Dysbiotic oral microbiota and infected salivary glands in Sjogren's syndrome
Dysbiotic oral microbiota and infected salivary glands in Sjogren's syndrome
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DOI：
10.1371/journal.pone.0230667
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发表时间：
2020-03-24
期刊：
影响因子：
3.7
通讯作者：
Choi, Youngnim
中科院分区：
文献类型：
--
作者：
Alam, Jehan;Lee, Ahreum;Choi, Youngnim
干燥综合征（SS）发病的关键事件包括唾液腺上皮细胞转变为抗原呈递细胞样表型和局灶性淋巴细胞性涎腺炎（FLS）。然而，在SS中触发这些特征的原因尚不清楚。肠道和口腔微生物群的生态失调是SS的潜在环境因素，但其与SS发病机制的关系尚不清楚。本研究旨在研究SS患者口腔微生物群特征，并探讨其在SS发病机制中的潜在作用。采用全漱口水收集对照组（14例无口腔干燥，11例有口腔干燥）和原发SS患者（8例无口腔干燥，17例有口腔干燥）的口腔细菌群落，并进行焦磷酸测序分析。SS口腔微生物群的特征是细菌负荷和Shannon多样性增加。通过对比对照和干燥对照，再分别在干燥和非干燥条件下鉴定出与干燥无关的SS相关分类群。选择3种ss相关种和2种对照种，用于攻击人颌下腺肿瘤（HSG）细胞。在选定的ss相关细菌种类中，黑色素生成普雷沃氏菌独特地上调HSG细胞中MHC分子、CD80和IFN lambda的表达。同时，黑素假单胞菌有效侵袭HSG细胞。8例非SS患者和15例SS患者的唇唾液腺（LSG）活检切片采用通用探针和黑色素增生假单胞菌特异性探针进行原位杂交。在FLS的LSGs中，导管细胞和浸润区域被细菌严重感染。总的来说，口腔菌群失调可能通过细菌侵入导管细胞而引发sges和IFN信号的失调。这些发现可能为SS的发病机制提供新的认识。
Key events in the pathogenesis of Sjogren syndrome (SS) include the change of salivary gland epithelial cells into antigen-presenting cell-like phenotypes and focal lymphocytic sialadenitis (FLS). However, what triggers these features in SS is unknown. Dysbiosis of the gut and oral microbiomes is a potential environmental factor in SS, but its connection to the etiopathogenesis of SS remains unclear. This study aimed to characterize the oral microbiota in SS and to investigate its potential role in the pathogenesis of SS. Oral bacterial communities were collected by whole mouthwash from control subjects (14 without oral dryness and 11 with dryness) and primary SS patients (8 without oral dryness and 17 with dryness) and were analyzed by pyrosequencing. The SS oral microbiota was characterized by an increased bacterial load and Shannon diversity. Through comparisons of control and SS in combined samples and then separately in non-dry and dry conditions, SS-associated taxa independent of dryness were identified. Three SS-associated species and 2 control species were selected and used to challenge human submandibular gland tumor (HSG) cells. Among the selected SS-associated bacterial species, Prevotella melaninogenica uniquely upregulated the expression of MHC molecules, CD80, and IFN lambda in HSG cells. Concomitantly, P. melaninogenica efficiently invaded HSG cells. Sections of labial salivary gland (LSG) biopsies from 8 non-SS subjects and 15 SS patients were subjected to in situ hybridization using universal and P. melaninogenica-specific probes. Ductal cells and the areas of infiltration were heavily infected with bacteria in the LSGs with FLS. Collectively, dysbiotic oral microbiota may initiate the deregulation of SGECs and the IFN signature through bacterial invasion into ductal cells. These findings may provide new insights into the etiopathogenesis of SS.