Role of Innate Oral Immunity and the Salivary Fluid in Inflammatory Bowel Disease.

Abstract

BACKGROUND & AIMS: Oral and gut health are tightly connected through their microbiome and immunity, including in disease states. The oral adaptive immunity contributes to the severity of inflammatory bowel disease (IBD). However, the role of oral innate immunity, and more specifically the saliva, in gut microbiome and IBD is poorly understood. METHODS: We used 2 mouse models with reduced saliva, nonobese diabetic (NOD) and aquaporin 5 (Aqp5)mice, and recovery of salivation in the NOD mice by treatment with a cystic fibrosis transmembrane regulator corrector to examine the role of salivation in oral and gut microbiome, IBD, and survival. RESULTS: Analysis of the oral microbiome at various conditions revealed that the saliva has a minimal role in shaping the oral microbiome. However, salivation affected the composition of the gut microbiome. Moreover, the lack of saliva significantly delayed development of dextran sodium sulphate-induced colitis, but resulted in a later, age-dependent, rapidly developed weight loss and death. The dual roles of the saliva were caused by 2 immunomodulatory peptides secreted by salivary glands. Fractionation and mass spectroscopy analysis identified trefoil factor 2 (TFF2) as a protective component and the cytokine macrophage migration inhibitory factor (MIF) as the damaging component of the saliva. The effects of the salivary fluid, TFF2, and MIF were primarily due to control of the gut barrier, rather than the gut microbiome. Scavenging salivary TFF2 and MIF with antibodies resulted in exacerbating and protection, respectively, of IBD. CONCLUSIONS: The oral innate immunity has a major role in shaping the gut microbiome through secretion of MIF and TFF2. Control of MIF and TFF2 can benefit the treatment of colitis.