The Salivary Microbiota, Cytokines, and Metabolome in Patients with Ankylosing Spondylitis Are Altered and More Proinflammatory than Those in Healthy Controls.

Abstract

ABSTRACTThe 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 α (sIL-6Rα), 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-α2), IFN-β, 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.