The Effect of Processed Grain Consumption on the Dentogingival Microbiome and Host Response in Periodontal Disease

加工谷物消费对牙周病牙龈微生物组和宿主反应的影响

• 批准号: 10442422
• 负责人: Lea Maryam Sedghi
• 金额: $ 5.26万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10442422
• 关键词: 16S ribosomal RNA sequencing; Actinomyces; Address; Adoption; Affect; Alveolar Bone Loss; Amylases; Automobile Driving; Bacteria; Biological Availability; Bite Force; Carbohydrates; Cells; Communities; Complementary DNA; Consumption; Data; Debridement; Development; Diet; Digestion; Disease; Disease Progression; E-Cadherin; Epithelial Cells; Excision; Flow Cytometry; Fluorescent in Situ Hybridization; Food; Forsythia; Fusobacterium nucleatum; Gene Expression; Genetic Transcription; Gingiva; Grain; Growth; Harvest; Hydrolysis; Immune; Immune response; Immunity; Immunohistochemistry; In Vitro; Incidence; Infection; Inflammation; Inflammatory Response; Investigation; Mastication; Mechanics; Microbial Biofilms; Microfluidics; Modeling; Mus; Nutritional; Onset of illness; Oral; Oral cavity; Outcome; Periodontal Diseases; Periodontal Ligament; Phase; Physiological; Population; Porphyromonas gingivalis; Predisposition; Prevention; Process; Property; RNA; Roentgen Rays; Role; Salivary; Site; Soft Diet; Standardization; Starch; Streptococcus gordonii; Streptococcus sanguis; Structure; Surface; System; Texture; Tissues; Transcript; Transmission Electron Microscopy; Treponema denticola; Virulence; Western Blotting; Wheat; base; beta catenin; carbohydrate metabolism; dysbiosis; improved; in vivo; in vivo Model; light microscopy; mandible/maxilla; microCT; microbial; microbial colonization; microbiome; novel strategies; novel therapeutic intervention; novel therapeutics; oral microbial community; oral microbiome; particle; pathogen; periodontopathogen; polymicrobial biofilm; response; tomography; transcriptome sequencing; western diet

PROJECT SUMMARY/ABSTRACT Periodontal disease (PD) affects approximately 50% of the world population. Microbial dysbiosis and gingival inflammation are well-recognized in PD. However, the role of diet on these parameters is minimally explored. Increased PD incidence coincides with the adoption of the western diet that is characterized by consumption of highly processed, refined grains. Grain processing alters both nutritional and structural properties of grains via removal of the outer bran layer to isolate inner starch-rich components. This disrupts the integrity of the grain structure, resulting in increased starch bioavailability and finer grain texture. Refined grain consumption is associated with increased incidence of PD. However, the mechanisms by which refined grains increase PD incidence are unexplored. Digestion commences in the oral phase via starch hydrolysis by salivary amylase and mechanical digestion by mastication. Saccharides are made available to bacteria in the oral cavity via starch hydrolysis by salivary amylase. Increased saccharide availability alters microbial carbohydrate metabolism, driving microbial dysbiosis within dentogingival biofilm communities. Dentogingival surfaces provide an opportunity for mature microbial biofilm formation. Excess biofilm formation drives dysbiosis as successional colonization increases the representation of periodontal pathogens within the community. As such, mechanical debridement is required to disrupt biofilm formation. Increased diet texture has been shown to decrease biofilm accumulation. Moreover, increased masticatory forces by hard diets induce a protective inflammatory response in gingival tissues, consistent with the role of the gingiva as a physiological barrier. As grain processing increases starch bioavailability and its susceptibility to salivary amylase, this may increase saccharide availability to bacteria in the oral cavity and encourage dysbiosis. Moreover, as grain processing disrupts the integrity of the grain structure, such changes may reduce masticatory forces and thereby encourage excess microbial colonization and reduce gingival barrier function. Therefore, I hypothesize that processed grains induce PD progression by promoting microbial dysbiosis and/or by conferring reduced gingival barrier function via local influences within the oral cavity. This proposal will address my hypothesis via two specific aims: 1) Determine the impact of processed grains on development of multispecies dentogingival biofilms in vitro, and 2) Determine the impact of processed grains on the dentogingival microbiome, periodontal immune response, and gingival barrier function in vivo. These aims will be achieved utilizing a combination of in vitro and in vivo models to recapitulate changes in the dentogingival microbiome and periodontal immunity in response to processed grain consumption. Outcomes from this investigation will improve the understanding of the role of diet in PD progression and will create avenues for the development of novel therapeutic applications that leverage the oral microbiome for prevention of PD onset and progression.

项目概要/摘要 牙周病 (PD) 影响着世界大约 50% 的人口。微生物失调与牙龈 PD 中的炎症是众所周知的。然而，饮食对这些参数的作用却很少被探讨。 PD 发病率的增加与西方饮食的采用相一致，西方饮食的特点是食用 高度加工的精制谷物。谷物加工通过以下方式改变谷物的营养和结构特性： 去除外麸层以分离内部富含淀粉的成分。这破坏了谷物的完整性 结构，从而提高淀粉的生物利用度和更细的颗粒质地。精粮消费量为 与 PD 发病率增加有关。然而，精制谷物增加 PD 的机制 发病率尚未探索。消化在口腔阶段开始，通过唾液淀粉酶水解淀粉， 通过咀嚼进行机械消化。口腔中的细菌通过淀粉获得糖类 被唾液淀粉酶水解。糖类利用率的增加改变了微生物碳水化合物的代谢， 驱动牙龈生物膜群落内的微生物失调。牙龈表面提供 成熟微生物生物膜形成的机会。过度的生物膜形成会导致生态失调 定植增加了群落内牙周病原体的代表性。因此，机械 需要清创来破坏生物膜的形成。增加饮食结构已被证明可以减少生物膜 积累。此外，硬饮食增加的咀嚼力会诱导保护性炎症反应 在牙龈组织中，与牙龈作为生理屏障的作用一致。随着粮食加工量的增加 淀粉的生物利用度及其对唾液淀粉酶的敏感性，这可能会增加糖的利用度 口腔中的细菌并促进菌群失调。此外，由于谷物加工破坏了粮食的完整性 谷物结构，这种变化可能会降低咀嚼力，从而鼓励过量的微生物 定植并降低牙龈屏障功能。因此，我假设加工过的谷物会诱发 PD 通过促进微生物失调和/或通过降低牙龈屏障功能来进展 口腔内的局部影响。该提案将通过两个具体目标来解决我的假设：1） 确定加工谷物对体外多物种牙龈生物膜发育的影响，2) 确定加工谷物对牙龈微生物群、牙周免疫反应的影响，以及 体内牙龈屏障功能。这些目标将通过结合体外和体内模型来实现 概括牙龈微生物组和牙周免疫对加工后的反应的变化 粮食消费。这项调查的结果将提高人们对饮食在帕金森病中作用的理解 进展并将为开发利用口服药物的新型治疗应用创造途径 预防帕金森病发病和进展的微生物组。