Department of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
BMC Complement Altern Med. 2012 Jun 29;12:84. doi: 10.1186/1472-6882-12-84.
Infection with HIV-1 results in marked immunologic insults and structural damage to the intestinal mucosa, including compromised barrier function. While the development of highly active antiretroviral therapy (HAART) has been a major advancement in the treatment of HIV-1 infection, the need for novel complementary interventions to help restore intestinal structural and functional integrity remains unmet. Known properties of pre-, pro-, and synbiotics suggest that they may be useful tools in achieving this goal.
This was a 4-week parallel, placebo-controlled, randomized pilot trial in HIV-infected women on antiretroviral therapy. A synbiotic formulation (Synbiotic 2000®) containing 4 strains of probiotic bacteria (10(10) each) plus 4 nondigestible, fermentable dietary fibers (2.5 g each) was provided each day, versus a fiber-only placebo formulation. The primary outcome was bacterial translocation. Secondary outcomes included the levels of supplemented bacteria in stool, the activation phenotype of peripheral T-cells and monocytes, and plasma levels of C-reactive protein and soluble CD14.
Microbial translocation, as measured by plasma bacterial 16S ribosomal DNA concentration, was not altered by synbiotic treatment. In contrast, the synbiotic formulation resulted in significantly elevated levels of supplemented probiotic bacterial strains in stool, including L. plantarum and P. pentosaceus, with the colonization of these two species being positively correlated with each other. T-cell activation phenotype of peripheral blood lymphocytes showed modest changes in response to synbiotic exposure, with HLA-DR expression slightly elevated on a minor population of CD4+ T-cells which lack expression of HLA-DR or PD-1. In addition, CD38 expression on CD8+ T-cells was slightly lower in the fiber-only group. Plasma levels of soluble CD14 and C-reactive protein were unaffected by synbiotic treatment in this study.
Synbiotic treatment for 4 weeks can successfully augment the levels of probiotic species in the gut during chronic HIV-1 infection. Associated changes in microbial translocation appear to be absent, and markers of systemic immune activation appear largely unchanged. These findings may help inform future studies aimed at testing pre- and probiotic approaches to improve gut function and mucosal immunity in chronic HIV-1 infection.
Clinical Trials.gov: NCT00688311.
HIV-1 感染会导致肠道黏膜明显的免疫损伤和结构损伤，包括屏障功能受损。虽然高效抗逆转录病毒疗法 (HAART) 的发展是 HIV-1 感染治疗的重大进展，但仍需要新的补充干预措施来帮助恢复肠道结构和功能的完整性。前、益生菌和合生剂的已知特性表明，它们可能是实现这一目标的有用工具。
这是一项为期 4 周的平行、安慰剂对照、随机试验，纳入了接受抗逆转录病毒治疗的 HIV 感染女性。每天给予一种合生剂配方（Synbiotic 2000®），其中含有 4 种益生菌菌株（各 10（10））和 4 种不可消化的可发酵膳食纤维（各 2.5 g），与纤维仅安慰剂配方进行比较。主要结局是细菌易位。次要结局包括粪便中补充细菌的水平、外周 T 细胞和单核细胞的激活表型以及血浆 C 反应蛋白和可溶性 CD14 的水平。
通过血浆细菌 16S 核糖体 DNA 浓度测量的微生物易位，并没有因合生剂治疗而改变。相比之下，合生剂配方可显著提高粪便中补充益生菌菌株的水平，包括植物乳杆菌和戊糖片球菌，这两种菌的定植与彼此呈正相关。外周血淋巴细胞 T 细胞激活表型在合生剂暴露后略有变化，少数缺乏 HLA-DR 或 PD-1 表达的 CD4+T 细胞上 HLA-DR 表达略有升高。此外，纤维仅组 CD8+T 细胞上 CD38 的表达略低。本研究中，合生剂治疗对可溶性 CD14 和 C 反应蛋白的血浆水平没有影响。
在慢性 HIV-1 感染期间，合生剂治疗 4 周可成功增加肠道内益生菌的水平。与微生物易位相关的变化似乎不存在，全身免疫激活的标志物基本不变。这些发现可能有助于为未来旨在改善慢性 HIV-1 感染中肠道功能和黏膜免疫的益生菌和预生物方法的研究提供信息。
ClinicalTrials.gov：NCT00688311。
