Gonia Sara, Heisel Timothy, Miller Neely, Haapala Jacob, Harnack Lisa, Georgieff Michael K, Fields David A, Knights Dan, Jacobs Katherine, Seburg Elisabeth, Demerath Ellen W, Gale Cheryl A, Swanson Marie H
Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States.
Department of Psychology, University of Minnesota, Minneapolis, MN, United States.
Front Nutr. 2024 Sep 25;11:1456111. doi: 10.3389/fnut.2024.1456111. eCollection 2024.
Early life gut microbiomes are important for brain and immune system development in animal models. Probiotic use has been proposed as a strategy to promote health via modulation of microbiomes. In this observational study, we explore if early life exposure to probiotics via the mother during pregnancy and lactation, is associated with decreased inflammation in breastmilk, maternal and infant microbiome variation, and altered infant neurodevelopmental features.
Exclusively breastfeeding mother-infant dyads were recruited as part of the "Mothers and Infants Linked for Healthy Growth (MILk) Study." Probiotic comparison groups were defined by exposure to maternal probiotics (NO/YES) and by timing of probiotic exposure (prenatal, postnatal, total). C-reactive protein (CRP) and IL-6 levels were determined in breastmilk by immunoassays, and microbiomes were characterized from 1-month milk and from 1- and 6-month infant feces by 16S rDNA sequencing. Infant brain function was profiled via electroencephalogram (EEG); we assessed recognition memory using event-related potential (ERP) responses to familiar and novel auditory (1 month) and visual (6 months) stimuli. Statistical comparisons of study outcomes between probiotic groups were performed using permutational analysis of variance (PERMANOVA) (microbiome) and linear models (all other study outcomes), including relevant covariables as indicated.
We observed associations between probiotic exposure and lower breastmilk CRP and IL-6 levels, and infant gut microbiome variation at 1- and 6-months of age (including higher abundances of and ). In addition, maternal probiotic exposure was associated with differences in infant ERP features at 6-months of age. Specifically, infants who were exposed to postnatal maternal probiotics (between the 1- and 6-month study visits) via breastfeeding/breastmilk, had larger differential responses between familiar and novel visual stimuli with respect to the late slow wave component of the EEG, which may indicate greater memory updating potential. The milk of mothers of this subgroup of infants had lower IL-6 levels and infants had different 6-month fecal microbiomes as compared to those in the "NO" maternal probiotics group.
These results support continued research into "Microbiota-Gut-Brain" connections during early life and the role of pre- and postnatal probiotics in mothers to promote healthy microbiome-associated outcomes in infants.
在动物模型中，早期生命阶段的肠道微生物群对大脑和免疫系统发育至关重要。使用益生菌已被提议作为一种通过调节微生物群来促进健康的策略。在这项观察性研究中，我们探讨孕期和哺乳期经母亲早期接触益生菌是否与母乳中炎症减少、母婴微生物群变化以及婴儿神经发育特征改变有关。
作为“母婴健康成长关联研究（MILk研究）”的一部分，招募了纯母乳喂养的母婴对。益生菌比较组根据母亲益生菌暴露情况（无/有）和益生菌暴露时间（产前、产后、全程）来定义。通过免疫测定法测定母乳中的C反应蛋白（CRP）和白细胞介素-6（IL-6）水平，并通过16S核糖体DNA测序对1个月龄母乳以及1个月龄和6个月龄婴儿粪便中的微生物群进行特征分析。通过脑电图（EEG）对婴儿脑功能进行分析；我们使用事件相关电位（ERP）对熟悉和新颖的听觉（1个月）和视觉（6个月）刺激的反应来评估识别记忆。使用置换方差分析（PERMANOVA）（微生物群）和线性模型（所有其他研究结果）对益生菌组之间的研究结果进行统计比较，包括所示的相关协变量。
我们观察到益生菌暴露与较低的母乳CRP和IL-6水平以及1个月龄和6个月龄时婴儿肠道微生物群变化之间存在关联（包括 和 的丰度较高）。此外，母亲益生菌暴露与6个月龄时婴儿ERP特征的差异有关。具体而言，通过母乳喂养/母乳在产后（1个月至6个月研究访视期间）接触母亲益生菌的婴儿，在熟悉和新颖视觉刺激之间，脑电图的晚期慢波成分的差异反应更大，这可能表明更大的记忆更新潜力。与“无”母亲益生菌组相比，该亚组婴儿的母亲的母乳中IL-6水平较低，且婴儿6个月龄时的粪便微生物群不同。
这些结果支持继续研究早期生命阶段的“微生物群-肠道-大脑”联系以及产前和产后益生菌在母亲中的作用，以促进婴儿与微生物群相关的健康结局。
