Linking Salivary Extracellular Vesicle-Derived MicroRNAs to Metabolism and Taste Sensation

Research Question: Extracellular vesicles (EVs) hold significant medical prospect as carriers of molecules like microRNAs for targeted therapeutic and diagnostic purposes on a cellular level. In the context of obesity research, EVs have gathered attention for their potential role in influencing parameters such as eating behaviour and we could previously show a reduced number of salivary EVs among patients with obesity. This study explores the link between salivary EV derived miRNAs and metabolic parameters including factors of taste perception.

Objectives: Salivary EVs were isolated and used for RNA sequencing to identify a correlation with metabolic changes in obesity, alterations in taste perception, and addresses pathway enrichment analyses. Therefore, N=90 subjects from the Obese Taste Bud Study were enrolled for qualitative analyses of salivary EVs.

Methods: Using size exclusion chromatography, EVs were isolated from 2 ml saliva per subject. RNA extraction was carried out using the miRNeasy Micro Kit with subsequent sequencing on the NovaSeq6000 platform for qualitative assessment of the RNA content. Known and novel miRNAs were identified using mirTOP and mirDeep2 from a final number of 63 participants. To explore patterns and variability within the microRNA dataset, principal component analysis (PCA) was performed in R and further correlation analyses proofed associations of enriched miRNAs with metabolic and parameters of taste sensation. Pathway enrichment analyses were conducted using the miRNA Enrichment Analysis and Annotation Tool to highlight the potentially biologically significant pathways of EV-derived miRNAs.

Results: Small RNA-Seq analysis revealed that 64% of the RNA content extracted from the EVs consisted of ribosomal RNAs (rRNAs), while microRNAs (miRNAs) accounted for 7%, and messenger RNAs (mRNAs) made up 6%, highlighting the diverse RNA composition within salivary EVs. A total number of 626 miRNAs were found in salivary EVs and are enriched in pathways related to overall metabolism, but also cell signalling, salivation, taste perception and appetite regulation. Among the top enriched microRNAs are well known obesity associated miRNAs such as let-7a-5p or miR1290 being related to fasting glucose level or anthropometrics in the presented dataset, respectively. Taste sum score and the ability to detect bitter explain a variability in the counts for miR26a-5p and miR6816-5p while others are related to parameters of oral health.

Conclusion: These findings provide valuable insights into the intricate interplay between EVs, taste perception, and obesity, contributing to the development of effective interventions for this burgeoning health concern. Ongoing analyses on how the microRNA composition of salivary EVs may affect taste buds might enlighten our understanding in alterations of taste and eating behaviour in obesity.

 

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Interessenkonflikt

MB received honoraria as a consultant and speaker from Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Daiichi-Sankyo, Lilly, Novo Nordisk, Novartis, Pfizer, and Sanofi. All other authors declare to have no conflict of interest.

Publication History

Article published online:
28 May 2025