Enhancing Periodontal Outcomes with Genomics and Functional Medicine: A Case Report

Mary Ellen S. Chalmers, DMD, MS, IFMCP; Clare Cattarin, MSN, FNP, IFMCP

Mary Ellen S. Chalmers, DMD, MS, IFMCP, Private practice clinician; IFM Educator; Co-Founder Institute for Functional Dentistry; Institute for Functional Dentistry; Santa Rosa, California, USA. Clare Cattarin, MSN, FNP, IFMCP, Private Practice Clinician; San Francisco, California, USA.

Corresponding author: Mary Ellen S. Chalmers, DMD, MS  

E-mail: drchalmers@meschalmers.com

Keywords: Periodontal Disease, Genomics, Functional Medicine.

Introduction

Persistent, treatment-resistant periodontitis is one of the most clinically challenging presentations in dental practice. Conventionally, periodontal disease has been attributed to pathogenic oral bacteria, and treatment is directed accordingly—toward microbial reduction through mechanical debridement, antimicrobial adjuncts, and surgical intervention.^3,12 However, a growing body of evidence is shifting this paradigm. It is not periodontal pathogens alone that determine disease severity and progression; instead, the host’s inflammatory response drives tissue destruction.^2,8,16 In susceptible individuals, an exaggerated, poorly regulated immune response leads to a cytokine cascade—particularly IL-1α, IL-1β, and IL-6, responsible for alveolar bone loss and attachment destruction, even in the presence of excellent oral hygiene and low pathogenic burden.^6,14,18

When periodontal disease persists despite meticulous local therapy, we must look upstream—beyond the sulcus—toward systemic and genetic factors predisposing the host to dysregulated inflammation.^10,11 Single nucleotide polymorphisms (SNPs) in cytokine genes, vitamin D receptors, detoxification pathways, and immune-modulating genes can collectively prime a pro-inflammatory terrain that scaling, root planing, laser disinfection, and ozone therapy cannot adequately address on their own.^4,5,7,9

This case presents a patient with longstanding, treatment-resistant periodontitis, minimal pathogenic burden, excellent lifestyle habits, and progressive bone loss, demonstrating how genomic profiling using broad-based testing, interpreted within a functional medicine framework, can help identify actionable root-cause targets and improve surgical predictability.^9,19

Case Report

Patient Main Concerns, Diagnoses, and Important Clinical Findings

The patient is a healthy 65-year-old woman with a longstanding history of “sensitive gums” and progressive periodontal bone loss despite consistent, compliant care. She presented concerns about continued deterioration despite exemplary oral health and lifestyle care. Her periodontal diagnosis was Stage III, Grade B generalized periodontitis with localized Stage IV involvement.¹⁷

Pre-treatment clinical radiographic examination revealed a moderate to advanced uniform horizontal bone loss. Gingival tissues appeared relatively healthy with minimal visible inflammation and limited bleeding on probing—findings are inconsistent with the degree of structural bone loss present.¹³ Periodontal pocket depths ranged from 4–8 mm, with 6–8 mm pockets localized to the maxillary left lateral incisor and molar sites in the upper right, upper left, and lower left quadrants. The mismatch between modest gingival inflammation and significant bone destruction was a critical diagnostic signal.¹⁸

The patient had received quarterly supportive periodontal therapy—scaling and root planing, diode laser disinfection, and ozone treatment—for five years without meaningful improvement. Quantitative DNA-PCR oral microbiome testing identified only minor levels of five periodontal pathogens, none of them warranting systemic antibiotic therapy.^3,12 This finding, combined with years of failed conventional treatment, redirected the diagnostic lens to host immune-driven disease.^2,15,16 A periodontist confirmed the need for surgical intervention, and broad-based genomic testing was ordered to identify modifiable host factors to optimize surgical prognosis.^4,5

Interventions and Outcomes

Genomic testing identified clinically significant genetic variants across five panels directly relevant to periodontal susceptibility. The patient carried HLA-DQ8, conferring systemic immune activation and elevated celiac/gluten sensitivity risk.¹ Multiple vitamin D receptor (VDR) polymorphisms—including FokI, BsmI, ApaI, and TaqI variants—signaled impaired vitamin D–VDR signaling with downstream compromise of immune regulation, calcium metabolism, and bone homeostasis.^4,9 Inflammatory cytokine variants included IL-1α, IL-1β, and IL-6, collectively associated with exaggerated pro-inflammatory responses to oral and systemic insults.^6,7,14 Osteoporosis-related SNPs were present but modestly expressed. Detoxification variants compromised glutathione production and toxin clearance.^9,20,21 CCL2 homozygosity—an inflammatory variant driving monocyte recruitment and immune cell infiltration—further reinforced a genomic profile primed toward exaggerated, poorly resolved inflammation independent of pathogenic burden.^6,16

