The salivary microbiota, cytokines and metabolome in patients with ankylosing spondylitis are altered and more proinflammatory than those in healthy controls

Background: The role of microbes and their products in ankylosing spondylitis (AS) has been widely studied. We investigated alterations in the oral microbiota, immunity and metabolome in AS patients using saliva and explored the potential impact of these alterations on AS.Methods: Thirty-seven well-screened AS patients without any other diseases and 41 healthy controls (HCs) were enrolled. Their clinical characteristics, such as blood parameters and disease activity, were evaluated. Their salivary microbiota, 48 kinds of cytokines, and metabolomes were assayed using samples collected in the morning before toothbrushing. The ability of the salivary microbiota and supernatant to induce inflammation in OKF6 cells and THP-1-derived macrophages was studied. The cytokine and metabolome alterations after the oral microbiome was reduced by toothbrushing were studied.Results: Compared with that in 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 sp. and Campylobacter concisus. Furthermore, 16 salivary cytokines, such as IL-12P40 and IL-12P70, and 26 metabolites, such as 5-aminovaleric acid, cadaverine and putrescine, were significantly enriched in AS patients compared to HCs. After toothbrushing, the levels of a greater number of cytokines and metabolites were decreased in AS saliva compared to HC saliva. The microbes or supernatants of AS patient saliva induced the production of more cytokines, such as IL-12p70 and IL-8, by THP-1 macrophages than those of HC saliva.Conclusions: The salivary microbiota of AS patients is altered and more harmful to health than that of HCs.