Salivary Short-Chain Fatty Acids as a Window into Metabolic Dysregulation in Type 2 Diabetes

The gut microbiota-host metabolic axis has emerged as a key regulator of glucose homeostasis, with short-chain fatty acids (SCFAs) acting as bioactive metabolites influencing insulin sensitivity, inflammation, and energy balance. Altered SCFA production has been implicated in the pathophysiology of Type 2 diabetes mellitus (T2DM), yet noninvasive biomarkers reflecting these metabolic changes remain limited. Salivary SCFAs offer a novel and accessible medium to explore microbiota-related metabolic alterations in diabetes. This study aimed to assess and compare salivary concentrations of acetic acid and butyric acid in individuals with newly diagnosed T2DM and healthy controls and to explore their association with diabetic status.

A case-control study was conducted, including adults aged 45 to 65 years. Newly diagnosed T2DM patients were recruited based on the American Diabetes Association diagnostic criteria, whereas age-matched healthy individuals served as controls. Unstimulated whole saliva samples were collected using the Navazesh standardized protocol and stored at -80°C until analysis. Salivary acetic acid and butyric acid levels were quantified using competitive enzyme-linked immunosorbent assay kits. Statistical analysis was performed using SPSS version 23.0, with comparisons between groups assessed by unpaired t-test and correlations evaluated using the Pearson's correlation coefficient.

Salivary concentrations of acetic acid and butyric acid showed significant differences between T2DM subjects and healthy controls, indicating altered SCFA profiles in diabetic individuals. These variations suggest an association between impaired microbial fermentation activity and dysregulated glucose metabolism.

Altered salivary SCFA levels in T2DM highlight their potential role as noninvasive biomarkers, reflecting gut microbiota-host metabolic interactions. Salivary SCFA profiling may provide insight into metabolic dysregulation in diabetes and support future microbiota-targeted therapeutic strategies.