Marine Omega-3 Polyunsaturated Fatty Acid, Gut Microbiome, and Colorectal Cancer Prevention

海洋 Omega-3 多不饱和脂肪酸、肠道微生物组和结直肠癌预防

• 批准号: 9762057
• 负责人: Mingyang Song
• 金额: $ 18.18万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-19 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9762057
• 关键词: Adult; Alkaline Phosphatase; Anti-inflammatory; Area; Award; Bacteria; Bifidobacterium; Bioinformatics; Biological; Biological Markers; CD8-Positive T-Lymphocytes; Cell Maturation; Cells; Clinic; Colon; Colorectal Adenoma; Colorectal Cancer; Cues; Data; Data Aggregation; Dendritic Cells; Development; Diet; Dietary Component; Dietary Fats; Dietary Intervention; Docosahexaenoic Acids; Eicosapentaenoic Acid; Environment; Epidemiologist; Epidemiology; Excision; Fatty Acids; Feces; Fish Oils; Foundations; Fusobacterium nucleatum; Future; Gene Expression; Gene Expression Profiling; Genes; Grant; Homeostasis; Human; Hydroxyl Radical; Immune; Immune response; Immunity; Immunosuppressive Agents; Inflammatory; Intestines; Lactobacillus; Link; Lipopolysaccharides; Malignant Neoplasms; Marines; Mediating; Mediator of activation protein; Metabolic; Methods; Microbe; Mucous Membrane; Mus; Natural Products; Omega-3 Fatty Acids; Pathway interactions; Patients; Phase; Prevention therapy; Production; Property; Randomized Controlled Trials; Research; Research Personnel; Role; Shapes; Source; Structure; System; T cell response; Testing; Tissues; Training; Translating; Tumor Escape; Tumor Immunity; Tumor Tissue; Tumor-infiltrating immune cells; Volatile Fatty Acids; adenoma; anti-cancer; base; cancer immunotherapy; cancer initiation; cancer prevention; cancer therapy; carcinogenesis; career; career development; colorectal cancer prevention; colorectal cancer risk; design; docosapentaenoic acid; fatty acid supplementation; gut bacteria; gut microbes; gut microbiome; gut microbiota; host microbiota; immunoregulation; improved; innovation; insight; lipid mediator; metabolome; metabolomics; microbial; microbial community; microbiome research; microbiota; multiple omics; novel; novel marker; nutrition; preservation; pressure; programs; tumor; tumor progression

Fish oil, a rich source of marine omega-3 polyunsaturated fatty acids (MO3PUFAs), is the most popular natural product used by U.S. adults. Substantial data support the beneficial effect of MO3PUFAs on colorectal cancer (CRC) prevention and treatment. However, the specific mechanisms through which MO3PUFAs influence CRC are not well understood. Increasing evidence supports a pivotal role of gut microbes in integrating dietary cues with host immunity and potentially mediating the anticancer effect of MO3PUFAs. Dietary fat composition is a major driver of the gut microbial community structure. Mice fed with a high- MO3PUFA diet demonstrate increased abundance of the gut bacteria that support the host immunoprotective system and improve the efficacy of cancer immunotherapy, such as Bifidobacterium and Lactobacillus genera, and decreased abundance of the microbes that dampen antitumor immunity, such as Fusobacterium nucleatum, which has been shown to promote CRC by generating a tumor-permissive microenvironment. Taken together with my recent findings that the anti-CRC effect of MO3PUFAs is related to F. nucleatum abundance and immune infiltrates in tumor tissue, these data aggregately support the hypothesis that MO3PUFAs modulate the gut microbial composition and function to shape the gut immune response and suppress CRC. To test this hypothesis, I will perform a randomized controlled trial (RCT) in patients with prior adenoma by investigating the effect of MO3PUFA supplements on the gut microbiome, metabolome, and gene expression profiling in the colon. This innovative project will advance our understanding about the interplay between MO3PUFAs, gut microbiota, and host immunity in CRC. I am well suited to perform this research based on 1) my expertise in nutrition, epidemiology, quantitative methods, and biomarker research; 2) acquired training in the K99 phase on the gut microbiome, bioinformatics, and design and conduct of biomarker-based RCT; and 3) the unparalleled research environment to support my career development. Through this study, I will expand my expertise and develop a transdisciplinary research program as an independent investigator in the area of nutritional intervention, gut microbiome, and cancer prevention. The findings yielded from my research will uncover new biological mechanisms relating diet to carcinogenesis, and identify novel biomarkers or targets that can be effectively translated into the clinic to improve cancer prevention.

鱼油是海洋omega-3多不饱和脂肪酸（MO3PUFAS）的丰富来源，是最受欢迎的 美国成年人使用的天然产品。大量数据支持MO3PUFA对结直肠的有益效果 癌症（CRC）预防和治疗。但是，MO3PUFAS的特定机制 影响CRC并不理解。越来越多的证据支持肠道微生物在 将饮食线索与宿主免疫力相结合，并可能介导MO3PUFA的抗癌作用。 饮食脂肪成分是肠道微生物群落结构的主要驱动力。喂养高的小鼠 MO3PUFA饮食表明，支持宿主免疫保护的肠道细菌的丰度增加 系统并提高癌症免疫疗法的功效，例如双歧杆菌和乳酸杆菌 属的属，减少了抑制抗肿瘤免疫力的微生物，例如梭杆菌 Nucleatum，已显示通过产生肿瘤的微环境来促进CRC。 总而言之，我最近的发现是MO3PUFAS的抗CRC效应与F. nubleatum有关 肿瘤组织中的丰度和免疫浸润，这些数据总共支持以下假设。 MO3PUFA调节肠道微生物组成和功能，以塑造肠道免疫反应和 抑制CRC。为了检验该假设，我将对患有先验的患者进行随机对照试验（RCT） 通过研究MO3PUFA补充剂对肠道微生物组，代谢组和 结肠中的基因表达分析。这个创新的项目将提高我们对 CRC中的Mo3pufas，肠道微生物群和宿主免疫之间的相互作用。我非常适合执行此操作 基于1）我在营养，流行病学，定量方法和生物标志物研究方面的专业知识； 2）在肠道微生物组，生物信息学以及设计和行为的K99阶段获得了培训 基于生物标志物的RCT； 3）无与伦比的研究环境，以支持我的职业发展。 通过这项研究，我将扩大我的专业知识，并开发一个跨学科研究计划 营养干预，肠道微生物组和预防癌症领域的独立研究者。这 从我的研究中得出的结果将发现有关饮食与癌变有关的新生物学机制， 并确定可以有效地转化为诊所以改善癌症的新型生物标志物或靶标 预防。