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.

缺乏由Nfkbiz基因编码的蛋白质IκB-ζ的小鼠自发地发展为涉及泪腺的Sjögren综合征样疾病，但没有唾液腺症状的报道。我们发现Nfkbiz ^-/-雌性小鼠在第24周表现出唾液流速显着降低，局灶性淋巴细胞性涎腺炎（FLS）以及口腔中的益生菌。要解剖遗传和环境因素对唾液腺表型的贡献，Nfkbiz ⁺断奶后将^{/ +}和Nfkbiz ^-/-小鼠放养，并在第20周进行评估。饲养减轻了Nfkbiz ^-/-小鼠的唾液腺表型，但未诱导任何疾病表型。Nfkbiz ^{+ / +}小鼠。另外，将共同饲养的小鼠中的口腔微生物群与Nfkbiz ^{+ / +}小鼠的口腔微生物群同步。总之，IκB-ζ缺陷型小鼠出现唾液分泌不足和FLS，其中口腔不良菌群起着重要作用。这一发现表明口腔不良生物可能是治疗目标。