Tian Xuebin, Gao Zhongyao, Xie Yiwen, Lu Xiangyun, Zhao Yulong, Yao Peng, Dong Mingqing, Yu Lifeng, Wu Nanping
Cell Biology Research Platform, Jinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong, China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Curr Res Microb Sci. 2025 Jan 10;8:100340. doi: 10.1016/j.crmicr.2025.100340. eCollection 2025.
Antiretroviral therapy (ART) effectively reduces opportunistic infections and mortality in people living with HIV (PLWH); however, some patients exhibit poor immune recovery. This study explores the connections among immune responses, metabolites, and the gut microbiota in PLWH with differing reactions to ART.
We analyzed the gut microbiota composition, metabolites, and immune markers in 38 PLWH who showed an immunological response (IR) and 32 who did not (INR), as classified according to CD4+ T-cell levels after 24 months of ART. Additionally, in vitro assays using cell counting kit 8, flow cytometry, and quantitative real-time reverse transcription PCR were employed to assess the effects of the metabolites on cell viability, immune marker expression, and cytokine levels.
Gut microbiota and metabolic profiles differed significantly between the IR and INR groups. was more abundant in the INR group, whereas levels were reduced. Significant metabolic pathway alterations included decreased folate biosynthesis and biotin metabolism. We observed negative associations of with activation markers on CD4+ T-cells, and positive correlations with CD4/CD8 ratios. showed inverse relationships with these markers. Indole-3-acetyl-beta-1-D-glucoside (area under the curve value = 0.8931), had the best discriminatory ability. Further experiments showed that Indole-3-acetyl-beta-1-D-glucoside significantly decreased the proportions of CD4+CD57+, effector CD4+, CD4+PD1+, CD8+CD57+, effector CD8+, and CD8+HLA-DR+ T cells. Moreover, mRNA expression analysis showed that Indole-3-acetyl-beta-1-D-glucoside treatment led to a suppression of pro-inflammatory cytokines.
The multi-omics approach highlighted potential biomarkers for immune recovery in HIV, suggesting avenues for further research into treatment strategies.
抗逆转录病毒疗法（ART）可有效降低HIV感染者（PLWH）的机会性感染和死亡率；然而，一些患者的免疫恢复情况较差。本研究探讨了对ART反应不同的PLWH的免疫反应、代谢物和肠道微生物群之间的联系。
我们分析了38名表现出免疫反应（IR）和32名未表现出免疫反应（INR）的PLWH 的肠道微生物群组成、代谢物和免疫标志物，这些是根据ART 24个月后的CD4+T细胞水平分类的。此外，使用细胞计数试剂盒8、流式细胞术和定量实时逆转录PCR进行体外试验，以评估代谢物对细胞活力、免疫标志物表达和细胞因子水平的影响。
IR组和INR组的肠道微生物群和代谢谱存在显著差异。 在INR组中更为丰富，而 水平降低。显著的代谢途径改变包括叶酸生物合成和生物素代谢减少。我们观察到 与CD4+T细胞上的激活标志物呈负相关，与CD4/CD8比值呈正相关。 与这些标志物呈反比关系。吲哚-3-乙酰-β-1-D-葡萄糖苷（曲线下面积值=0.8931）具有最佳的鉴别能力。进一步的实验表明，吲哚-3-乙酰-β-1-D-葡萄糖苷显著降低了CD4+CD57+、效应CD4+、CD4+PD1+、CD8+CD57+、效应CD8+和CD8+HLA-DR+T细胞的比例。此外，mRNA表达分析表明，吲哚-3-乙酰-β-1-D-葡萄糖苷处理导致促炎细胞因子的抑制。
多组学方法突出了HIV免疫恢复的潜在生物标志物，为治疗策略的进一步研究提供了途径。
