Association of Bitter Taste Receptor T2R38 Polymorphisms, Oral Microbiota, and Rheumatoid Arthritis Original paper
Researched by:
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Kimberly Eyer
ID
Kimberly Eyer
Kimberly Eyer, a Registered Nurse with 30 years of nursing experience across diverse settings, including Home Health, ICU, Operating Room Nursing, and Research. Her roles have encompassed Operating Room Nurse, RN First Assistant, and Acting Director of a Same Day Surgery Center. Her specialty areas include Adult Cardiac Surgery, Congenital Cardiac Surgery, Vascular Surgery, and Neurosurgery.
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Rheumatoid Arthritis
Rheumatoid Arthritis
OverviewRheumatoid arthritis (RA) is a systemic autoimmune disease marked by chronic joint inflammation, synovitis, and bone erosion, driven by Treg/Th17 imbalance, excessive IL-17, TNF-α, and IL-1 production, and macrophage activation. Emerging evidence links microbial dysbiosis and heavy metal exposure to RA, [1][2] with gut microbiota influencing autoimmune activation via Toll-like receptor (TLR) signaling, inflammasome activation, […]
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Kimberly Eyer
Researched by:
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Kimberly Eyer
ID
Kimberly Eyer
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Kimberly Eyer
What was studied?
This study examined the relationship between T2R38 bitter taste receptor gene polymorphisms, the composition of the oral microbiota, and rheumatoid arthritis (RA) status. Specifically, it assessed whether the T2R38 genotypes (PAV/PAV, PAV/AVI, AVI/AVI) influenced the buccal microbial community and whether this interaction was associated with RA pathogenesis or oral microbial dysbiosis.
Who was studied?
The study involved 99 adults, including 35 individuals with clinically diagnosed RA and 64 non-RA controls. Most of the non-RA participants were first-degree relatives of the RA patients, considered at-risk individuals. Buccal swabs were collected from all participants for both genotyping of the TAS2R38 gene and 16S rRNA sequencing of the oral microbiome. Clinical features, inflammatory markers, and periodontal health symptoms were also recorded.
What were the most important findings?
The study revealed significant shifts in the buccal microbiome between RA and non-RA individuals, independent of diversity indices. RA patients exhibited higher relative abundances of Streptococcus salivarius, Rothia mucilaginosa, and Leptotrichia, whereas non-RA individuals showed enrichment in Porphyromonas, Fusobacterium periodonticum, Aggregatibacter, and Capnocytophaga. These genera are known to modulate inflammation and mucosal immunity, aligning with recognized dysbiosis in RA.
Crucially, the TAS2R38 genotype modified the oral microbial profile. Supertasters (PAV/PAV) with RA had higher levels of Streptococcus salivarius—a known immunomodulatory commensal—compared to non-tasters (AVI/AVI). Conversely, Porphyromonas and Aggregatibacter, associated with periodontal disease and implicated in ACPA production, were depleted in RA. These findings suggest that T2R38 polymorphisms, which influence oral mucosal immunity through differential antimicrobial peptide expression, may shape oral microbial ecology in RA.
| Feature | Finding | Implication |
|---|---|---|
| RA-associated taxa | ↑ Streptococcus salivarius, Rothia mucilaginosa, Leptotrichia | Indicators of RA-specific dysbiosis and mucosal immune adaptation |
| Non-RA-enriched taxa | ↑ Porphyromonas, Fusobacterium, Aggregatibacter | Suggest immune exclusion of periodontal pathogens in RA |
| Genotype-microbiome interaction | PAV/PAV RA patients had ↑ Streptococcus salivarius | TAS2R38-mediated modulation of oral immunity |
| T2R38 polymorphism distribution | Overrepresentation of PAV/PAV in RA vs. published population controls | Suggests genetic predisposition influencing oral-immune axis in RA |
| Implications for ACPA development | Depletion of P. gingivalis and Aggregatibacter in established RA | Potential early immune targeting of citrullinating pathogens prior to disease onset |
| Alpha diversity | No significant differences by RA status or T2R38 genotype | Dysbiosis not reflected in richness but in compositional shifts |
| Beta diversity | Significant difference between RA and non-RA (p = 0.02) | Confirms distinct microbial communities between groups |
| Clinical translation | Supports microbiome-genotype risk models for RA; possible diagnostic and therapeutic value | May inform MBTI development targeting host-microbiome interactions mediated by taste receptors |
What are the greatest implications of this study?
This study provides novel evidence linking taste receptor polymorphisms, specifically TAS2R38, to oral microbiome composition and RA susceptibility. The differential microbial signatures observed—particularly the RA-associated depletion of periodontal pathogens in PAV/PAV individuals—support the idea that heightened T2R38-mediated immune surveillance may selectively modulate oral dysbiosis. This could have implications for early immune priming and autoantibody production via citrullination pathways involving P. gingivalis and A. actinomycetemcomitans.
For the Microbiome Signatures Database, this study contributes to defining RA-specific Major Microbial Associations (MMAs) in the oral cavity. Clinically, it highlights the potential of integrating genotypic screening (e.g., TAS2R38) with microbiome profiling as a stratification tool in RA risk assessment and precision therapeutics. It also supports future development of microbiome-targeted interventions (MBTIs) aimed at restoring oral eubiosis in genetically susceptible individuals.