Impact of ethnicity in the gut microbiome in response to oral vitamin D replacement

摘要 由于维生素D缺乏对骨骼的不利影响以及与之相关的皮肤癌风险， 长期皮肤暴露于阳光下，口服补充维生素D3或D2已被广泛应用于 作为儿童和成人实现和维持钙稳态的模式被接受和推广。 鉴于最近对肠道微生物组对宿主人类健康的深远影响的认识， 疾病，与支持这一补充，我们将进行第一个试点研究，比较和对比， 最广泛使用的口服维生素D补充剂（维生素D3）与更快速起效的维生素D补充剂， 实验25-羟基化代谢物，25 D3，对肠道驻留的微生物，有第一次机会， 并对这些维生素D代谢物产生反应。 在这种补充剂的支持下，我们希望利用仍在招募的多种族维生素D 维生素D3和25-羟基维生素D3（25 D3）口服替代试验 母基金R 01 AR 063910的具体目标3中规定的缺陷受试者（血清总25 D ≤20 ng/ml）。 该申请包括在这些受试者中补充分析肠道微生物组的计划， 总血清和游离血清25 D正常化后。我们建议：i）在未来的时间里， 粪便微生物群的分类学16 S rRNA测序谱和2）改变的细菌的影响 微生物组对宿主的骨骼和免疫稳态的影响，这将由维生素D的形式调节 补充剂和宿主的种族（白色、黑人、西班牙裔、亚洲人）。这些新的分析将i） 补充已经资助的计划的新的测定技术，用于确定血清游离25 D和1，25 D 和ii）进一步推进我们对“个性化”维生素D健康的定义， 维生素D的非经典（免疫）作用。 !

ABSTRACT Owing to the adverse impact of vitamin D deficiency on the skeleton and risk of skin cancer associated with prolonged cutaneous exposure to sunlight, oral supplementation with vitamin D3 or D2 has been widely accepted and promoted as the mode of achieving and maintaining calcium homeostasis in children and adults. Given recent appreciation of the profound affect that the gut microbiome has on host human health and disease, with support of this supplement we will be performing the first pilot study to compare and contrast the impact of the most widely used oral vitamin D supplement (vitamin D3) versus the more rapidly acting, experimental 25-hydroxylated metabolite, 25D3, on the gut-residing microbes that have the first opportunity to encounter and respond to those vitamin D metabolites. With support from this supplement, we wish to take advantage of the still-recruiting, multi-ethnic vitamin D replacement trial comparing oral administration of vitamin D3 and 25-hydroxyvitamin D3 (25D3) in vitamin D deficient subjects (total serum 25D ≤20 ng/ml) set forth in Specific Aim 3 of the parent grant R01AR063910. This application includes a plan for supplemental analysis of the gut microbiome in those subjects before and after normalization of total and free serum 25D. We propose that i) there will exist predictable changes in the taxomic 16S rRNA-sequencing profiles of the stool microbiota and 2) the impact of that altered bacterial microbiome on the host's skeletal and immune homeostasis that will be conditioned by the form of vitamin D supplementation and the host's ethnicity (White, Black, Hispanic, Asian). These new analyses will i) compliment the already-funded program's novel assay technology for determining serum free 25D and 1,25D and ii) further advance our definition of `personalized' vitamin D health in terms of both classical (bone) and non-classical (immune) actions of vitamin D. !