Gut permeability and variations in bio-available vitamin D as mechanisms of adverse cognitive development in HIV-affected & control children - Anested Pilot Study

维生素D缺乏(VDD)在普通人群中很常见，尤其是在 生活在高海拔或日照有限地区的人以及艾滋病毒携带者 (公共卫生署)。VDD影响肠道微生物群和沿肠道-脑微生物区轴的紊乱 可能影响中枢神经系统(CNS)的动态平衡，改变先天和适应性 免疫系统，增加肠道通透性和微生物移位，使 肠道和血脑屏障渗漏。VDD也与更高的患病率相关 发育障碍，如自闭症谱系障碍(ASD)、注意力缺陷和多动症 儿童精神障碍(ADHD)和社会情绪适应能力差。在购物车中学习 接受治疗的人建议ART在潜在的治疗方案中进一步失调维生素D代谢组 依附时尚。对于感染了艾滋病毒但未感染的儿童，无论是围产期-ART 在敏感的发育窗口期暴露会导致长期的变化 维生素D代谢组对肠道微生物谱和神经发育的影响 弹道仍然未知。 我们正在进行的RO1研究旨在通过结合以下数据来开发认知风险指数(CRI 营养、免疫参数和HIV状态及其相互作用以验证CRI作为一种 12个月时神经认知障碍的预测因子。在这项初步研究中，我们收集了初步的 用于未来最终调查的数据，并通过调查艾滋病毒告知现有的知识差距 维生素D代谢组和肠道中与ART暴露相关的状态和早期失调 微生物失调是不良认知发展的可改变机制 易受伤害儿童的发育障碍风险。具体目标包括： A)使用代谢学方法评估维生素D代谢物，以量化相对丰度 各维生素D标准型(D2、D3)的生物活性形式。 B)评估肠道通透性的生物标志物及其与VDD和艾滋病毒状况的关系。 C)临床评估和诊断根据基线障碍概率选择的100名儿童 根据儿童行为评估系统估计的分数，第三版 (BASC3)和社会反应性量表，第二版。 总体影响：这些数据将提供初步数据，作为概念验证，以进一步 为更明确的变化机制研究建立科学的理论基础 维生素D代谢组和肠道微生物失调是不良反应的可修饰决定因素 乌干达感染艾滋病毒儿童和对照儿童的神经发育。

Vitamin D deficiency (VDD) is common in the general population, especially among people living in higher altitudes or areas with limited sunshine as well as persons living with HIV (PLWH). VDD impacts the gut microbiome and disturbances along the gut-brain microbiota axis may influence the central nervous system (CNS) homeostasis, alter innate and adaptive immune systems, and increase intestinal permeability and microbial translocation making the gut and blood-brain barriers leaky. VDD is also associated with higher prevalence of developmental disorders like autism spectrum disorder (ASD), attention deficit and hyperactivity disorder (ADHD), and poor socio-emotional adjustment in children. Studies among cART treated persons suggest ART further dysregulates vitamin D metabolome in potentially regimen dependent fashion. For children HIV exposed but uninfected, whether peripartum-ART exposure during sensitive developmental windows results in long-lasting changes in the metabolome of vitamin D with consequence for gut microbial profile and neurodevelopmental trajectory remains unknown. Our ongoing RO1 study aims to develop a Cognitive Risk Index (CRI) by combining data on nutrition, immune parameters and HIV status and their interactions to validate CRI as a predictor of neurocognitive disorders at 12 months. In this pilot study we collect preliminary data for future definitive investigations and inform existing knowledge gap by investigating HIV status and early ART exposure related dysregulations in vitamin D metabolome and gut- microbial dysbiosis as modifiable mechanisms of adverse cognitive development and developmental disorder risk in vulnerable children. Specific aims include: To a) Assess vitamin D metabolites using a metabolomic approach to quantify relative abundance of bioactive forms of the respective Vitamin-D canonical forms (D2, D3). b) Assess biomarkers of intestinal permeability and its relationship with VDD, and HIV status. c) Clinically evaluate and diagnose 100 children selected per baseline disorder probability scores estimated per the Behavioral Assessment System for Children, Third Edition (BASC3) and the social Responsiveness Scale, Second Edition. Overall Impact: This data will provide preliminary data that serves as proof of concept to further establish the scientific rationale for a more definitive mechanistic study of variations in the metabolome of vitamin D and gut-microbial dysbiosis as modifiable determinants of adverse neurodevelopment among Ugandan HIV-affected and control children.