接受稳定抗逆转录病毒治疗的HIV感染者在益生菌干预后D-二聚体水平降低及肠道微生物群组成变化
Reduced Levels of D-dimer and Changes in Gut Microbiota Composition After Probiotic Intervention in HIV-Infected Individuals on Stable ART.
作者信息
Stiksrud Birgitte, Nowak Piotr, Nwosu Felix C, Kvale Dag, Thalme Anders, Sonnerborg Anders, Ueland Per M, Holm Kristian, Birkeland Stein-Erik, Dahm Anders E A, Sandset Per M, Rudi Knut, Hov Johannes R, Dyrhol-Riise Anne M, Trøseid Marius
机构信息
*Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway; †Department of Infectious Diseases, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; ‡Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; §Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences; ‖K.G. Jebsen Center for Inflammation Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; ¶Department of Clinical Science, University of Bergen, Bergen, Norway; #Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway; **Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway; ††TINE SA, TINE R&D, Oslo, Norway; ‡‡Department of Haematology, Akershus University Hospital, Nordbyhagen, Norway; §§Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Oslo, Norway; ‖‖Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway; and ¶¶Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Oslo, Norway.
出版信息
J Acquir Immune Defic Syndr. 2015 Dec 1;70(4):329-37. doi: 10.1097/QAI.0000000000000784.
BACKGROUND
Microbial translocation and chronic inflammation may contribute to non-AIDS morbidity in patients with HIV. This study assessed the impact of probiotic intervention on microbial translocation and inflammation in patients on antiretroviral therapy with viral suppression and subnormal CD4 count.
METHODS
Thirty-two patients receiving antiretroviral therapy (CD4 <500 cells/μL) were randomized in a double-blind fashion to multistrain daily probiotics (n = 15), placebo (n = 9), or controls (n = 8) for 8 weeks. Soluble inflammation markers, D-dimer, lipopolysaccharide (LPS), sCD14, T-cell activation, tryptophan metabolites, and gut microbiota composition were analyzed at baseline and end of study. Nonparametric statistics were applied.
RESULTS
Twenty-four participants completed the study and were included in as-treated analyses. In patients receiving probiotics, there was a significant reduction in D-dimer levels (median change 33%, P = 0.03) and a tendency to reduced levels of C-reactive protein (CRP) (P = 0.05) and interleukin (IL)-6 (P = 0.06). The changes in CRP and IL-6 were highly correlated (r = 0.95, P < 0.01), whereas changes in D-dimer did not correlate with changes in CRP or IL-6. Increases in Bifidobacteria (P = 0.04) and Lactobacilli (P = 0.06) were observed in the probiotic group, whereas the relative abundance of Bacteroides decreased (P ≤ 0.01). No significant changes were seen in markers of microbial translocation or T-cell activation. However, the expansion of Bifidobacteria correlated negatively with differences in LPS (r = -0.77, P = 0.01), whereas the reduction in Bacteroides correlated positively with changes in LPS during the study period (r = 0.72, P = 0.02).
CONCLUSIONS
Probiotic intervention seemed to reduce markers of coagulation and inflammation without overt changes in microbial translocation. These findings warrant further studies in larger cohorts with long-term follow-up.
背景
微生物易位和慢性炎症可能导致HIV患者出现非艾滋病相关发病情况。本研究评估了益生菌干预对接受抗逆转录病毒治疗且病毒得到抑制但CD4计数低于正常水平的患者的微生物易位和炎症的影响。
方法
32例接受抗逆转录病毒治疗（CD4<500个细胞/μL）的患者以双盲方式随机分为每日服用多菌株益生菌组（n = 15）、安慰剂组（n = 9）或对照组（n = 8），为期8周。在基线和研究结束时分析可溶性炎症标志物、D-二聚体、脂多糖（LPS）、可溶性CD14、T细胞活化、色氨酸代谢产物和肠道微生物群组成。应用非参数统计方法。
结果
24名参与者完成了研究并纳入治疗后分析。接受益生菌治疗的患者中，D-二聚体水平显著降低（中位数变化33%，P = 0.03），C反应蛋白（CRP）水平有降低趋势（P = 0.05），白细胞介素（IL）-6水平有降低趋势（P = 0.06）。CRP和IL-6的变化高度相关（r = 0.95，P < 0.01），而D-二聚体的变化与CRP或IL-6的变化无关。益生菌组中双歧杆菌（P = 0.04）和乳酸杆菌（P = 0.06）增加，而拟杆菌的相对丰度降低（P≤0.01）。微生物易位标志物或T细胞活化未见显著变化。然而，双歧杆菌的增加与LPS差异呈负相关（r = -0.77，P = 0.01），而拟杆菌的减少与研究期间LPS的变化呈正相关（r = 0.72，P = 0.02）。
结论
益生菌干预似乎可降低凝血和炎症标志物水平，而微生物易位无明显变化。这些发现值得在更大队列中进行长期随访的进一步研究。
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