Prenatal alcohol effects on the gut microbiome contributing to failure to thrive and altered immune function

胎儿酒精谱障碍(FASD)可包括不能归因于父母的生长缺陷 身高、胎龄或营养不良。最近对肠道微生物组的研究表明，肠道中的扰动 生命早期肠道细菌的种群动态可能会对宿主产生有害后果 包括无法茁壮成长，以及其他通常与一生营养不良有关的后遗症。其影响 微生物区系的改变可能会抵消通过改善营养来克服这些缺陷的努力。酒精 消费已被证明可以改变成人体内特定细菌属的比例。从新生儿开始 婴儿采用生母的菌群，很可能患有FASD的高危新生儿的肠道发生了变化 由于肠道细菌在加工过程中的重要性，微生物组最终会转化为营养不良 食品和产生饮食需求。肠道细菌在促进免疫方面也起着至关重要的作用。 动态平衡。细菌种群的变化可能会导致IL-25产生的下调较少，通过 上皮细胞和促炎性T细胞增多。肠道微生物群在FASD相关疾病中的作用 基于免疫学的疾病和无法蓬勃发展的问题一直没有得到充分的研究。我们假设新生的老鼠 与对照组相比，子宫内暴露于酒精的幼鼠在分娩时会产生肠道微生物区系的变化 这种改变的微生物区系将导致生长延迟和免疫失调。为了检验这一假说 我们建议1)比较长期饮酒前后雌性大鼠的肠道微生物区系， 并随着时间的推移分析它们幼崽的肠道微生物区系，以确定它们是否采用了母亲的菌群。 此外，我们将确定这种菌群是否与出生于控制水坝的幼崽不同 酒精。2)比较子宫内酒精暴露的幼崽和对照组幼崽的肠道免疫特征 确定酒精暴露是否会导致调节性免疫系统成分减少和 前炎性标志物和T细胞。3)确定与失败相关的肠道微生物区系中的细菌图谱 茁壮成长和/或免疫失调，并确定这些情况是否可以通过治疗来治疗 应用益生菌来匹配为控制水坝而出生的幼崽的结肠菌群。未来的研究可能 如果在动物身上的这些研究为临床提供了良好的前提，则很容易应用于人类受试者 调查。

Fetal Alcohol Spectrum Disorder (FASD) can include growth deficiency that is not attributable to parental height, gestational age, or poor nutrition. Recent studies on the gut microbiome indicate that perturbations in the population dynamics of the gut bacteria early in life can have deleterious consequences on the host including failure to thrive and other sequelae typically associated with poor nutrition throughout life. The impact of an altered microbiota can negate efforts to overcome these deficiencies with improved nutrition. Alcohol consumption has been demonstrated to alter the ratios of defined bacterial genera in adults. Since newborn babies adopt the flora of the birth mother, it is likely that neonates at high risk for a FASD have an altered gut microbiome that ultimately translates to poor nutrition given the importance of gut bacteria in processing certain food products and generating dietary needs. Gut bacteria also play a crucial role in promoting immunologic homeostasis. Alterations in bacterial populations may result in less down-regulatory IL-25 production by epithelial cells and increased proinflammatory T cells. The role of the gut microbiome in FASD associated immunological based diseases and failure to thrive has been understudied. We hypothesize newborn rats exposed to alcohol in utero will develop altered gut microbiota upon delivery compared to control rat pups and that this altered microbiota will contribute to delayed growth and immune dysregulation. To test this hypothesis we propose to 1) Compare the gut microbiota of female rats before and after chronic consumption of alcohol, and analyze the gut microbiota of their pups over time to determine if they adopt the flora of the mother. Additionally, we will determine if the flora is distinct from that of pups born to control dams not receiving alcohol. 2) Compare the intestinal immune features from pups exposed to alcohol in utero to control pups to determine if alcohol exposure results in reduced regulatory immune system elements and an increase in proinflammatory markers and T cells. 3) Identify bacterial profiles in the gut microbiota associated with failure to thrive and/or immune dysregulation and determine if these conditions can be treated by therapeutic application of probiotics designed to match the colonic flora of pups born to control dams. Future studies could readily be applied to human subjects if these studies in animals provide a sound premise for clinical investigation.