Abstract
BACKGROUND: The rising prevalence of Type 2 diabetes mellitus (T2D) in the Qatari population presents a significant public health challenge, highlighting the need for innovative approaches to early detection and management. While most efforts are centered on using blood samples for biomarker discovery, the use of saliva remains underexplored. METHODS: Using noninvasive saliva samples from 2974 Qatari subjects, we analyzed the microbial communities from diabetic, pre-diabetic, and non-diabetic participants based on their HbA1C levels. The salivary microbiota was assessed in all subjects by sequencing the V1-V3 regions of 16S rRNA gene. For the proteomics profiling, we randomly selected 50 gender and age-matched non-diabetic and diabetic subjects and compared their proteome with SOMAscan. Microbiota and proteome profiles were then integrated to reveal candidate biomarkers for T2D. RESULTS: Our results indicate that the salivary microbiota of pre-diabetic and diabetic individuals differs significantly from that of non-diabetic subjects. Specifically, a significant increase in the abundance of Campylobacter, Dorea, and Bacteroidales was observed in the diabetic subjects compared to their non-diabetic controls. Metabolic pathway prediction analysis for these bacteria revealed a significant overrepresentation of genes associated with fatty acid and lipid biosynthesis, as well as aromatic amino acid metabolism in the diabetic group. Additionally, we observed distinct differences in salivary proteomic profiles between diabetic and non-diabetic subjects. Notably, levels of Haptoglobin, Plexin-C1, and MCL-1 were elevated, while Osteopontin (SPP1), Histone1H3A (HIST3H2A), and Histone H1.2 were reduced in diabetic individuals. Furthermore, integrated correlation analysis of salivary proteome and microbiota data demonstrated a strong positive correlation between HIST1H3A and HIST3H2A with Porphyromonas sp., all of which were decreased in the diabetic group. CONCLUSION: This is the first study to assess the salivary microbiota in T2D patients from a large cohort of the Qatari population. We found significant differences in the salivary microbiota of pre-diabetic and diabetic individuals compared to non-diabetic controls. Our study is also the first to assess the salivary proteome using SOMAScan in diabetic and non-diabetic subjects. Integration of the microbiota and proteome profiles revealed a unique signature for T2D that can be used as potential T2D biomarkers.