Data_Sheet_1_Zinc Deficiency During Pregnancy Leads to Altered Microbiome and Elevated Inflammatory Markers in Mice.PDF

Zinc is an essential trace metal for bacteria of the intestinal flora. Approximately 20% of dietary zinc – intake is used by intestinal bacteria. The microbiome has recently been described as an important factor for healthy brain function via so-called gut-brain interactions. Similarly, zinc deficiency has been associated with neurological problems such as depression, mental lethargy and cognitive impairments in humans and animal models. However, the underlying pathomechanisms are currently not well understood and a link between zinc deficiency and altered microbiota composition has not been studied. Especially during pregnancy, women may be prone to low zinc status. Thus, here, we investigate whether zinc deficiency alters gut-brain interaction in pregnant mice by triggering changes in the microbiome. To that end, pregnant mice were fed different diets being zinc-adequate, deficient in zinc, or adequate in zinc but high in zinc uptake antagonists for 8 weeks. Our results show that acute zinc-deficient pregnant mice and pregnant mice on a diet high in zinc uptake antagonists have an altered composition of gastro-intestinal (GI) microbiota. These changes were accompanied by alterations in markers for GI permeability. Within the brain, we found signs of neuroinflammation. Interestingly, microbiota composition, gut pathology, and inflammatory cytokine levels were partially rescued upon supplementation of mice with zinc amino-acid conjugates (ZnAA). We conclude that zinc deficiency may contribute to abnormal gut-brain signaling by altering gut physiology, microbiota composition and triggering an increase of inflammatory markers.

锌（Zinc）是肠道菌群细菌必需的微量金属元素。膳食锌摄入中约有20%可供肠道细菌利用。近年来，肠道微生物组被认为是通过所谓的肠-脑交互（gut-brain interactions）调控健康脑功能的关键因素。类似地，在人类及动物模型中，锌缺乏已被证实与抑郁、精神倦怠及认知障碍等神经系统病症相关。然而，其潜在的病理生理机制目前尚未完全阐明，且锌缺乏与微生物组组成改变之间的关联尚未得到研究。尤其在妊娠期，女性往往易出现锌水平低下的状况。因此，本研究旨在探究锌缺乏是否通过改变肠道微生物组组成，进而影响孕鼠的肠-脑交互功能。为此，我们将孕鼠分为三组，分别饲喂锌充足饲料、锌缺乏饲料，以及锌充足但锌摄取拮抗剂含量较高的饲料，持续8周。研究结果显示，急性锌缺乏孕鼠以及饲喂高锌摄取拮抗剂饲料的孕鼠，其胃肠道（gastro-intestinal, GI）菌群组成均发生改变。此类改变同时伴随胃肠道通透性标志物的异常变化。在脑组织中，我们观察到神经炎症的相关征象。有趣的是，通过给小鼠饲喂锌氨基酸缀合物（zinc amino-acid conjugates, ZnAA）进行补充后，微生物组组成、肠道病理状况以及炎性细胞因子水平均得到部分恢复。我们得出结论：锌缺乏可能通过改变肠道生理状态、破坏微生物组组成，并触发炎性标志物水平升高，从而导致异常的肠-脑信号传导。