Lv Longxian, Jiang Huiyong, Chen Xiaoxiao, Wang Qiangqiang, Wang Kaicen, Ye Jianzhong, Li Yating, Fang Daiqiong, Lu Yingfeng, Yang Liya, Gu Silan, Chen Jianing, Diao Hongyan, Yan Ren, Li Lanjuan
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Front Immunol. 2021 Jul 21;12:713647. doi: 10.3389/fimmu.2021.713647. eCollection 2021.
The role of host-microbiota interactions in primary biliary cholangitis (PBC) has received increased attention. However, the impact of PBC on the oral microbiota and contribution of the oral microbiota to PBC are unclear. In this study, thirty-nine PBC patients without other diseases and 37 healthy controls (HCs) were enrolled and tested for liver functions and haematological variables. Saliva specimens were collected before and after brushing, microbiota was determined using 16S rDNA sequencing, metabolomics was profiled using Gas Chromatography-Mass Spectrometer (GC-MS), 80 cytokines were assayed using biochips, and inflammation inducibility was evaluated using OKF6 keratinocytes and THP-1 macrophages. Finally, the effect of ultrasonic scaling on PBC was estimated. Compared with HCs, PBC saliva had enriched taxa such as Bacteroidetes, , and and depleted taxa such as , and . PBC saliva also had enriched sCD163, enriched metabolites such as 2-aminomalonic acid and 1-dodecanol, and depleted metabolites such as dodecanoic acid and propylene glycol. sCD163, 4-hydroxybenzeneacetic acid and 2-aminomalonic acid were significantly correlated with salivary cytokines, bacteria and metabolites. Salivary members, 2-aminomalonic acid, and sCD163 were positively correlated with liver function indicators such as serum alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). PBC salivary microbes induced more soluble interleukin (IL)-6 receptor α (sIL-6Rα), sIL-6Rβ and tumour necrosis factor ligand superfamily (TNFSF)13B from OKF6 keratinocytes, and PBC salivary supernatant induced more IL-6, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), chemokine (C-C motif) ligand (CCL)13, C-X-C motif chemokine (CXC)L1 and CXCL16 from THP-1 macrophages. Toothbrushing significantly reduced the expression of inflammatory cytokines such as IL-1β, IL-8 and TNF-α and harmful metabolites such as cadaverine and putrescine in PBC but not HC saliva after -value correction. The levels of ALP and bilirubin in PBC serum were decreased after ultrasonic scaling. Together, PBC patients show significant alterations in their salivary microbiota, likely representing one cause and treatment target of oral inflammation and worsening liver functions.
宿主-微生物群相互作用在原发性胆汁性胆管炎（PBC）中的作用已受到越来越多的关注。然而，PBC对口腔微生物群的影响以及口腔微生物群对PBC的作用尚不清楚。在本研究中，纳入了39例无其他疾病的PBC患者和37名健康对照（HC），并对其进行肝功能和血液学指标检测。在刷牙前后收集唾液标本，使用16S rDNA测序确定微生物群，使用气相色谱-质谱仪（GC-MS）分析代谢组学，使用生物芯片检测80种细胞因子，并使用OKF6角质形成细胞和THP-1巨噬细胞评估炎症诱导能力。最后，评估了超声洁治对PBC的影响。与HC相比，PBC唾液中拟杆菌门等分类群富集，而放线菌门、厚壁菌门和梭杆菌门等分类群减少。PBC唾液中sCD163也富集，2-氨基丙二酸和1-十二烷醇等代谢产物富集，而十二烷酸和丙二醇等代谢产物减少。sCD163、4-羟基苯乙酸和2-氨基丙二酸与唾液细胞因子、细菌和代谢产物显著相关。唾液中的韦荣球菌属成员、2-氨基丙二酸和sCD163与血清碱性磷酸酶（ALP）、天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）等肝功能指标呈正相关。PBC唾液微生物从OKF6角质形成细胞诱导出更多的可溶性白细胞介素（IL）-6受体α（sIL-6Rα）、sIL-6Rβ和肿瘤坏死因子配体超家族（TNFSF）13B，PBC唾液上清液从THP-1巨噬细胞诱导出更多的IL-6、IL-10、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、趋化因子（C-C基序）配体（CCL）13、C-X-C基序趋化因子（CXC）L1和CXCL16。刷牙后经校正P值，PBC唾液中白细胞介素-1β、白细胞介素-8和肿瘤坏死因子-α等炎性细胞因子以及尸胺和腐胺等有害代谢产物的表达显著降低，但HC唾液中未降低。超声洁治后PBC血清中ALP和胆红素水平降低。总之，PBC患者唾液微生物群存在显著改变，这可能是口腔炎症和肝功能恶化的一个原因及治疗靶点。
