Presti Rachel M, Yeh Eunice, Williams Brett, Landay Alan, Jacobson Jeffrey M, Wilson Cara, Fichtenbaum Carl J, Utay Netanya S, Dube Michael P, Klingman Karin L, Estes Jacob D, Flynn Jacob K, Loftin Amanda, Brenchley Jason M, Andrade Adriana, Kitch Douglas W, Overton Edgar T
Washington University School of Medicine, St. Louis, Missouri, USA.
Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Open Forum Infect Dis. 2021 Dec 7;8(12):ofab550. doi: 10.1093/ofid/ofab550. eCollection 2021 Dec.
A5350, a phase II, randomized, double-blind study, evaluated the safety and tolerability of the probiotic Visbiome Extra Strength (ES) over 24 weeks and measured effects on inflammation and intestinal barrier function.
The primary outcome was change in soluble CD14 (sCD14) levels; secondary outcomes included safety and tolerability, markers of inflammation and cellular activation, and microbiome. In a substudy, gut permeability was assessed by paired colonic biopsies measuring the area of lamina propria occupied by CD4+ cells, interleukin (IL)-17+ cells, and myeloperoxidase (MPO). Changes between arms were compared with the 2-sample test with equal variance or the Wilcoxon rank-sum test. For safety, the highest graded adverse events (AEs) were compared between arms using the Fisher exact test.
Overall, 93 participants enrolled: 86% male, median age 51 years, median CD4 count 712 cells/mm3. Visbiome ES was safe and well tolerated. There was no difference in mean change in sCD14 from baseline to week 25/26 between placebo (mean change, 92.3 µg/L; 95% CI, -48.5 to 233 µg/L) and Visbiome ES (mean change, 41.0 µg/L; 95% CI, -94.1 to 176.2 µg/L; =.60). Similarly, no statistically significant differences between arms in inflammatory marker changes were identified. In substudy participants, no statistical differences between arms for change in cellular marker expression or gut permeability were observed (>.05 for all). The microbiome demonstrated increased probiotic species and a significant decrease in (=.044) in the Visbiome ES arm.
Visbiome ES was safe and altered the microbiome but demonstrated no effect on systemic inflammatory markers, pathology, or gut permeability in antiretroviral therapy-treated people with HIV.
A5350是一项II期随机双盲研究，评估了益生菌超强卫乐舒（Visbiome Extra Strength，ES）在24周内的安全性和耐受性，并测量了其对炎症和肠道屏障功能的影响。
主要结局是可溶性CD14（sCD14）水平的变化；次要结局包括安全性和耐受性、炎症和细胞活化标志物以及微生物组。在一项子研究中，通过配对结肠活检评估肠道通透性，测量固有层中CD4+细胞、白细胞介素（IL）-17+细胞和髓过氧化物酶（MPO）所占面积。两组之间的变化采用等方差双样本检验或Wilcoxon秩和检验进行比较。对于安全性，使用Fisher精确检验比较两组中分级最高的不良事件（AE）。
总体而言，93名参与者入组：86%为男性，中位年龄51岁，中位CD4细胞计数为712个/mm³。超强卫乐舒安全且耐受性良好。安慰剂组（平均变化，92.3μg/L；95%CI，-48.5至233μg/L）和超强卫乐舒组（平均变化，41.0μg/L；95%CI，-94.1至176.2μg/L；P = 0.60）从基线到第25/26周sCD14的平均变化无差异。同样，两组之间在炎症标志物变化方面未发现统计学上的显著差异。在子研究参与者中，两组在细胞标志物表达变化或肠道通透性方面未观察到统计学差异（所有P>0.05）。微生物组显示超强卫乐舒组的益生菌种类增加，且多样性显著降低（P = 0.044）。
超强卫乐舒安全且改变了微生物组，但在接受抗逆转录病毒治疗的HIV感染者中，对全身炎症标志物、病理学或肠道通透性无影响。
