Micronutrient deficiency (MND) (ie, lack of vitamins and minerals) during pregnancy is a major public health concern. Historically, studies have considered micronutrients in isolation; however, MNDs rarely occur alone. The impact of co-occurring MNDs on public health, mainly in shaping mucosal colonization by pathobionts from the family, remains undetermined due to lack of relevant animal models. To establish a maternal murine model of multiple MND (MMND), we customized a diet deficient in vitamins (A, B12, and B9) and minerals (iron and zinc) that most commonly affect children and women of reproductive age. Thereafter, mucosal adherence by , the associated inflammatory markers, and proteomic profile of intestines were determined in the offspring of MMND mothers (hereafter, low micronutrient [LM] pups) via bacterial plating, flow cytometry, and mass spectrometry, respectively. For human validation, abundance, assessed via 16s sequencing of 3-month-old infant fecal samples (n = 100), was correlated with micronutrient metabolites using Spearman’s correlation in meconium of children from the CHILD birth cohort. We developed an MMND model and reported an increase in colonic abundance of in LM pups at weaning. Findings from CHILD cohort confirmed a negative correlation between and micronutrient availability. Furthermore, pro-inflammatory cytokines and increased infiltration of lymphocyte antigen 6 complex high monocytes and M1-like macrophages were evident in the colons of LM pups. Mechanistically, mitochondrial dysfunction marked by reduced expression of nicotinamide adenine dinucleotide (NAD)H dehydrogenase and increased expression of () contributed to the bloom. This study establishes an early life MMND link to intestinal pathobiont colonization and mucosal inflammation via damaged mitochondria in the offspring.

中文翻译：

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母体微量营养素缺乏和后代肠道炎症宿主微生物相互作用的小鼠模型

怀孕期间的微量营养素缺乏（MND）（即缺乏维生素和矿物质）是一个主要的公共卫生问题。历史上，研究一直单独考虑微量营养素。然而，MND 很少单独发生。由于缺乏相关的动物模型，同时发生的 MND 对公共健康的影响（主要是影响家族中的致病生物在粘膜定植）的影响仍不确定。为了建立多发性运动神经元病 (MMND) 的母鼠模型，我们定制了缺乏维生素（A、B12 和 B9）和矿物质（铁和锌）的饮食，这些维生素最常影响育龄儿童和妇女。此后，分别通过细菌铺板、流式细胞术和质谱法测定 MMND 母亲的后代（以下简称低微量营养素 [LM] 幼崽）的粘膜粘附、相关炎症标记物和肠道蛋白质组谱。对于人体验证，通过对 3 个月大的婴儿粪便样本 (n = 100) 进行 16 秒测序评估，利用儿童出生队列中儿童胎便中的 Spearman 相关性，将丰度与微量营养素代谢物相关联。我们开发了一个 MMND 模型，并报告了断奶时 LM 幼崽的结肠丰度增加。儿童队列的研究结果证实，与微量营养素可用性之间存在负相关性。此外，在LM幼崽的结肠中，促炎细胞因子和淋巴细胞抗原6复合物高单核细胞和M1样巨噬细胞的浸润增加是明显的。从机制上讲，以烟酰胺腺嘌呤二核苷酸 (NAD)H 脱氢酶表达减少和 () 表达增加为标志的线粒体功能障碍导致了水华的发生。这项研究通过后代中受损的线粒体建立了生命早期 MMND 与肠道致病生物定植和粘膜炎症的联系。