Minoru Goda, Taro Mukaibo, Masahiro Sugimoto, Takashi Munemasa, Tomotaka Nodai, Yusuke Kondo, Ryuji Hosokawa, Chihiro Masaki
Salivary metabolite profiles only partially reflected gland-derived metabolic states, indicating that tissue-saliva relationships are shaped by compartment-specific processes under stimulated conditions. Given the limited sample size (n = 3 per group), these observations are preliminary and hypothesis-generating. Because the analysis was restricted to submandibular gland-derived saliva under ex vivo stimulation, the findings represent neither whole-mouth saliva nor in vivo conditions. The study provides a framework for interpreting salivary metabolomics data by considering contributing sources, secretion dynamics, and experimental context, rather than proposing biomarkers.
OBJECTIVES: This exploratory study used an ex vivo-perfused mouse submandibular gland model to characterize tissue-saliva metabolite relationships and age- and sex-associated variation.
DESIGN: Submandibular glands isolated from young adult and aged C57BL/6 J mice (n = 6 per group; 3 males and 3 females each) were perfused ex vivo, and salivary secretion was induced by combined cholinergic and β-adrenergic stimulation. Hydrophilic metabolites in glandular tissue and saliva were profiled by CE-TOFMS. Differential analyses used Mann-Whitney tests with Benjamini-Hochberg FDR correction. Total salivary metabolite secretion was calculated from metabolite concentration and total saliva volume normalized to gland weight.
RESULTS: Sex-associated differences were more evident in salivary gland tissue, with several metabolites differing significantly between sexes, whereas no significant differences were detected in saliva. In the pooled age comparison, no salivary metabolites reached statistical significance after FDR correction; however, choline was among the metabolites showing the strongest age-associated trends, with higher levels in young adult than aged mice. Tissue and salivary metabolite profiles showed only partial correspondence.
CONCLUSIONS: Salivary metabolite profiles only partially reflected gland-derived metabolic states, indicating that tissue-saliva relationships are shaped by compartment-specific processes under stimulated conditions. Given the limited sample size (n = 3 per group), these observations are preliminary and hypothesis-generating. Because the analysis was restricted to submandibular gland-derived saliva under ex vivo stimulation, the findings represent neither whole-mouth saliva nor in vivo conditions. The study provides a framework for interpreting salivary metabolomics data by considering contributing sources, secretion dynamics, and experimental context, rather than proposing biomarkers.