Assessing feeding practices, immune activation, and HIV risk in African infants

描述(申请人提供)：母乳喂养可占儿童艾滋病毒感染的39%。在发达国家，感染艾滋病毒的母亲给婴儿喂配方奶粉，以防止产后艾滋病毒传播。然而，在发展中国家的许多地区，人们买不起配方奶粉，而且由于胃肠炎和营养不良等传染病，婴儿配方奶粉的发病率和死亡率很高。因此，目前的世卫组织指南建议来自大多数不发达地区的感染艾滋病毒的母亲用母乳喂养婴儿。多项观察性、前瞻性研究表明，与除母乳外还与其他牛奶、液体或固体混合喂养(MF)的婴儿相比，纯母乳喂养(EBF)可将母婴传播(MTCT)的风险降低两到十倍。EBF降低了发病率，即使在发达和发展中环境中未接触艾滋病毒的婴儿中也是如此。EBF降低了发病率，即使在发达和发展中环境中未接触艾滋病毒的婴儿中也是如此。然而，EBF对母亲来说很难维持，婴儿在四到六个月大后会得到补充食物。此外，一项在4个月时快速断奶的EBF研究显示，未感染婴儿的发病率很高。了解与这种风险增加相关的机制可能导致采取干预措施，使混合喂养和补充喂养对婴儿更安全。EBF的保护作用的一个潜在解释是，添加非母乳液体和固体改变了婴儿上胃肠道的粘膜或免疫屏障。这可能会导致免疫细胞激活，粘膜上的HIV靶细胞增加，或者肠道内微生物移位增加，这可能是由于粘膜完整性受损或胃肠道和/或全身感染增加所致。该项目通过测量不同喂养方式的婴儿血液和唾液中的免疫活性，测试了这样一种假设，即与EBF婴儿(目标1)相比，混合喂养的婴儿将在粘膜和系统间隔内显示出免疫激活的证据。这种免疫活性的增加可能是由于早期生命中肠道共生生物体的变化(目标2)。因此，这些实验将分析这些婴儿粪便中的微生物。这种激活可能源于混合喂养引起的粘膜损伤或感染，以及随之而来的细菌产物通过肠道粘膜进入体循环(目标3)，因此我们的实验将测量血液中的微生物产物。通过在多个时间点(6周和14周)对这些婴儿进行评估，这项研究计划评估使EBF婴儿降低艾滋病毒感染风险的机制，并揭示混合喂养期间母婴传播预防的目标，并潜在地使全球所有无法EBF的婴儿受益。

DESCRIPTION (provided by applicant): Breastfeeding can account for up to 39% of pediatric HIV infections. In developed countries, HIV-infected mothers feed formula to their infants to prevent postpartum HIV transmission. However, in many parts of the developing world, formula is unaffordable and is associated with high morbidity and mortality due to infectious diseases such as gastroenteritis and malnourishment. Therefore, the current WHO guidelines recommend that HIV-infected mothers from most underdeveloped settings breastfeed their infants. Multiple observational, prospective studies have shown that exclusive breastfeeding (EBF) reduces the risk of mother-to-child- transmission (MTCT) two to tenfold compared to infants that are mixed-fed (MF) with other milks, liquids, or solids in addition to breast. EBF decreases morbidity even in non-HIV-exposed infants in both developed and developing settings. EBF decreases morbidity even in non-HIV-exposed infants in both developed and developing settings. However, EBF is difficult for mothers to maintain, and infants are given complementary foods after four to six months of age. In addition, a study of EBF with rapid weaning at four months showed high morbidity in the uninfected infants. Understanding the mechanisms associated with this increased risk could lead to interventions to make mixed feeding and complementary feeding safer for infants. One potential explanation for the protective effect of EBF is that the addition of non-breast milk liquids and solids alters the infant's mucosal or immunologic barriers of the upper gastrointestinal tract. This could lead to immune cell activation with an increase HIV target cells at the mucosa, or increased microbial translocation across the gut, possibly due to compromised mucosal integrity or increased gastrointestinal and/or systemic infections. This project tests the hypothesis that mixed fed infants will display evidence for immune activation within both mucosal and systemic compartments when compared to EBF infants (Aim 1), by measuring immune activation in the blood and in saliva of infants with different feeding practices. This increase in immune activation could be due to changes in the gut commensal organisms in early life (Aim 2). Therefore, these experiments will analyze the microbes in stool of these babies. This activation is possibly derived from mixed feeding- induced mucosal impairment or infections and the consequent translocation of bacterial products across the gut mucosa into the systemic circulation (Aim 3), therefore our experiments will measure microbial products in blood. Through assessment of these infants at multiple time points (6 and 14 weeks of age), this study plans to evaluate the mechanisms conferring EBF infants a reduced risk of HIV infection, and to uncover targets for MTCT prevention during mixed feeding, and to potentially benefit all infants globally who cannot EBF.