Association of a dysbiotic oral microbiota with the development of focal lymphocytic sialadenitis in IκB-ζ-deficient mice

Mice lacking IκB-ζ, a protein encoded by the Nfkbiz gene, spontaneously develop a Sjögren’s syndrome-like disease involving the lachrymal glands, but no salivary gland symptoms have been reported. We found that Nfkbiz(−/−) female mice presented a significantly reduced salivary flow rate, focal lymphocytic sialadenitis (FLS), and a dysbiotic oral microbiota at week 24. To dissect the contributions of genetic and environmental factors to the salivary gland phenotype, Nfkbiz(+/+) and Nfkbiz(−/−) mice were cohoused after weaning and evaluated at week 20. Cohousing alleviated the salivary gland phenotype of Nfkbiz(−/−) mice but did not induce any disease phenotype in Nfkbiz(+/+) mice. Additionally, the oral microbiota in the cohoused mice was synchronized toward that in Nfkbiz(+/+) mice. In conclusion, IκB-ζ-deficient mice developed hyposalivation and FLS, in which a dysbiotic oral microbiota played an important role. This finding suggests that the dysbiotic oral microbiota could be a therapeutic target.