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

Abstract

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.

A murine periodontitis model using coaggregation between human pathogens and a predominant mouse oral commensal bacterium

“…We previously reported the predominance of simple oral microbiota in C57BL/6 mice by a phylotype designated Streptococcus EU453973_s, which accounted for up to 94% of the total bacteria [ 6 ]. This phylotype is identical to Streptococcus danieliae (Sd), which was later isolated in the mouse gut [ 7 ], and this species has also been found to predominate the oral microbiota of mice of the 129/Ola × C57BL/6 background [ 8 ]. We hypothesized that human periodontal pathogens coaggregating with the murine oral commensal Sd could colonize the mouse oral cavity and might cause persistent infection of gingival tissues.…”

Characterization of junctional structures in the gingival epithelium as barriers against bacterial invasion

“…Similarly, significantly reduced ZO-1 expression and increased bacterial invasion in the SE and OE of periodontal lesions have been reported. 13,14 Notably, the oral microbiota of the mice used in the current study is dominated by Streptococcus danieliae, 15 and S. danieliae has a low ability to invade oral keratinocytes compared with human periodontal pathogens. 29 Although abundant bacteria were detected in the granular layers of the SE and OE, only a few reached the lamina propria after passing through the spinous and basal layers (Figure 5D).…”

“…Mice were maintained under specific pathogen‐free conditions in the Laboratory Animal Facility at School of Dentistry, Seoul National University. C57BL/6 mice (Orient Bio) were used for field emission scanning electron microscopy (FE‐SEM), and wild‐type 129/Ola x C57BL/6 mice 15 were used for other experiments. Twenty‐week‐old mice were used.…”

A Glimpse Into the Microbiome of Sjögren’s Syndrome

“…For example, Lee et al. found that cohousing young Nfkbiz+/+ with Nfkbiz−/− mice synchronized their oral microbiome toward that of young Nfkbiz+/+ mice, preventing dysbiosis of Nfkbiz−/− mice ( 28 ). Further, Zaheer et al.…”