Cervicovaginal microbiome dysbiosis is associated with proteome changes related to alterations of the cervicovaginal mucosal barrier
Cervicovaginal microbiome dysbiosis is associated with proteome changes related to alterations of the cervicovaginal mucosal barrier
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DOI：
10.1038/mi.2015.86
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发表时间：
2016-05-01
影响因子：
8
通讯作者：
van de Wijgert, J. H. H. M.
中科院分区：
文献类型：
--
作者：
Borgdorff, H.;Gautam, R.;van de Wijgert, J. H. H. M.
阴道微生物组（VMB）生态失调与HIV感染增加有关。宫颈阴道炎症和其他粘膜屏障的变化被认为具有重要作用，但人类数据很少。我们比较了50名卢旺达女性性工作者的人宫颈阴道蛋白质组的质谱分析，这些女性性工作者先前使用16 S系统发育微阵列聚类为4个VMB组;按照细菌多样性增加的顺序：卷曲乳杆菌为主的VMB（组1），惰性乳杆菌为主的VMB（组2），中度生态失调（组3）和重度生态失调（组4）。我们使用靶向（预定义的粘膜屏障蛋白的丰度）和非靶向（在所有鉴定的人类蛋白质中差异丰富的蛋白质）方法比较了这些VMB组之间的相对蛋白质丰度。随着细菌多样性的增加，我们发现：（粘蛋白5 B和5AC增加），细胞骨架改变（增加肌动蛋白组织蛋白;减少角蛋白和皮质包膜蛋白），增加作为细胞死亡标志的乳酸脱氢酶A/B，增加蛋白水解活性（增加蛋白酶体核心复合物蛋白/蛋白酶;减少抗蛋白酶）、改变的抗微生物肽平衡（增加银屑病蛋白、钙卫蛋白和组蛋白;减少溶菌酶和泛素）、增加促炎细胞因子和减少免疫球蛋白免疫球蛋白G1/2。虽然时间关系不能得出，我们的研究结果支持这一假设，即生态失调导致宫颈阴道炎症和其他有害的变化，粘膜屏障。
Vaginal microbiome (VMB) dysbiosis is associated with increased acquisition of HIV. Cervicovaginal inflammation and other changes to the mucosal barrier are thought to have important roles but human data are scarce. We compared the human cervicovaginal proteome by mass spectrometry of 50 Rwandan female sex workers who had previously been clustered into four VMB groups using a 16S phylogenetic microarray; in order of increasing bacterial diversity: Lactobacillus crispatus-dominated VMB (group 1), Lactobacillus iners-dominated VMB (group 2), moderate dysbiosis (group 3), and severe dysbiosis (group 4). We compared relative protein abundances among these VMB groups using targeted (abundance of pre-defined mucosal barrier proteins) and untargeted (differentially abundant proteins among all human proteins identified) approaches. With increasing bacterial diversity, we found: mucus alterations (increasing mucin 5B and 5AC), cytoskeleton alterations (increasing actin-organizing proteins; decreasing keratins and cornified envelope proteins), increasing lactate dehydrogenase A/B as markers of cell death, increasing proteolytic activity (increasing proteasome core complex proteins/proteases; decreasing antiproteases), altered antimicrobial peptide balance (increasing psoriasin, calprotectin, and histones; decreasing lysozyme and ubiquitin), increasing proinflammatory cytokines, and decreasing immunoglobulins immunoglobulin G1/2. Although temporal relationships cannot be derived, our findings support the hypothesis that dysbiosis causes cervicovaginal inflammation and other detrimental changes to the mucosal barrier.