The role of taste genetics and oral microbiome in severe early childhood caries
Cruz de Jesus, Vivianne
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Early childhood caries (ECC) and its more severe form S-ECC are prevalent diseases linked to various etiologic factors, including sex, microbiota, diet, and genetics. Recent studies have highlighted the role of inter-kingdom interactions involving fungi and cariogenic bacteria in the onset of dental caries. However, sex-specific and oral site-specific differences in the oral microbiome are poorly characterized. Evidence suggests that there is a plausible relationship between genetic variants in taste genes and enhanced ECC risk or protection. This has been attributed to the modulatory effect of bitter taste receptors on taste preferences and oral innate immune responses. Nevertheless, previous caries studies focused on select sweet and bitter taste receptors (T1Rs and T2Rs), with minimal or no attention to other taste signal transducing proteins such as free fatty acid receptors (FFARs), salt and sour ion channels (ENaCs and OTOP1), and carbonic anhydrases (CAs). Therefore, this study investigated whether variants in multiple taste genes play a role in S-ECC and the oral microbiome. The first part of the thesis focuses on characterizing the oral microbiome, identifying sex-specific and site-specific bacterial and fungal species that are associated with S-ECC. The second part evaluates the association of taste genetic variants with S-ECC and the dental plaque microbial composition. The third part investigates the role of seven genes, involved in downstream taste signaling, in S-ECC and dental biofilm composition. These studies demonstrate that sex- and site-specific differences in the oral microbiome exist. A significant difference in the abundance of Neisseria was observed between males and females with S-ECC. Streptococcus mutans, Candida albicans, and Candida dubliniensis, among others, were enriched in the dental plaque, compared to oral swabs, of children with S-ECC. Also, genetic variants in genes encoding proteins involved in taste sensations (SCNN1D, CA6, TAS2R3, OTOP1, TAS2R5, TAS2R60, TAS2R4, SCNN1B, FFAR3, TAS1R3, SCNN1G, CA7, TAS2R38, TAS2R41, TAS1R1) and downstream taste signaling components (PLCB2, GNAQ, GNAS, GNAT3, RALB, and RAC1) were associated with S-ECC and/or the composition of the bacterial and fungal microbiomes. Overall, these findings may improve our understanding of S-ECC etiology and help to develop more personalized predictive and preventative strategies.