Gut microbiome evolution among HIV-exposed uninfected infants in Botswana

博茨瓦纳暴露于艾滋病毒的未感染婴儿的肠道微生物组进化

• 批准号: 8992961
• 负责人: Kathleen Powis
• 金额: $ 23.17万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8992961
• 关键词: Bacterial Translocation; Biological; Birth; Botswana; Breast Feeding; Child; Child Mortality; Cohort Studies; Country; Data; Development; Enrollment; Enteral; Evolution; Feces; HIV; HIV-exposed uninfected infant; Human Milk; Immune; Immune system; Immunocompromised Host; Immunologic Markers; Infant; Infant Mortality; Inflammatory; Life; Measures; Morbidity - disease rate; Mothers; Necrotizing Enterocolitis; Pathway interactions; Perinatal Exposure; Population; Postpartum Period; Premature Infant; Prevention; Principal Investigator; Probiotics; Public Health; Research; Resources; Systems Development; T-Lymphocyte; Vagina; Vulnerable Populations; Woman; base; cohort; cytokine; demographics; experience; gut microbiota; immune activation; immune function; infancy; microbiome; microorganism; modifiable risk; mortality; novel; prevent; programs; public health priorities; public health relevance; rectal; scale up; transmission process

 DESCRIPTION (provided by applicant): HIV-exposed uninfected (HEU) infants in resource-limited settings experience higher morbidity and mortality from infectous casuses compared with infants born to HIV-uninfected women, suggesting an immune dysregulation despite remaining HIV-uninfected. In infancy, immune system function and development are reliant upon the evolution of gut microbiota. However, this evolution, along with its impact on the immune system, has not been studied among HEU infants. Dysbiosis in the evolution of gut microbiota among HEU infants may be a significant contributor to higher HEU infant and child mortality. With the HEU population expanding at over 1 million infants per year in resouce-limited settings, it is of great public health importance to identify biologically plausible, modifiable risk factorsfor higher mortality. The aims of this study Botswana based study are: 1. To describe the evolution of the gut microbiome at birth, 3, 6, 9, and 12 months of life among 40 HEU breastfed infants compared with 40 HUU breastfed infants. 2. To assess for differences in innate and adaptive immune function and soluble markers of immune activation at 3, 6, and 9 months of life between HEU and HUU infants and correlate immune profiles with enteric microbiota profiles. 3. Among HIV-infected and HIV-uninfected mothers, to compare vaginal, rectal and breast milk microbiome at delivery, and breast milk microbiome 1 month postpartum, between HIV- infected and HIV-uninfected mothers of infants enrolled in the study.

 描述（由申请人提供）：与未感染艾滋病毒的妇女所生婴儿相比，资源有限环境中暴露于艾滋病毒的未感染（HEU）婴儿因感染原因的发病率和死亡率更高，表明尽管未感染艾滋病毒，但仍存在免疫失调。在婴儿期，免疫系统功能和发育依赖于肠道微生物群的进化。然而，这种演变，沿着其对免疫系统的影响，尚未在高浓缩铀婴儿中进行研究。高浓缩铀婴儿肠道微生物群演变过程中的生态失调可能是高浓缩铀婴儿和儿童死亡率较高的一个重要原因。随着资源有限的环境中高浓缩铀人口以每年超过100万婴儿的速度增长，确定生物学上合理的、可改变的导致更高死亡率的风险因素对于公共卫生具有重要意义。本研究的目的博茨瓦纳为基础的研究是：1。描述40名HEU母乳喂养婴儿在出生时、出生后3个月、6个月、9个月和12个月时肠道微生物组的演变，并与40名HUU母乳喂养婴儿进行比较。2.评估HEU和HUU婴儿在出生后3个月、6个月和9个月时先天性和适应性免疫功能以及免疫激活的可溶性标志物的差异，并将免疫特征与肠道微生物群特征相关联。3.在HIV感染和未感染HIV的母亲中，比较分娩时的阴道、直肠和母乳微生物组，以及研究中入组婴儿的HIV感染和未感染HIV的母亲产后1个月的母乳微生物组。