project is well positioned to comprehensively address both aims by leveraging three temporal human studies within the Snyder lab and Stanford University which have proven research records instilling the foundations for productive academic careers. Participant samples are undergoing extensive multi’omic profiling (immunity, metabolism, genomics…), which will be related to gut phage and microbiome profiles generated using high throughput metagenomic sequencing. Immune profiles from blood and stool will quantify gut inflammation alongside metagenomic measures of gut phage activity. The expectation of the first hypothesis is that peaks in phage lytic activity will associate with increased inflammatory biomarkers. Two of the studies also involve clinical dietary interventions, providing controlled perturbation to address the second hypothesis that diet predicts and shapes phage activity. The expectation is that profiles of gut metabolites and bacteria are predictive of phage activity, and therefore clinical dietary effects on gut metabolites and microbiomes can shape phage growth. Aims will be addressed in three multi’omic studies examining diverse aspects of human health. This facilitates comprehensive scientific validation in an expert collaborative environment supported by a robust mentorship team. Pursuit will provide a population scale examination of human gut phages in an unprecedented multi’omic context, while the first aim examines phage activity as a factor in America’s most burdensome gastrointestinal diseases, and the second examines diet as a means to predict and shape that gut phage activity.

项目摘要 – NIH F32 奖学金 – Andrew Brooks – P.I. 申请标题：肠道噬菌体与炎症和临床饮食干预的对应关系 反复出现的胃肠道炎症会导致糖尿病等慢性非传染性疾病， 困扰数百万美国人的炎症性肠病和结直肠癌的罪魁祸首是肠道。 微生物组，充满了数万亿个细菌和大约与许多肠道一样多的掠食性噬菌体。 噬菌体是温和的，这意味着它们可以在休眠的溶原性噬菌体和活跃的裂解噬菌体之间循环 攻击细菌宿主的颗粒有许多直接和间接的机制。 触发人体免疫力，但是否会导致显着的炎症反应尚不清楚。 研究噬菌体周期性地导致肠道炎症的假设至关重要 了解噬菌体是否显着影响肠道炎症很重要。 新证据表明噬菌体通过粪便微生物群从母亲传给孩子 移植并在个体体内长期存在与噬菌体的持久性和生长密切相关。 营养物质和细菌宿主的可用性，以及人类饮食塑造肠道代谢，进而影响细菌 这表明了第二个假设，即饮食代谢物及其对肠道的影响。 细菌可以预测和塑造噬菌体活动。 该项目处于有利地位，可以通过利用三个时间人类来全面实现这两个目标 斯奈德实验室和斯坦福大学的研究已经证明了研究记录灌输了 参与者样本正在进行广泛的多组学分析。 （免疫、新陈代谢、基因组学……），这将与使用生成的肠道噬菌体和微生物组概况相关 高通量宏基因组测序将量化肠道炎症。 与肠道噬菌体活性的宏基因组测量一起，第一个假设的预期是峰值。 噬菌体溶解活性与炎症生物标志物增加有关，其中两项研究还涉及临床。 饮食干预，提供受控扰动来解决饮食预测和 预期肠道代谢物和细菌的特征可以预测噬菌体的活性。 活性，因此临床饮食对肠道代谢物和微生物组的影响可以影响噬菌体的生长。 将通过三项多组学研究来探讨人类健康的各个方面。 在强有力的指导支持下，在专家协作环境中进行全面的科学验证 Pursuit 团队将以前所未有的多组学方式对人类肠道噬菌体进行群体规模的检查。 背景，而第一个目标是检查噬菌体活性作为美国最负担重的胃肠道的一个因素 疾病，第二个研究饮食作为预测和塑造肠道噬菌体活动的手段。

项目成果

Pre-symptomatic detection of COVID-19 from smartwatch data.

根据智能手表数据对 COVID-19 进行症状前检测。

• 发表时间: 2020
• 影响因子: 28.1
• 作者: Mishra, Tejaswini;Wang, Meng;Metwally, Ahmed A;Bogu, Gireesh K;Brooks, Andrew W;Bahmani, Amir;Alavi, Arash;Celli, Alessandra;Higgs, Emily;Dagan;Fay, Bethany;Kirkpatrick, Susan;Kellogg, Ryan;Gibson, Michelle;Wang, Tao;Hunting
• 通讯作者: Hunting

Real-time alerting system for COVID-19 and other stress events using wearable data.

使用可穿戴数据针对 COVID-19 和其他压力事件的实时警报系统。

• 发表时间: 2022-01
• 影响因子: 82.9
• 作者: Alavi, Arash;Bogu, Gireesh K;Wang, Meng;Rangan, Ekanath Srihari;Brooks, Andrew W;Wang, Qiwen;Higgs, Emily;Celli, Alessandra;Mishra, Tejaswini;Metwally, Ahmed A;Cha, Kexin;Knowles, Peter;Alavi, Amir A;Bhasin, Rajat;Panchamukhi, Shrinivas;Cel
• 通讯作者: Cel