Oral microbiome and metabolome in type 2 diabetes mellitus patients:  A systematic review.

Dr. Dinesh Kumar   Ravi; Dr.Karthik  Shunmugavelu; Pushpa  H

doi:10.51168/sjhrafrica.v7i3.2471

Authors

Dr. Dinesh Kumar Ravi M.B.B.S., MD., FID., PGDEM, PSP Medical College Hospital and Research Institute, Tambaram, Kanchipuram main road, Oragadam, Panruti, Kanchipuram district Tamilnadu 631604 India
Dr.Karthik Shunmugavelu Assistant Professor, Department of Dentistry, PSP Medical College Hospital and research institute, Tambaram, Kanchipuram Main Road, Oragadam, Panruti, Kanchipuram district, Tamilnadu 631604 India
Pushpa H Undergraduate (MBBS), PSP Medical College Hospital and Research Institute, Tambaram, Kanchipuram main road, Oragadam, Panruti, Kanchipuram district Tamilnadu 631604 India

DOI:

https://doi.org/10.51168/sjhrafrica.v7i3.2471

Keywords:

oral microbiome, oral metabolome, type 2 diabetes mellitus, oral biomarkers

Abstract

Introduction

Type 2 diabetes mellitus (T2DM) is one of the leading metabolic disorders worldwide and is associated with multiple systemic complications. Increasing evidence indicates that diabetes alters the composition and metabolic activity of the oral microbiota. The oral microbiome and its associated metabolome may therefore serve as indicators of disease status and for biomarker discovery. This systematic review evaluates the current evidence on alterations in the oral microbiome and metabolome in patients with T2DM.

Methods

A systematic search was conducted following PRISMA guidelines. Electronic databases, including PubMed, MEDLINE, Scopus, Embase, Web of Science, and LILACS, were searched for studies published between 2020 and 2024. Search terms included “oral microbiome,” “metabolome,” and “type 2 diabetes mellitus.” Eligible studies investigated associations between oral microbial composition and metabolic profiles in T2DM patients. Data extracted included author, year, country, study design, and key outcomes. Study quality was evaluated using the STROBE checklist.

Results

Four original research studies met the inclusion criteria. The included studies consistently reported alterations in oral microbial composition and metabolic profiles in individuals with T2DM. Changes were observed in bacterial abundance and in metabolite profiles associated with carbohydrate metabolism, inflammatory pathways, and host–microbe interactions. Some studies identified correlations between glycemic control and shifts in microbial diversity and metabolite production. These findings indicate that metabolic changes in the oral environment may influence microbial ecology and disease susceptibility.

Conclusion

Evidence suggests that T2DM is associated with measurable alterations in the oral microbiome and metabolome. These changes may contribute to oral dysbiosis and may have implications for early detection of metabolic and oral complications.

Future research

Large-scale longitudinal studies integrating metagenomics and metabolomics are required to validate oral biomarkers and clarify the mechanistic relationship between diabetes, microbial dysbiosis, and metabolic alterations.

References

Diao J, Zhang Y, Zhang X, Jia S, Lei Y, Ma B, et al. Integrated analysis of oral microbiome and metabolome in T2DM patients with varying glycemic status. Oral Dis. 2024 Dec 17; https://doi.org/10.1111/odi.15220 PMid:39688114

Fang X, Miao R, Wei J, Wu H, Tian J. Advances in multi-omics study of biomarkers of glycolipid metabolism disorder. Comput Struct Biotechnol J. 2022 Jan 1;20:5935-51. https://doi.org/10.1016/j.csbj.2022.10.030 PMid:36382190 PMCid:PMC9646750

Li Y, Qian F, Cheng X, Wang D, Wang Y, Pan Y, et al. Dysbiosis of oral microbiota and metabolite profiles associated with type 2 diabetes mellitus. Microbiol Spectr. 2023 Feb 14;11(1):e03796-22. https://doi.org/10.1128/spectrum.03796-22 PMid:36625596 PMCid:PMC9927158

