Department of Clinical and Experimental Medicine, University of Florence, Florence 50134, Italy.
Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa 16126, Italy.
World J Gastroenterol. 2022 Feb 14;28(6):635-652. doi: 10.3748/wjg.v28.i6.635.
Human immunodeficiency virus type 1 (HIV-1) infection is characterized by persistent systemic inflammation and immune activation, even in patients receiving effective antiretroviral therapy (ART). Converging data from many cross-sectional studies suggest that gut microbiota (GM) changes can occur throughout including human immunodeficiency virus (HIV) infection, treated by ART; however, the results are contrasting. For the first time, we compared the fecal microbial composition, serum and fecal microbial metabolites, and serum cytokine profile of treatmentnaïve patients before starting ART and after reaching virological suppression, after 24 wk of ART therapy. In addition, we compared the microbiota composition, microbial metabolites, and cytokine profile of patients with CD4/CD8 ratio < 1 (immunological non-responders [INRs]) and CD4/CD8 > 1 (immunological responders [IRs]), after 24 wk of ART therapy.
To compare for the first time the fecal microbial composition, serum and fecal microbial metabolites, and serum cytokine profile of treatmentnaïve patients before starting ART and after reaching virological suppression (HIV RNA < 50 copies/mL) after 24 wk of ART.
We enrolled 12 treatmentnaïve HIV-infected patients receiving ART (mainly based on integrase inhibitors). Fecal microbiota composition was assessed through next generation sequencing. In addition, a comprehensive analysis of a blood broad-spectrum cytokine panel was performed through a multiplex approach. At the same time, serum free fatty acid (FFA) and fecal short chain fatty acid levels were obtained through gas chromatography-mass spectrometry.
We first compared microbiota signatures, FFA levels, and cytokine profile before starting ART and after reaching virological suppression. Modest alterations were observed in microbiota composition, in particular in the viral suppression condition, we detected an increase of and and a decrease of . Moreover, in the same condition, we also observed augmented levels of serum propionic and butyric acids. Contemporarily, a reduction of serum IP-10 and an increase of IL-8 levels were detected in the viral suppression condition. In addition, the same components were compared between IRs and INRs. Concerning the microflora population, we detected a reduction of and an increase of in INRs. Simultaneously, fecal isobutyric, isovaleric, and 2-methylbutyric acids were also increased in INRs.
Our results provided an additional perspective about the impact of HIV infection, ART, and immune recovery on the "microbiome-immunity axis" at the metabolism level. These factors can act as indicators of the active processes occurring in the gastrointestinal tract. Individuals with HIV-1 infection, before ART and after reaching virological suppression with 24 wk of ART, displayed a microbiota with unchanged overall bacterial diversity; moreover, their systemic inflammatory status seems not to be completely restored. In addition, we confirmed the role of the GM metabolites in immune reconstitution.
人类免疫缺陷病毒 1 型（HIV-1）感染的特征是持续的全身炎症和免疫激活，即使在接受有效抗逆转录病毒治疗（ART）的患者中也是如此。许多横断面研究的综合数据表明，肠道微生物群（GM）的变化可能发生在包括人类免疫缺陷病毒（HIV）感染在内的整个过程中，并且可以通过 ART 治疗；然而，结果却截然相反。我们首次比较了治疗前未接受治疗的患者在开始 ART 前和在接受 24 周 ART 治疗后达到病毒学抑制（HIV RNA<50 拷贝/ml）后的粪便微生物组成、血清和粪便微生物代谢产物以及血清细胞因子谱。此外，我们还比较了 24 周 ART 治疗后 CD4/CD8 比值<1（免疫无应答者[INRs]）和 CD4/CD8>1（免疫应答者[IRs]）患者的微生物群组成、微生物代谢产物和细胞因子谱。
首次比较治疗前未接受治疗的 HIV 感染患者在开始 ART 前和在接受 24 周 ART 治疗后达到病毒学抑制（HIV RNA<50 拷贝/ml）后的粪便微生物组成、血清和粪便微生物代谢产物以及血清细胞因子谱。
我们招募了 12 名接受 ART（主要基于整合酶抑制剂）治疗的治疗前未接受治疗的 HIV 感染患者。通过下一代测序评估粪便微生物群组成。此外，还通过多重方法对血液广谱细胞因子谱进行了全面分析。同时，通过气相色谱-质谱法获得血清游离脂肪酸（FFA）和粪便短链脂肪酸水平。
我们首先比较了在开始 ART 前和达到病毒学抑制后的微生物群特征、FFA 水平和细胞因子谱。在微生物群组成方面观察到了适度的改变，特别是在病毒抑制的情况下，我们检测到增加了 和 ，减少了 。此外，在同一条件下，我们还观察到血清丙酸和丁酸水平升高。同时，在病毒抑制的情况下，检测到血清 IP-10 水平降低，IL-8 水平升高。此外，还比较了 IRs 和 INRs 之间的相同成分。关于微生物群，我们在 INRs 中检测到 和 的减少， 和 的增加。同时，INRs 中的粪便异丁酸、异戊酸和 2-甲基丁酸也增加了。
我们的结果提供了一个额外的视角，了解 HIV 感染、ART 和免疫恢复对代谢水平上的“微生物组-免疫轴”的影响。这些因素可以作为胃肠道中发生的活跃过程的指标。在开始 ART 之前和接受 24 周 ART 治疗后达到病毒学抑制的 HIV-1 感染个体，其肠道微生物多样性总体上没有改变；此外，他们的全身炎症状态似乎没有完全恢复。此外，我们还证实了 GM 代谢物在免疫重建中的作用。
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