PMID- 34156295 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210803 IS - 2379-5077 (Print) IS - 2379-5077 (Electronic) IS - 2379-5077 (Linking) VI - 6 IP - 3 DP - 2021 Jun 29 TI - The Salivary Microbiota, Cytokines, and Metabolome in Patients with Ankylosing Spondylitis Are Altered and More Proinflammatory than Those in Healthy Controls. PG - e0117320 LID - 10.1128/mSystems.01173-20 [doi] LID - e01173-20 AB - The pathogenesis of ankylosing spondylitis (AS) remains unclear but appears to be associated with heredity and the environment. The mouth links the external environment to the gut and lungs. In the present study, compared to that observed in healthy controls (HCs), AS saliva was depleted of Bacilli such as Streptococcus, enriched with Clostridia such as Veillonellaceae, and enriched with opportunistic pathogens from Proteobacteria such as Brucella spp. and Campylobacter concisus. AS saliva was enriched with 16 cytokines related to inflammation, such as soluble IL-6 receptor alpha (sIL-6Ralpha), interleukin 2 (IL-2), IL-10, IL-11, IL-12p40, IL-12p70, IL-20, IL-26, IL-27, IL-28A, IL-29, alpha 2 interferon (IFN-alpha2), IFN-beta, and matrix metalloproteinase 3 (MMP-3). AS saliva was also enriched with hazardous compounds, such as cadaverine and putrescine. AS-altered salivary bacteria, compounds, and cytokines are closely linked with disease indicators. Oral cleaning reduced the levels of proinflammatory cytokines and hazardous compounds in AS saliva compared with HC saliva. AS saliva induced the production of more proinflammatory cytokines, such as IL-12p70 and IL-8, by THP-1 monocyte-derived macrophages, than did HC saliva. The results highlight the importance of salivary microbes, cytokines, and compounds in the development and treatment of AS and provide new ideas for the pathogenesis and treatment of AS. IMPORTANCE Ankylosing spondylitis (AS) affects as much as 0.32% of the population in some districts and causes work disability in one-third of these patients. Microbes are considered to play important roles in AS pathogenesis, and the mouth links the environment to the lungs and the gut. Our results showed that opportunistic pathogens such as Brucella and Campylobacter are enriched in the saliva of AS patients with ankylosing spondylitis. In addition, proinflammatory cytokines and hazardous materials such as putrescine were also enriched in the saliva of AS patients.[AQ1 sentence edit] Interestingly, the opportunistic pathogens and hazardous materials detected in the saliva of AS patients were associated with disease indexes. The saliva of AS patients was shown to induce immune cells to secrete proinflammatory cytokines in vitro. Reducing the levels of salivary microbes can significantly reduce the hazardous materials present in the saliva of AS patients. Our results provide a new perspective on the potential role of salivary microbes, cytokines, and hazardous compounds in the pathogenesis and treatment of AS. FAU - Lv, Longxian AU - Lv L AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang Universitygrid.13402.34, Hangzhou, China. FAU - Jiang, Huiyong AU - Jiang H AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang Universitygrid.13402.34, Hangzhou, China. FAU - Yan, Ren AU - Yan R AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang Universitygrid.13402.34, Hangzhou, China. FAU - Xu, Danyi AU - Xu D AD - Department of Rheumatology, The First Affiliated Hospital, College of Medicine, Zhejiang Universitygrid.13402.34, Hangzhou, China. FAU - Wang, Kaicen AU - Wang K AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang Universitygrid.13402.34, Hangzhou, China. FAU - Wang, Qiangqiang AU - Wang Q AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang Universitygrid.13402.34, Hangzhou, China. FAU - Chen, Xiaoxiao AU - Chen X AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang Universitygrid.13402.34, Hangzhou, China. FAU - Li, Lanjuan AU - Li L AD - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang Universitygrid.13402.34, Hangzhou, China. LA - eng GR - 2018YFC2000500/MOST | National Key Research and Development Program of China/ GR - 81570512/National Natural Science Foundation of China (NSFC)/ GR - LQ19H030007/Natural Science Foundation of Zhejiang Province/ PT - Journal Article DEP - 20210622 PL - United States TA - mSystems JT - mSystems JID - 101680636 PMC - PMC8269253 OTO - NOTNLM OT - ankylosing spondylitis OT - cytokines OT - immunity OT - metabolome OT - salivary microbiota EDAT- 2021/06/23 06:00 MHDA- 2021/06/23 06:01 PMCR- 2021/06/22 CRDT- 2021/06/22 12:11 PHST- 2021/06/23 06:00 [pubmed] PHST- 2021/06/23 06:01 [medline] PHST- 2021/06/22 12:11 [entrez] PHST- 2021/06/22 00:00 [pmc-release] AID - mSystems01173-20 [pii] AID - 10.1128/mSystems.01173-20 [doi] PST - ppublish SO - mSystems. 2021 Jun 29;6(3):e0117320. doi: 10.1128/mSystems.01173-20. Epub 2021 Jun 22.