Almeida-Santos A, Martins-Mendes D, Gayà-Vidal M, Pérez-Pardal L, Beja-Pereira A. Characterization of the oral microbiome of medicated type-2 diabetes patients. Front Microbiol. 2021 Feb 5;12: 610370. https://doi.org/10.3389/fmicb.2021.610370 PMid:33613481 PMCid:PMC7892904

Kilian M. The oral microbiome: friend or foe? Eur J Oral Sci. 2018 Oct;126:5-12.https://doi.org/10.1111/eos.12527 PMid:30178561

Dewhirst FE, Chen T, Izard J, Paster BJ, Tanner AC, Yu WH, et al. The human oral microbiome. J Bacteriol. 2010 Oct 1;192(19):5002-17. https://doi.org/10.1128/JB.00542-10 PMid:20656903 PMCid:PMC2944498

Radaic A, Kapila YL. The oralome and its dysbiosis: New insights into oral microbiome-host interactions. Comput Struct Biotechnol J. 2021 Jan 1;19:1335-60. https://doi.org/10.1016/j.csbj.2021.02.010 PMid:33777334 PMCid:PMC7960681

Zhang Y, Wang X, Li H, Ni C, Du Z, Yan F. Human oral microbiota and its modulation for oral health. https://doi.org/10.1016/j.biopha.2018.01.146 PMid:29710488

Deo PN, Deshmukh R. Oral microbiome: Unveiling the fundamentals. J Oral Maxill Pathol. 2019 Jan 1;23(1):122-8. https://doi.org/10.4103/jomfp.JOMFP_304_18 PMid:31110428 PMCid:PMC6503789

Johansson I, Witkowska E, Kaveh B, Lif Holgerson P, Tanner AC. The microbiome in populations with a low and high prevalence of caries. J Dent Res. 2016;95(1):80-6. https://doi.org/10.1177/0022034515609554 PMid:26442950 PMCid:PMC4700664

Takahashi N. Oral microbiome metabolism: from "who are they?" to "what are they doing?". J Dent Res. 2015 Dec;94(12):1628-37. https://doi.org/10.1177/0022034515606045 PMid:26377570

Vangipurapu J, Fernandes Silva L, Kuulasmaa T, Smith U, Laakso M. Microbiota-related metabolites and the risk of type 2 diabetes. Diab Care. 2020 Jun 1;43(6):1319-25. https://doi.org/10.2337/dc19-2533 PMid:32295805

Graves DT, Corrêa JD, Silva TA. The oral microbiota is modified by systemic diseases. J Dent Res. 2019 Feb;98(2):148-56. https://doi.org/10.1177/0022034518805739 PMid:30359170 PMCid:PMC6761737

Liu YK, Chen V, He JZ, Zheng X, Xu X, Zhou XD. A salivary microbiome-based auxiliary diagnostic model for type 2 diabetes mellitus. Arch Oral Biol. 2021 Jun 1;126:105118. https://doi.org/10.1016/j.archoralbio.2021.105118 PMid:33930650

Negrini TD, Carlos IZ, Duque C, Caiaffa KS, Arthur RA. Interplay among the oral microbiome, oral cavity conditions, the host immune response, diabetes mellitus, and its associated-risk factors: An overview. Front Oral Health. 2021 Sep 9;2:697428. https://doi.org/10.3389/froh.2021.697428 PMid:35048037 PMCid:PMC8757730

Bencharit S, Carlson J, Byrd WC, Howard-Williams EL, Seagroves JT, McRitchie S, et al. Salivary metabolomics of well and poorly controlled type 1 and type 2 diabetes. Int J Dent. 2022;2022(1):7544864. https://doi.org/10.1155/2022/7544864 PMid:36059915 PMCid:PMC9433218

Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018;14(2):88-98. https://doi.org/10.1038/nrendo.2017.151 PMid:29219149

Peng X, Cheng L, You Y, Tang C, Ren B, Li Y, Xu X, Zhou X. Oral microbiota in human systemic diseases. Int J Oral Sci. 2022 Dec;14(1):14. https://doi.org/10.1038/s41368-022-00163-7 PMid:35236828 PMCid:PMC8891310

Jin Q, Ma RC. Metabolomics in diabetes and diabetic complications: insights from epidemiological studies. Cells. 2021 Oct 21;10(11):2832. https://doi.org/10.3390/cells10112832 PMid:34831057 PMCid:PMC8616415

Chen B, Wang Z, Wang J, Su X, Yang J, Zhang Q, Zhang L. The oral microbiome profile and biomarker in Chinese type 2 diabetes mellitus patients. Endocrin. 2020 Jun;68:564-72. https://doi.org/10.1007/s12020-020-02269-6 PMid:32246318

Chen ZZ, Gerszten RE. Metabolomics and proteomics in type 2 diabetes. Circ Res. 2020 May 22;126(11):1613-27. https://doi.org/10.1161/CIRCRESAHA.120.315898 PMid:32437301 PMCid:PMC11118076

Beagley J, Guariguata L, Weil C, Motala AA. Global estimates of undiagnosed diabetes in adults. Diabetes Res Clin Pract. 2014 Feb;103(2):150-60. https://doi.org/10.1016/j.diabres.2013.11.001 PMid:24300018

Ohlrich EJ, Cullinan MP, Leichter JW. Diabetes, periodontitis, and the subgingival microbiota. J Oral Microbiol. 2010 Dec 21:2. https://doi.org/10.3402/jom.v2i0.5818 PMid:21523215 PMCid:PMC3084563

Ortiz-Martínez M, González-González M, Martagón AJ, Hlavinka V, Willson RC, Rito-Palomares M. Recent developments in biomarkers for diagnosis and screening of type 2 diabetes mellitus. Curr Diab Rep. 2022 Mar;22(3):95-115. https://doi.org/10.1007/s11892-022-01453-4 PMid:35267140 PMCid:PMC8907395

Schrader S, Perfilyev A, Ahlqvist E, Groop L, Vaag A, Martinell M, et al. Novel subgroups of type 2 diabetes display different epigenetic patterns that associate with future diabetic complications. Diabetes Care. 2022 Jul 7;45(7):1621-30. https://doi.org/10.2337/dc21-2489 PMid:35607770 PMCid:PMC9274219

Sarría-Santamera A, Orazumbekova B, Maulenkul T, Gaipov A, Atageldiyeva K. The identification of diabetes mellitus subtypes applying cluster analysis techniques: A systematic review. Int J Environ Res Public Health. 2020 Dec 18;17(24):9523. https://doi.org/10.3390/ijerph17249523 PMid:33353219 PMCid:PMC7766625

Pauling L., Robinson A.B., Teranishi R., Cary P. Quantitative analysis of urine vapor and breath by gas-liquid partition chromatography. Proc. Natl. Acad. Sci. USA. 1971;68:2374-2376. https://doi.org/10.1073/pnas.68.10.2374 PMid:5289873 PMCid:PMC389425

Deo PN, Deshmukh R. Oral microbiome: Unveiling the fundamentals. J Oral Maxillofac Pathol. 2019 Jan-Apr;23(1):122-8. https://doi.org/10.4103/jomfp.JOMFP_304_18 PMid:31110428 PMCid:PMC6503789

Zhao X, Chen X, Lu Y, Zhou Z, Lin P, Lin Y, Hu S, Cui L. Saliva metabolomics: a non-invasive frontier for diagnosing and managing oral diseases. J Transl Med. 2025 May 24;23(1):582. https://doi.org/10.1186/s12967-025-06587-z PMid:40413543 PMCid:PMC12102935