IrsiCaixa, Badalona, Catalonia, Spain.
Universitat de Barcelona, Barcelona, Catalonia, Spain.
Retrovirology. 2024 Nov 29;21(1):21. doi: 10.1186/s12977-024-00655-w.
The rapid establishment and persistence of latent HIV-1 reservoirs is one of the main obstacles towards an HIV cure. While antiretroviral therapy supresses viral replication, it does not eradicate the latent reservoir of HIV-1-infected cells. Recent evidence suggests that the human microbiome, particularly the gut microbiome, may have the potential to modulate the HIV-1 reservoir. However, literature is limited and the exact mechanisms underlying the role of the microbiome in HIV immunity and potential regulation of the viral reservoir remain poorly understood.
Here, we review updated knowledge on the associations between the human microbiome and HIV reservoir across different anatomical sites, including the gut, the lungs and blood. We provide an overview of the predominant taxa associated with prominent microbiome changes in the context of HIV infection. Based on the current evidence, we summarize the main study findings, with specific focus on consistent bacterial and related byproduct associations. Specifically, we address the contribution of immune activation and inflammatory signatures on HIV-1 persistence. Furthermore, we discuss possible scenarios by which bacterial-associated inflammatory mediators, related metabolites and host immune signatures may modulate the HIV reservoir size. Finally, we speculate on potential implications of microbiome-based therapeutics for future HIV-1 cure strategies, highlighting challenges and limitations inherent in this research field.
Despite recent advances, this review underscores the need for further research to deepen the understanding of the complex interplay between the human microbiome and HIV reservoir. Further integrative multi-omics assessments and functional studies are crucial to test the outlined hypothesis and to identify potential therapeutic targets ultimately able to achieve an effective cure for HIV.
潜伏的 HIV-1 储库的快速建立和持续存在是 HIV 治愈的主要障碍之一。虽然抗逆转录病毒疗法抑制了病毒复制，但它并不能根除 HIV-1 感染细胞的潜伏储库。最近的证据表明，人类微生物组，特别是肠道微生物组，可能具有调节 HIV-1 储库的潜力。然而，文献有限，微生物组在 HIV 免疫和潜在调节病毒储库中的作用的确切机制仍知之甚少。
在这里，我们综述了不同解剖部位（包括肠道、肺部和血液）中人类微生物组与 HIV 储库之间关联的最新知识。我们概述了与 HIV 感染相关的主要微生物组变化相关的主要分类群。根据目前的证据，我们总结了主要的研究结果，特别关注一致的细菌和相关副产物关联。具体而言，我们解决了免疫激活和炎症特征对 HIV-1 持续存在的贡献。此外，我们讨论了细菌相关炎症介质、相关代谢物和宿主免疫特征可能调节 HIV 储库大小的可能情况。最后，我们推测基于微生物组的治疗方法对未来 HIV-1 治愈策略的潜在影响，强调了该研究领域固有的挑战和局限性。
尽管最近取得了进展，但本综述强调需要进一步研究，以加深对人类微生物组与 HIV 储库之间复杂相互作用的理解。进一步的综合多组学评估和功能研究对于测试所提出的假设和确定潜在的治疗靶点至关重要，这些靶点最终能够实现 HIV 的有效治愈。
