OBJECTIVE To investigate whether a probiotic supplementation to cART patients modifies the cerebrospinal fluid (CSF) proteome and improves neurocognitive impairment. METHODS 26 CSF samples from 13 HIV-positive patients [six patients living with HIV (PLHIV) and seven patients with a history of AIDS (PHAIDS)] were analyzed. All patients underwent to neurocognitive evaluation and blood sampling at baseline and after 6 months of oral bacteriotherapy. Immune phenotyping and activation markers (CD38 and HLA-DR) were evaluated on peripheral blood mononuclear cells (PBMC). Plasma levels of IL-6, sCD14, and MIP-1β were detected, by enzyme-linked immunosorbent assay (ELISA). Functional proteomic analysis of CSF sample was conducted by two-dimensional electrophoresis; a multivariate analysis was performed by principal component analysis (PCA) and data were enriched by STRING software. RESULTS Oral bacteriotherapy leads to an improvement on several cognitive test and neurocognitive performance in both groups of HIV-positive subjects. A reduction in the percentage of CD4+CD38+HLA-DR+ T cells was also observed at peripheral level after the probiotic intake (p = 0.008). In addition, the probiotic supplementation to cART significantly modifies protein species composition and abundance at the CSF level, especially those related to inflammation (β2-microglobulin p = 0.03; haptoglobin p = 0.06; albumin p = 0.003; hemoglobin p = 0.003; immunoglobulin heavy chains constant region p = 0.02, transthyretin p = 0.02) in PLHIV and PHAIDS. CONCLUSIONS Our results suggest that oral bacteriotherapy as a supplement to cART could exert a role in the amelioration of inflammation state at peripheral and CNS level.

中文翻译：

---

艾滋病毒患者口服细菌治疗后的认知障碍和脑脊液蛋白质组修饰。

目的探讨向cART患者补充益生菌是否会改变脑脊液（CSF）蛋白质组并改善神经认知障碍。方法分析了13例HIV阳性患者[6例HIV感染者（PLHIV）和7例AIDS史（PHAIDS）患者]的26例CSF样本。所有患者在基线和口服细菌治疗6个月后均接受神经认知评估和血液采样。在外周血单核细胞（PBMC）上评估了免疫表型和激活标记（CD38和HLA-DR）。通过酶联免疫吸附测定（ELISA）检测血浆IL-6，sCD14和MIP-1β的水平。通过二维电泳对脑脊液样本进行功能蛋白质组学分析。通过主成分分析（PCA）进行多变量分析，并通过STRING软件丰富数据。结果口服细菌疗法可改善两组HIV阳性受试者的几种认知测验和神经认知能力。摄入益生菌后，外周水平的CD4 + CD38 + HLA-DR + T细胞百分比也降低（p = 0.008）。此外，对cART的益生菌补充可以显着改变CSF水平的蛋白质种类组成和丰度，尤其是与炎症有关的蛋白质种类和丰度（β2-微球蛋白p = 0.03；触珠蛋白p = 0.06；白蛋白p = 0.003；血红蛋白p = 0.003；免疫球蛋白重PLHIV和PHAIDS中的链恒定区p = 0.02，运甲状腺素蛋白p = 0.02）。