Gut microbiome evolution among HIV-exposed uninfected infants in Botswana

 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，在资源有限的环境中感染艾滋病毒的未感染(HEU)婴儿的发病率和死亡率更高，这表明尽管仍未感染艾滋病毒，但仍存在免疫调节失调。在婴儿期，免疫系统的功能和发育依赖于肠道微生物区系的进化。然而，这种进化及其对免疫系统的影响还没有在HEU婴儿中进行研究。HEU婴儿肠道微生物区系进化的失调可能是HEU婴儿和儿童死亡率较高的重要因素。在资源有限的环境下，随着每年100多万婴儿的HEU人口增长，确定生物学上看似合理的、可改变的危险因素是导致更高死亡率的重要公共卫生因素。本研究的目的是：1.描述40名HEU母乳喂养婴儿和40名HUU母乳喂养婴儿在出生时、3、6、9和12个月时肠道微生物组的演变。2.评估HEU和HUU婴儿出生后3、6、9个月的先天和获得性免疫功能以及免疫激活的可溶性标志物的差异，并将免疫模式与肠道微生物区系模式相关联。3.在HIV感染和未感染HIV的母亲中，比较研究中婴儿感染HIV和未感染HIV的母亲分娩时的阴道、直肠和母乳微生物组，以及产后1个月的母乳微生物组。

 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.