Lifestyle interventions were affirmed and refined. The foundation remained an organic, nutrient-dense, low-glycemic, whole-food diet.^9,11 Gluten was eliminated, given her HLA-DQ8 status.¹ Weight training- three days per week, and cardiovascular exercise- one to two days per week, continued. Sleep quality was monitored, and stress reduction was reinforced through daily box breathing and mindfulness meditation.⁹

Genomics-targeted nutraceuticals were layered onto this lifestyle foundation. To address IL-1/IL-6 cytokine hyperactivation, specialized pro-resolving mediators (SPMs) and palmitoylethanolamide were introduced to resolve chronic inflammation.¹⁹ Sulforaphane glucosinolate was added to support VDR function, enhance detoxification via Nrf2 activation, and modulate NF-κB signaling.^19,20 Pyrroloquinoline quinone (PQQ) was introduced to support mitochondrial resilience, and targeted probiotics addressed gut-oral axis dysbiosis.⁹ Liposomal glutathione, N-Acetyl Cysteine (NAC), resveratrol, and vitamin C were provided to support detoxification. Vitamin K2, hydrolyzed collagen, and optimized vitamin D were given to address osteoporosis SNPs and VDR-mediated bone metabolism.^9,19 Table 1 illustrates targeted genomic interventions.

Table 1. Clinical Interventions

Following these pre-surgical interventions, the patient experienced a clinically remarkable post-operative course—minimal swelling, no bruising, rapid recovery, and exceptional bone graft integration. Pocket depths closed significantly, and bleeding on probing was substantially reduced beyond anything achieved in the preceding five years of conventional therapy.¹⁹ Critically, when SPMs were discontinued six months post-surgery, regression in bone graft height necessitated a second surgical intervention—underscoring the likely essential ongoing role of pro-resolution signaling in graft maintenance.¹⁹ No adverse events occurred, and microcurrent therapy was integrated post-operatively throughout the collaborative care process.

Conclusion

This case illustrates that persistent, treatment-resistant periodontitis in a behaviorally compliant patient should prompt a fundamental reframing of the diagnostic question. When pathogenic burden is low and local therapy has been optimized, the clinician must ask: What is it about this host that perpetuates destruction? Genomic profiling provided a precise and actionable answer—identifying dysregulated inflammatory cytokine signaling, impaired vitamin D–VDR axis function, compromised detoxification capacity, and celiac-associated immune activation as root-cause antecedents driving tissue destruction despite excellent local care.

For periodontists and dental clinicians, treating refractory inflammatory periodontitis can be profoundly frustrating when predictable results remain elusive. This case suggests that a genomics-informed, functional medicine approach can meaningfully shift clinical trajectory when conventional therapy has plateaued. By mapping broad-based polymorphisms to targeted nutritional, nutraceutical, and lifestyle interventions, host response shifted toward resolution—with clinically important reductions in probing depths, bleeding, and surgical healing sequelae, with no observed harms.

Graft regression upon cessation of SPMs is compelling and instructive: pro-resolution biology should be actively maintained, not treated as a short-term perioperative adjunct. These findings support future research on stratifying periodontal patients by genomic and functional medicine antecedents, and exploring how genomics-informed care may reduce reliance on costly surgical intervention in inflammation-dominant cases.

Funding

No specific funding was received from any funding bodies in the public, commercial or not-for-profit sectors to carry out the work described in this manuscript.

