Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.
Beijing Key Laboratory for HIV/AIDS Research, Beijing Youan Hospital, Capital Medical University, Beijing, China.
Ann Neurol. 2024 Aug;96(2):306-320. doi: 10.1002/ana.26963. Epub 2024 May 16.
Although accumulating evidence implicating altered gut microbiota in human immunodeficiency virus (HIV) infection and neurodegenerative disorders; however, the association between dysbiosis of the gut microbiota and metabolites in the pathogenesis of HIV-associated neurocognitive disorder (HAND) remains unclear.
Fecal and plasma samples were obtained from 3 cohorts (HAND, HIV-non-HAND, and healthy controls), metagenomic analysis and metabolomic profiling were performed to investigate alterations in the gut microbial composition and circulating metabolites in HAND.
The gut microbiota of people living with HIV (PLWH) had an increased relative abundance of Prevotella and a decreased relative abundance of Bacteroides. In contrast, Prevotella and Megamonas were substantially decreased, and Bacteroides and Phocaeicola were increased in HAND patients. Moreover, untargeted metabolomics identified several neurotransmitters and certain amino acids associated with neuromodulation, and the differential metabolic pathways of amino acids associated with neurocognition were depleted in HAND patients. Notably, most neuromodulatory metabolites are associated with an altered abundance of specific gut bacteria.
Our findings provide new insights into the intricate interplay between the gut and microbiome-brain axis in the pathogenesis of HAND, highlighting the potential for developing novel therapeutic strategies that specifically target the gut microbiota. ANN NEUROL 2024;96:306-320.
尽管越来越多的证据表明肠道微生物群的改变与人类免疫缺陷病毒（HIV）感染和神经退行性疾病有关；然而，肠道微生物群失调与 HIV 相关认知障碍（HAND）发病机制中的代谢物之间的关联仍不清楚。
从 3 个队列（HAND、HIV 非 HAND 和健康对照）中获得粪便和血浆样本，进行宏基因组分析和代谢组学分析，以研究 HAND 中肠道微生物组成和循环代谢物的变化。
HIV 感染者（PLWH）的肠道微生物群中普雷沃氏菌的相对丰度增加，而拟杆菌的相对丰度降低。相反，HAND 患者中普雷沃氏菌和 Megamonas 显著减少，而拟杆菌和 Phocaeicola 增加。此外，非靶向代谢组学鉴定出与神经调节相关的几种神经递质和某些氨基酸，与神经认知相关的氨基酸的差异代谢途径在 HAND 患者中被耗尽。值得注意的是，大多数神经调节代谢物与特定肠道细菌的丰度改变有关。
我们的研究结果提供了肠道与微生物群-大脑轴在 HAND 发病机制中的复杂相互作用的新见解，强调了开发专门针对肠道微生物群的新型治疗策略的潜力。ANN NEUROL 2024；96:306-320。
