Microbiome Core

项目摘要/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，使研究人员能够研究 肠道微生物群、艾滋病毒、相关的共病和生物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 这两个都包括在内。近年来，肠道微生物群与神经学和情绪密切相关。 个别研究中的障碍，尽管很少有研究将它们放在一起考虑，也没有一项研究是在 爱滋病毒。特别是，关于艾滋病毒感染和抗逆转录病毒治疗可能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，神经系统后遗症还没有得到很好的研究。然而，详细的 微生物组如何参与抑郁症和2型糖尿病，并与 病毒感染在非艾滋病毒的背景下，强烈地推动了这类研究。因此，MIBI的主要目标是使 微生物组和代谢组技术广泛可供HNRC研究人员使用，使我们能够超越 上一次资助期间的NeuroGerm(NG)核心的16S rRNA图谱，并专注于微生物组- HIV感染者情绪和认知改变的相关机制。提供超越现实的洞察力 分类图谱，我们将使用先进的鸟枪式元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，并将这些与非靶向代谢组学的化学特征相关联， 它还将捕获药物及其下游代谢物，并允许我们将这些过程与 威斯康星医院的微生物群。因为微生物群已知受到宿主遗传的影响，并可能相互作用 有了病毒的基因型和滴度，与其他核心的密切互动将是使研究人员能够 在这些需要复杂的多学科研究设计的问题上取得进展。另外，因为 分析高度多变量的微生物组和代谢组数据是具有挑战性的，MIBI的一个重要目标将是 提供生物信息学支持和培训，了解如何将这些数据层相互集成，并与 临床数据对促进这些科学目标很重要。其结果将是更好地理解 微生物组影响和受长期HIV感染和混合感染的影响，以及微生物组和 代谢组的变化可能会影响个体对艾滋病毒及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 对艾滋病毒的管理，将微生物群考虑在内，以减少长期共病。

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.