1] Unidad Mixta de Investigación en Genómica y Salud de la Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO-Salud Pública) y el Instituto Cavanilles de Biodiversitad y Biología Evolutiva (Universitat de València), Valencia, Spain [2] CIBER on Epidemiology and Public Health (CIBERESP), Madrid, Spain.
Department of Infectious Diseases, University Hospital Ramón y Cajal-IRYCIS, Madrid, Spain.
Mucosal Immunol. 2015 Jul;8(4):760-72. doi: 10.1038/mi.2014.107. Epub 2014 Nov 19.
Altered interplay between gut mucosa and microbiota during treated HIV infection may possibly contribute to increased bacterial translocation and chronic immune activation, both of which are predictors of morbidity and mortality. Although a dysbiotic gut microbiota has recently been reported in HIV+ individuals, the metagenome gene pool associated with HIV infection remains unknown. The aim of this study is to characterize the functional gene content of gut microbiota in HIV+ patients and to define the metabolic pathways of this bacterial community, which is potentially associated with immune dysfunction. We determined systemic markers of innate and adaptive immunity in a cohort of HIV-infected individuals on successful antiretroviral therapy without comorbidities and in healthy non-HIV-infected subjects. Metagenome sequencing revealed an altered functional profile, with enrichment of the genes involved in various pathogenic processes, lipopolysaccharide biosynthesis, bacterial translocation, and other inflammatory pathways. In contrast, we observed depletion of genes involved in amino acid metabolism and energy processes. Bayesian networks showed significant interactions between the bacterial community, their altered metabolic pathways, and systemic markers of immune dysfunction. This study reveals altered metabolic activity of microbiota and provides novel insight into the potential host-microbiota interactions driving the sustained inflammatory state in successfully treated HIV-infected patients.
在接受治疗的 HIV 感染期间，肠道黏膜和微生物群之间相互作用的改变可能导致细菌易位和慢性免疫激活增加，这两者都是发病率和死亡率的预测因素。尽管最近有研究报道 HIV+个体的肠道微生物群失调，但与 HIV 感染相关的宏基因组基因库仍然未知。本研究旨在描述 HIV+患者肠道微生物群的功能基因含量，并定义与免疫功能障碍相关的细菌群落的代谢途径。我们在成功接受抗逆转录病毒治疗且无合并症的 HIV 感染个体和健康的非 HIV 感染个体中确定了先天和适应性免疫的系统标志物。宏基因组测序揭示了功能谱的改变，与各种致病过程、脂多糖生物合成、细菌易位和其他炎症途径相关的基因富集。相比之下，我们观察到参与氨基酸代谢和能量过程的基因减少。贝叶斯网络显示细菌群落、其改变的代谢途径与免疫功能障碍的系统标志物之间存在显著的相互作用。这项研究揭示了微生物群的代谢活性改变，并为成功治疗的 HIV 感染患者中持续炎症状态的潜在宿主-微生物群相互作用提供了新的见解。