References

1. Lucchese A, Di Stasio D, De Stefano S, Nardone M, Carinci F. Beyond the Gut: A Systematic Review of Oral Manifestations in Celiac Disease. J Clin Med. 2023;12(12):3874. doi:10.3390/jcm12123874
2. Loos BG, Van Dyke TE. The role of inflammation and genetics in periodontal disease. Periodontol 2000. 2020;83(1):26-39. doi:10.1111/prd.12297
3. Hajishengallis G, Lamont RJ. Polymicrobial communities in periodontal disease: their quasi-organismal nature and dialogue with the host. Periodontol 2000. 2021;86(1):210-230. doi:10.1111/prd.12371
4. Richter GM, Schaefer AS. Genetic susceptibility to periodontitis. J Periodontal Res. 2025;•••:jre.70002. doi:10.1111/jre.70002
5. Laine ML, Moustakis V, Koumakis L, Potamias G, Loos BG. Modeling susceptibility to periodontitis. J Dent Res. 2013;92(1):45-50. doi:10.1177/0022034512465435
6. de Alencar JB, Zacarias JMV, Tsuneto PY, et al. Influence of inflammasome NLRP3, and IL1B and IL2 gene polymorphisms in periodontitis susceptibility. PLoS One. 2020;15(1):e0227905. doi:10.1371/journal.pone.0227905
7. Levine M, Lohinai ZM. Innate immunity gene variants affect periodontitis susceptibility. Adv Exp Med Biol. 2026;1492:485-507. doi:10.1007/978-3-032-03176-1_23
8. Meyle J, Chapple I. Molecular aspects of the pathogenesis of periodontitis. Periodontol 2000. 2015;69(1):7-17. doi:10.1111/prd.12104
9. Sabine Elisabeth G, Yuxi Z, Jiawen Y, Lei W, Sabine R, Joerg M. Systemic, lifestyle and environmental modifying factors in the pathogenesis of periodontitis. J Periodontal Res. 2025;•••:jre.70003. doi:10.1111/jre.70003
10. Knight ET, Liu J, Seymour GJ, Faggion CM Jr, Cullinan MP. Risk factors that may modify the innate and adaptive immune responses in periodontal diseases. Periodontol 2000. 2016;71(1):22-51. doi:10.1111/prd.12110
11. Genco RJ, Borgnakke WS. Risk factors for periodontal disease. Periodontol 2000. 2013;62(1):59-94. doi:10.1111/j.1600-0757.2012.00457.x
12. Sedghi LM, Bacino M, Kapila YL. Periodontal disease: the good, the bad, and the unknown. Front Cell Infect Microbiol. 2021;11:766944. doi:10.3389/fcimb.2021.766944
13. Khocht A, Albandar JM. Aggressive forms of periodontitis secondary to systemic disorders. Periodontol 2000. 2014;65(1):134-148. doi:10.1111/prd.12015
14. Ferenc K, Bożek A, Gawron K. Immunological pathways triggered by Porphyromonas gingivalis in periodontitis: new insights into molecular mechanisms. Mol Immunol. 2026;189:119-132. doi:10.1016/j.molimm.2025.12.001
15. Nabiyeva Çevik N, Berker E, Tezcan I, Cagdas D. Inborn errors of immunity-related immunological mechanisms and pharmacological therapy alternatives in periodontitis. Clin Exp Immunol. 2025;219(1):uxae089. doi:10.1093/cei/uxae089
16. López-Valverde N, Quispe-López N, Blanco Rueda JA. Inflammation and immune response in the development of periodontal disease: a narrative review. Front Cell Infect Microbiol. 2024;14:1493818. doi:10.3389/fcimb.2024.1493818
17. Benahmed AG, Gasmi A, Noor S, et al. Hallmarks of Periodontitis. Curr Med Chem. 2025;32(14):2731-2749. doi:10.2174/0109298673302701240509103537
18. Zhang M, Liu Y, Afzali H, Graves DT. An update on periodontal inflammation and bone loss. Front Immunol. 2024;15:1385436. doi:10.3389/fimmu.2024.1385436
19. Balta MG, Papathanasiou E, Blix IJ, Van Dyke TE. Host modulation and treatment of periodontal disease. J Dent Res. 2021;100(8):798-809. doi:10.1177/0022034521995157
20. Larsson L, Giraldo-Osorno PM, Garaicoa-Pazmino C, Giannobile WV, Asa’ad F. DNA and RNA Methylation in Periodontal and Peri-implant Diseases. J Dent Res. 2025;104(2):131-139. doi:10.1177/00220345241291533
21. Pawlowska E, Szczepanska J, Derwich M, Sobczuk P, Düzgüneş N, Blasiak J. DNA Methylation in Periodontal Disease: A Focus on Folate, Folic Acid, Mitochondria, and Dietary Intervention. Int J Mol Sci. 2025;26(7):3225. doi:10.3390/ijms26073225
22. Chen I-Y, Moriyama M, Chang M-F, Ichinohe T. Severe acute respiratory syndrome coronavirus viroporin 3a activates the NLRP3 inflammasome. Front Microbiol. 2019;10:50. doi:10.3389/fmicb.2019.00050
23. Lopategi A, Flores-Costa R, Rius B, et al. Frontline Science: specialized proresolving lipid mediators inhibit the priming and activation of the macrophage NLRP3 inflammasome. J Leukoc Biol. 2019;105(1):25-36. doi:10.1002/JLB.3HI0517-206RR
