Commensal bacterial metabolism of dietary phytate in host defense

膳食植酸盐在宿主防御中的共生细菌代谢

• 批准号: 10738360
• 负责人: Seika Hashimoto-Hill
• 金额: $ 15.67万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10738360
• 关键词: Address; Bacteria; Bacterial Infections; Biology; Cessation of life; Child; Citrobacter rodentium; Collaborations; Communities; Coupled; Data; Development; Diet; Dietary Component; Dietary Factors; Disease; Environment; Enzymes; Epithelium; Fabaceae; Food; Formulation; Foundations; Future; Genes; Germ-Free; Gnotobiotic; Goals; Health; Host Defense; Host Defense Mechanism; Host resistance; Human; Immune response; Immunity; Immunology; Infection; Infection prevention; Inflammation; Ingestion; Inositol Phosphates; Intervention; Intestines; K-Series Research Career Programs; Knockout Mice; Knowledge; Link; Mammals; Mediating; Mentors; Metabolism; Metagenomics; Microbe; Modernization; Mouse Strains; Mucous Membrane; Mus; Natural Immunity; Nutrient; Nutritional; Nuts; Organoids; Phosphorus; Phytic Acid; Postdoctoral Fellow; Predisposition; Prevention; Recovery; Regulation; Research; Research Personnel; Role; STAT3 gene; Scientist; Technical Expertise; Testing; Training; Veterinarians; Work; antimicrobial peptide; bacterial metabolism; career; clinically relevant; commensal bacteria; cytokine; dietary; dietary approach; enteric infection; enteropathogenic Escherichia coli; host microbiota; immunoregulation; improved; infectious disease treatment; innovation; insight; interest; interleukin-22; intestinal epithelium; microbial; microbiota; mucosal site; novel; novel strategies; nutrient metabolism; nutrition; pathogenic bacteria; phytate; prevent; receptor; synergism; tool

Project summary/abstract Enteric infections remain highly prevalent worldwide with more than two billion cases and over one million deaths per year. Although diet has long been linked to infection susceptibility, the dietary factors that regulate intestinal defense remain poorly understood. In the intestine, there are trillions of microbes, collectively called the microbiota. Different diets can alter the composition and metabolites produced by these resident microbes in the intestine. In addition, recent work has highlighted clear links between microbiota colonization and effective immune responses at mucosal sites. Thus deciphering the interactions between diet, microbiota, and intestinal immunity will enable development of novel and practical dietary approaches to prevent and treat enteric infection. My new data provoke the hypothesis that metabolism of the nutrient phytate by commensal bacteria can decrease intestinal infection and boost host defense mechanisms. Studies outlined in this proposal will directly test this hypothesis by determining (i) how phytate-enriched diet enhances host intestinal defense in mouse and human intestine, and (ii) whether the microbiota is needed for phytate-mediated defense against intestinal infection. Delineating the contribution of diet and microbiota will significantly expand our understanding of mechanisms involved in intestinal immune regulation and inflammation. During my training as a veterinarian, I discovered my strong interest in understanding how the diet-microbiota relationship regulates intestinal infection. For this reason, I initiated the proposed project with Dr. Theresa Alenghat that will build upon my knowledge of mucosal immunology and enable me to transition into the fields of nutrition and microbiota. My thesis and initial postdoctoral work have provided me with an excellent foundation in immunology and epithelial biology, but I still lack technical skills and conceptual expertise in diet, gnotobiotics, metagenomic analyses, and human intestinal organoids. My mentors, Dr. Alenghat and Dr. James Wells, along with an exceptional scientific environment, will enable me to utilize modern, innovative approaches in my research and collaborate with top investigators. My understanding of disease in a broad range of species, coupled with my prior research, have provided me with a strong and unique foundation. Over the next five years, I fully anticipate that this background in conjunction with my current research plan will allow me to successfully carry out the proposed project. The mentoring and training I will receive from Dr. Alenghat and Dr. Wells, and from the wider Cincinnati Children’s community, will enable me to successfully transition into an independent scientist that can address clinically relevant questions at the interface of nutrition, microbiota, and infection.

项目总结/文摘