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.