24. Joffre C, Rey C, Layé S. N-3 polyunsaturated fatty acids and the resolution of neuroinflammation. Front Pharmacol. 2019;10:1022. doi:10.3389/fphar.2019.01022
25. Alshelh Z, Mills EP, Kosanovic D, et al. Effects of the glial modulator palmitoylethanolamide on chronic pain intensity and brain function. J Pain Res. 2019;12:2427-2439. doi:10.2147/JPR.S209657
26. Orefice NS, Alhouayek M, Carotenuto A, et al. Oral palmitoylethanolamide treatment is associated with reduced cutaneous adverse effects of interferon-β1a and circulating proinflammatory cytokines in relapsing-remitting multiple sclerosis. Neurotherapeutics. 2016;13(2):428-438. doi:10.1007/s13311-016-0420-z
27. Hennig P, Garstkiewicz M, Grossi S, Di Filippo M, French LE, Beer HD. The crosstalk between Nrf2 and inflammasomes. Int J Mol Sci. 2018;19(2):562. doi:10.3390/ijms19020562
28. ABCC1 gene – MRP1 protein. GeneCards Human Gene Database. Accessed February 3, 2021. https://www.genecards.org/cgi-bin/carddisp
29. Tian M, Xu X, Hu H, Liu Y, Pan S. Optimisation of enzymatic production of sulforaphane in broccoli sprouts and their total antioxidant activity at different growth and storage days. J Food Sci Technol. 2017;54(1):209-218. doi:10.1007/s13197-016-2452-0
30. Dias IH, Chapple IL, Milward M, et al. Sulforaphane restores cellular glutathione levels and reduces chronic periodontitis neutrophil hyperactivity in vitro. PLoS One. 2013;8(6):e66407. doi:10.1371/journal.pone.0066407
31. Houghton CA, Fassett RG, Coombes JS. Sulforaphane and other nutrigenomic Nrf2 activators: can the clinician’s expectation be matched by the reality? Oxid Med Cell Longev. 2016;2016(1):7857186. doi:10.1155/2016/7857186
32. Jonscher KR, Chowanadisai W, Rucker RB. Pyrroloquinoline quinone is more than an antioxidant: a vitamin-like accessory factor important in health and disease prevention. Biomolecules. 2021;11(10):1441. doi:10.3390/biom11101441
33. de Moreno de Leblanc A, Del Carmen S, Zurita-Turk M, et al. Importance of IL-10 modulation by probiotic microorganisms in gastrointestinal inflammatory diseases. ISRN Gastroenterol. 2011;2011:892971. doi:10.5402/2011/892971
34. Aljada B, Zohni A, El-Matary W. The gluten-free diet for celiac disease and beyond. Nutrients. 2021;13(11):3993. doi:10.3390/nu13113993
35. Öztekin Y, Güneş FE, Özen Alahdab Y. The investigation of nutritional status, intestinal permeability, and quality of life in people with celiac disease. Turk J Gastroenterol. 2022;33(12):1043-1049. doi:10.5152/tjg.2022.21815
36. Knowles L, Morris AAM, Walter JH. Treatment with mefolinate (5-methyltetrahydrofolate), but not folic acid or folinic acid, leads to measurable 5-methyltetrahydrofolate in cerebrospinal fluid in methylenetetrahydrofolate reductase deficiency. JIMD Rep. 2016;29:103-107. doi:10.1007/8904_2016_529
37. Health Quality Ontario. Vitamin B12 and cognitive function: an evidence-based analysis. Ont Health Technol Assess Ser. 2013;13(23):1-45.
38. Paul C, Brady DM. Comparative bioavailability and utilization of particular forms of B12 supplements with potential to mitigate B12-related genetic polymorphisms. Integr Med (Encinitas). 2017;16(1):42-49.
39. Zinck JW, de Groh M, MacFarlane AJ. Genetic modifiers of folate, vitamin B-12, and homocysteine status in a cross-sectional study of the Canadian population. Am J Clin Nutr. 2015;101(6):1295-1304. doi:10.3945/ajcn.115.107219
40. Sinha R, Sinha I, Calcagnotto A, et al. Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function. Eur J Clin Nutr. 2018;72(1):105-111. doi:10.1038/ejcn.2017.132
41. Waly MI, Al-Attabi Z, Guizani N. Low nourishment of vitamin C induces glutathione depletion and oxidative stress in healthy young adults. Prev Nutr Food Sci. 2015;20(3):198-203. doi:10.3746/pnf.2015.20.3.198
42. Idosa BA, Sahdo B, Balcha E, Kelly A, Söderquist B, Särndahl E. C10X polymorphism in the CARD8 gene is associated with bacteraemia. Immun Inflamm Dis. 2014;2(2):92-99. doi:10.1002/iid3.14
43. Andia DC, de Oliveira NFP, Letra AM, Nociti FH Jr, Line SRP, de Souza AP. Interleukin-8 gene promoter polymorphism (rs4073) may contribute to chronic periodontitis. J Periodontol. 2011;82(6):893-899. doi:10.1902/jop.2010.100513