Microbiome Core

项目总结/摘要：微生物核心 微生物组（MIBI）核心在HNRC中发挥着至关重要的作用，使研究人员能够调查 肠道微生物组、HIV、相关合并症和生物学机制之间新出现的复杂联系 涉及神经认知障碍（NCI）、情绪障碍和更复杂的神经行为表型 包括两者。近年来，肠道微生物组与神经系统和情绪密切相关 在个别研究中，尽管很少有研究将它们放在一起考虑，也没有研究将它们放在一起考虑。 艾滋病。特别是，关于HIV感染和ART如何影响肠道屏障功能障碍和中枢神经系统的问题， 从微生物组的角度来看，神经系统后遗症尚未得到很好的研究。然而，详细 关于微生物组如何参与抑郁症和2型糖尿病的机制解释，以及与 在非HIV背景下的病毒感染，强烈地激发了这样的研究。因此，MIBI的主要目标是 微生物组和代谢组技术广泛提供给HNRC研究人员，使我们能够超越 在上一个资助期内，NeuroGerm（NG）核心的16 S rRNA分析，并专注于微生物组- HIV感染者情绪和认知变化的相关机制（PWH）。提供超越 分类学分析，我们将使用先进的鸟枪宏基因组学技术来读出和组装细菌 以及来自粪便和血浆的病毒基因组，并将这些与来自非靶向代谢组学的化学谱相关联， 它还将捕获药物及其下游代谢物，并使我们能够将这些过程与 PWH中的微生物因为已知微生物组会受到宿主遗传学的影响，并且可能会相互作用， 由于病毒基因型和滴度，与其他核心的密切相互作用对于使研究人员能够 在这些需要复杂的多学科研究设计的问题上取得进展。此外，因为 高度多元的微生物组和代谢组数据的分析是具有挑战性的，MIBI的一个重要目标将是 提供生物信息学支持和培训，以了解如何将这些数据层相互整合， 临床数据对促进这些科学目标很重要。其结果将是更好地了解 微生物组影响并受长期HIV感染和合并感染的影响，以及微生物组和 代谢组学变化可能影响个体对HIV和相关疾病治疗的反应 （包括抑郁状态和NCI），并最终有助于改善长期战略 考虑到微生物组以减少长期合并症的艾滋病毒管理。

PROJECT SUMMARY/ABSTRACT: MICROBIOME CORE The Microbiome (MIBI) Core plays an essential role in the HNRC by enabling researchers to investigate the emerging, complex links between the gut microbiome, HIV, associated comorbidities, and biological mechanisms involved in neurocognitive impairment (NCI), mood disorders, and more complex neurobehavioral phenotypes that include both. In recent years, the gut microbiome has been strongly associated with neurologic and mood disorders in individual studies, although few studies have considered them together, and none in the context of HIV. In particular, questions about how HIV infection and ART may impact gut barrier dysfunction and central nervous system sequelae from a microbiome perspective have not been well studied. However, detailed mechanistic accounts of how the microbiome is involved in depression and Type 2 diabetes, and interacts with viral infection in a non-HIV context, strongly motivate such studies. The main goal of MIBI is therefore to make microbiome and metabolome technology broadly available to HNRC investigators, allowing us to go beyond the 16S rRNA profiling from the NeuroGerm (NG) core in the previous funding period, and focusing on microbiome- related mechanisms of mood and cognitive changes in people with HIV (PWH). To provide insight beyond taxonomic profiling, we will use advanced shotgun metagenomics techniques to read out and assemble bacterial and viral genomes from stool and plasma, and relate these to chemical profiles from untargeted metabolomics, which will also capture drugs and their downstream metabolites and allow us to connect these processes to the microbiome in PWH. Because the microbiome is known to be affected by host genetics, and is likely to interact with viral genotype and titer, close interaction with the other Cores will be essential for enabling researchers to make progress on these questions that require complex multidisciplinary study designs. Additionally, because analysis of highly multivariate microbiome and metabolome data is challenging, an important goal of MIBI will be to provide bioinformatics support and training in how to integrate these data layers with each other and with clinical data important to furthering these scientific aims. The result will be a better understanding of how the microbiome influences and is influenced by long-term HIV infection and co-infections, and how microbiome and metabolome changes may influence individual responses to treatments for HIV and associated conditions (including depressive states and NCI), and ultimately contribute to improved strategies for long-term management of HIV that take the microbiome into account to reduce long-term comorbidities.