Association of a dysbiotic oral microbiota with the development of focal lymphocytic sialadenitis in I?B-?-deficient mice

Mice lacking I?B-?, a protein encoded by the Nfkbiz gene, spontaneously develop a Sjögren's syndrome-like disease involving the lacrimal 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, I?B-?-deficient mice developed hyposalivation and FLS, in which a dysbiotic oral microbiota played a critical role. This finding suggests that the dysbiotic oral microbiota could be a novel therapeutic target.