Interplay between Dietary Fiber and Gut Microbiota in Hepatocellular Carcinoma

膳食纤维与肠道微生物群在肝细胞癌中的相互作用

基本信息

批准号：
10411391
负责人：
MATAM VIJAY-KUMAR
金额：
$ 5.93万
依托单位：
UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10411391
关键词：
Address Adult Adverse effects Affect Bacteria Biochemical Biological Cancer Etiology Carbon Cellulose Cessation of life Chronic Consumption Coupled Data Development Diagnosis Diet Dietary Component Dietary Fiber Dietary Intervention Dietary intake Disease Dose Edible Plants Energy-Generating Resources Enzymes Exhibits Fermentation Fiber Fibrosis Flagellin Food Food Additives Food Industry Formulation Functional disorder Funding Glucose Goals Health Hepatic Hepatitis High Fat Diet Homeostasis Human Immune Immunologic Receptors Incidence Infection Inulin Kinetics LCN2 gene Lignin Link Lipolysis Liver Malignant Neoplasms Metabolic Diseases Metabolic syndrome Metabolism Modeling Mus Mutant Strains Mice Natural Immunity Nature Nutritional Organism Pathogenesis Patients Pectins Phenotype Plants Play Polysaccharides Predisposition Primary carcinoma of the liver cells Property Public Health Publishing Recommendation Research Role Structure Supplementation TLR5 gene Time Translational Research Volatile Fatty Acids Work base dietary dysbiosis feeding firewall gastrointestinal epithelium gut dysbiosis gut health gut microbiota indexing inflammatory disease of the intestine insoluble fiber lipid biosynthesis microbiota mortality mouse model novel polyglucosan prebiotics protein metabolite soluble fiber theories therapeutic target tumorigenesis

项目摘要

Project Summary The overall goal of our research is to identify the mechanisms and factors/metabolite(s) by which dietary soluble fiber inulin induces hepatocellular carcinoma (HCC) in mice lacking toll-like receptor 5 (TLR5). TLR5, an innate immune receptor that senses bacterial flagellin, plays a critical role in gut microbiota homeostasis. Accordingly, TLR5 deficient mice display hallmarks of metabolic syndrome, which is absolutely microbiota dependent. This work aims to elucidate how a natural dietary component and widely used food additive drives HCC in innate immune deficient mice coupled with gut microbiotal overgrowth. Three specific aims are proposed, each of which investigates the mechanisms by which HCC develops in mice with gut dysbiosis. The three aims are interrelated, independently achievable and address the contributions of (i) structurally different natural soluble fibers, (ii) gut microbiota, and (iii) host hepatic lipogenesis/lipolysis to the development of HCC. This proposal has potential implications for public health, given the prevalent and overuse of inulin in the food industry. Our work would elucidate the underappreciated potential detrimental effects of inulin and/or SCFAs. Further, human HCC is the sixth most common cancer and third most cause of cancer related deaths globally. The higher mortality rates in patients with HCC are due to poor and late stage diagnosis because of its heterogeneous and asymptomatic nature. This warrants a novel, hepatocarcinogen independent model to better understand human HCC. This proposal seeks to fulfill this constraint.

项目概要我们研究的总体目标是确定机制和因素/代谢物膳食可溶性纤维菊粉诱发小鼠肝细胞癌（HCC）缺乏 Toll 样受体 5 (TLR5)。 TLR5，一种感知的先天免疫受体细菌鞭毛蛋白在肠道微生物群稳态中起着至关重要的作用。因此，TLR5 缺陷小鼠表现出代谢综合征的特征，这绝对是微生物群造成的依赖。这项工作旨在阐明天然饮食成分如何广泛应用使用过的食品添加剂与肠道一起导致先天性免疫缺陷小鼠患肝癌微生物过度生长。提出了三个具体目标，每个目标都进行调查肠道菌群失调小鼠发生 HCC 的机制。这三个目标是相互关联、可独立实现并在结构上解决 (i) 的贡献不同的天然可溶性纤维，(ii) 肠道微生物群，以及 (iii) 宿主肝脏脂肪生成/脂肪分解对 HCC 发展的影响。鉴于普遍存在的情况，该提案对公共卫生具有潜在影响食品工业中菊粉的过度使用。我们的工作将阐明那些被低估的问题菊粉和/或 SCFA 的潜在有害影响。此外，人类肝癌是第六位全球最常见的癌症和癌症相关死亡的第三大原因。越高 HCC 患者的死亡率是由于诊断不良和晚期造成的其异质性和无症状性。这需要一种新型的肝癌物质更好地了解人类 HCC 的独立模型。本提案旨在实现这一目标约束。

项目成果

期刊论文数量（26）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Dietary Additives and Supplements Revisited: The Fewer, the Safer for Liver and Gut Health.

重新审视膳食添加剂和补充剂：越少，对肝脏和肠道健康越安全。

DOI：
发表时间：
2019
期刊：
影响因子：
0
作者：
Golonka, Rachel;Yeoh, Beng San;Vijay
通讯作者：
Vijay

Enterobactin induces the chemokine, interleukin-8, from intestinal epithelia by chelating intracellular iron.

肠杆菌素通过螯合细胞内铁，从肠上皮诱导趋化因子白细胞介素 8。

DOI：
发表时间：
2020
期刊：
影响因子：
12.2
作者：
Saha, Piu;Yeoh, Beng San;Xiao, Xia;Golonka, Rachel M;Abokor, Ahmed A;Wenceslau, Camilla F;Shah, Yatrik M;Joe, Bina;Vijay
通讯作者：
Vijay

Fermentable fiber-induced hepatocellular carcinoma in mice recapitulates gene signatures found in human liver cancer.

可发酵纤维诱导的小鼠肝细胞癌重现了人类肝癌中发现的基因特征。

DOI：
发表时间：
2020
期刊：
影响因子：
3.7
作者：
Chandrashekar, Darshan Shimoga;Golonka, Rachel M;Yeoh, Beng San;Gonzalez, David J;Heikenwälder, Mathias;Gerwirtz, Andrew T;Varambally, Sooryanarayana;Vijay
通讯作者：
Vijay

Reconstitution of the host holobiont in germ-free born male rats acutely increases bone growth and affects marrow cellular content.

在无菌出生的雄性大鼠中重建宿主全生物体会急剧增加骨骼生长并影响骨髓细胞含量。

DOI：
发表时间：
2021-12-01
期刊：
影响因子：
4.6
作者：
Czernik, Piotr J;Golonka, Rachel M;Chakraborty, Saroj;Yeoh, Beng San;Abokor, Ahmed A;Saha, Piu;Yeo, Ji;Mell, Blair;Cheng, Xi;Baroi, Sudipta;Tian, Yuan;Patterson, Andrew D;Joe, Bina;Vijay;Lecka
通讯作者：
Lecka

Eat more natural dietary fiber and whole grains to minimize liver disease risk.

多吃天然膳食纤维和全谷物，以尽量减少肝病风险。