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Interpersonal variation in microbiome structure modulates inter-individual immune responses to Vibrio cholerae

微生物组结构的人际差异调节个体间对霍乱弧菌的免疫反应

基本信息

批准号：
10750525
负责人：
Elyza Amber Do
金额：
$ 4.02万
依托单位：
UNIVERSITY OF CALIFORNIA RIVERSIDE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-12-26 至 2026-12-25
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10750525
关键词：
Antibody Response Area Automobile Driving CD4 Positive T Lymphocytes Case Fatality Rates Cells Cessation of life Characteristics Cholera Cholera Vaccine Collection Communities Data Dehydration Development Diarrhea Diet Economics Epidemic Etiology Exposure to Gastrointestinal tract structure Geographic Locations Geography Germ-Free Gnotobiotic Goals Gram-Negative Bacteria Health Priorities Human Hypovolemic Shock Immune Immune response Immune system Immunity Immunization Immunology Immunophenotyping Impairment Individual Individual Differences Indonesia Infection Intestines Lead Left Malnutrition Mediating Mentorship Microbe Microbiology Modeling Morbidity - disease rate Mus Nature Oral Oral Rehydration Therapy Outcome Output Peripheral Population Predisposition Probiotics Prophylactic treatment Regulatory T-Lymphocyte Resolution Role Shapes Structure System Testing Therapeutic Transplantation Vaccination Variant Vibrio cholerae Vibrio cholerae infection Vomiting Work diarrheal disease dysbiosis enteric infection enteric pathogen global health gut microbiota host microbiota human microbiota improved insight inter-individual variation interest member microbial microbial community microbial composition microbiome microbiome composition microbiota mouse model mucosal vaccination mucosal vaccine novel oral vaccine prebiotics prophylactic protective efficacy response vaccination outcome vaccine efficacy vaccine response volunteer

项目摘要

PROJECT SUMMARY Vibrio cholerae is a Gram-negative bacterium and the etiologic agent of cholera, a severe human diarrheal disease characterized by voluminous watery diarrhea and vomiting and when left untreated, severe dehydration, hypovolemic shock, and death. Several oral cholera vaccines (OCV) have been developed but demonstrate variable efficacy in distinct geographical regions. Thus, defining the factors that modulate such variation and developing strategies to minimize variability in prophylactic efficacy remains a significant global health priority. One host-associated factor that has demonstrated differences in composition and functional output between populations of high and low OCV efficacy is the commensal microbial community of the gastrointestinal tract, the gut microbiota. Our central hypothesis is that interpersonal variation in the microbial community of the gastrointestinal tract contributes to significant interpersonal variation in OCV responses caused by microbe-specific modulation of the intestinal immune system. Our preliminary data suggest that the gut microbiota may acts a personalized contributor to oral cholera vaccination outcome, whereby (i) specific microbial taxa correlate with distinct immune responses to oral cholera vaccination; (ii), inter-individual variation in microbiota structure and (iii) dysbiotic microbiotas, representative of gut microbial communities found in cholera endemic areas, directly influence infection and vaccination outcomes to V. cholerae; and (iv) modulation of host intestinal CD4+ T-cells regulate host immune responses to V. cholerae challenge. Precision editing of the gut microbiota may represent an effective strategy to enhance oral vaccine responsiveness, but such approaches will require a detailed understanding of the specific microbe(s) involved and the particular mechanisms by which they enhance or inhibit human immunophenotypes of interest, particularly in the context of oral vaccine responses. Our ultimate goal is to identify specific microbial taxa that drive differential immune responses to V. cholerae, as such candidates may better inform the development of gut microbiota-targeted prebiotic and probiotic strategies for cholerae prophylaxis. We will address this problem with the following study aims: Aim 1 - Determine the effect of inter- individual microbiota variation on OCV responsiveness; Aim 2 - Define immune cell populations that mediate microbiota-driven effects on OCV responses.

项目总结