Maternal stress and obesity alter milk immunobiology and impair infant growth

描述（由申请人提供）：来自人类和动物研究的证据表明，慢性应激暴露和肥胖协同作用，以提高循环应激和促炎信号。然而，对哺乳期母亲来说，不太清楚和特别重要的是，这些信号是否会转化为乳汁并影响婴儿发育。人乳含有许多激素和免疫信号，包括细胞因子、脂肪因子、免疫球蛋白（IG）和调节婴儿健康和发育的生长因子;然而，尚不清楚母亲压力和肥胖是否以及在多大程度上可能改变这些信号并产生婴儿的不良生长轨迹。由于压力源暴露和饮食是难以操纵的产后妇女，社会从属群体圈养恒河猴代表了一个翻译模型，以评估母亲的因素可能会影响牛奶免疫生物学和负面影响婴儿的生长和健康。为了从产后压力中分离出孕期母亲的压力，五十六名新生儿将被交叉寄养给相同或不同级别的母亲。此外，一半的母婴配对将在哺乳期保持低热量饮食，而另一半将切换到丰富的饮食条件。在整个哺乳期内，将对产妇护理、护理模式和社会地位进行行为评估。将通过自动喂食器监测断奶期间母亲和婴儿的摄食量。目标1将检验这一假设，即慢性社会压力和肥胖将协同增加牛奶中的压力和炎症信号。这一目标将通过测量不同社会等级（支配与从属）和产后饮食暴露（高热量与低热量）的泌乳恒河猴乳汁和血清中的皮质醇、细胞因子和脂肪因子标志物来实现。目的2：检验慢性社会压力和肥胖症会相互作用降低牛奶中免疫防御成分的假设。将与目标1中研究的应激和炎症标志物平行评价泌乳母鼠的sIgA乳汁水平。最后，目标3将确定目标1和2中研究的乳汁信号对婴儿生长和健康轨迹的贡献。具体来说，它将测试的假设，促炎细胞因子和脂肪因子显着预测婴儿的生长，除了丰富的饮食环境中的牛奶能量。总之，这项研究的结果将更好地定义母亲压力和肥胖引起的乳汁信号如何影响婴儿的生长和健康，这与NICHD的使命一致。此外，这项研究的结果将导致前瞻性研究，以确定哪些干预措施可以减轻产妇压力和肥胖对婴儿健康的不利影响。

DESCRIPTION (provided by applicant): Evidence from human and animal studies show that chronic stress exposure and obesity synergize to elevate circulating stress and pro-inflammatory signals. What is less clear and particularly important for nursing mothers, however, is whether these signals translate to milk and affect infant development. Human milk contains many hormonal and immunological signals including cytokines, adipokines, immunoglobulins (Ig), and growth factors that mediate infant health and development; however, it is not known whether and to what extent maternal stress and obesity may alter these and produce adverse growth trajectories for infants. Because stressor exposure and diet are difficult to manipulate in postpartum women, social subordination in group-housed rhesus macaques represents a translational model to assess how maternal factors may affect milk immunobiology and negatively impact infant growth and health. To disentangle prepartum maternal stress from postpartum stress, fifty-six newborns will be cross-fostered to mothers of the same or different ranks. In addition, half of the mother-infant dyads will be maintained on a low calorie diet through lactation while the other half will be switched to a rich dietary condition. Behavioral assessments of maternal care, nursing patterns, and social rank will be obtained throughout lactation. Food intake in the mothers and infants during weaning will be monitored through automated feeders. Aim 1 will test the hypothesis that chronic social stress and adiposity will synergize to increase stress and inflammatory signals in milk. This aim will be accomplished by measuring cortisol, cytokine and adipokine markers in milk and serum from lactating rhesus monkeys of different social rank (dominant vs. subordinate) and postpartum diet exposure (high calorie vs. low calorie). Aim 2 tests the hypothesis that chronic social stress and adiposity will interact to decrease immune defense components in milk. Milk levels of sIgA in lactating dams will be evaluated in parallel with stress and inflammatory markers studied in Aim 1. Finally, Aim 3 will determine the contribution of milk signals studied in aims 1 and 2 to infant growth and health trajectories. Specifically, it will test the hypothesis that pro-inflammatory cytokines and adipokines significantly predict infant growth in addition to milk energy in a rich dietary environment. Taken together, findings from this study will better define how milk signals induced by maternal stress and obesity may affect infant growth and health, consistent with the mission of NICHD. Furthermore, findings from this study will lead to prospective studies to determine what interventions alleviate these adverse effects of maternal stress and obesity on infant health.