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Metatranscriptomics of the Human Oral Microbiome during Health and Disease
Open accessAbstract
The human microbiome plays important roles in health, but when disrupted, these same indigenous microbes can cause disease. The composition of the microbiome changes during the transition from health to disease; however, these changes are often not conserved among patients. Since microbiome-associated diseases like periodontitis cause similar patient symptoms despite interpatient variability in microbial community composition, we hypothesized that human-associated microbial communities undergo conserved changes in metabolism during disease. Here, we used patient-matched healthy and diseased samples to compare gene expression of 160,000 genes in healthy and diseased periodontal communities. We show that health- and disease-associated communities exhibit defined differences in metabolism that are conserved between patients. In contrast, the metabolic gene expression of individual species was highly variable between patients. These results demonstrate that despite high interpatient variability in microbial composition, disease-associated communities display conserved metabolic profiles that are generally accomplished by a patient-specific cohort of microbes. IMPORTANCE The human microbiome project has shown that shifts in our microbiota are associated with many diseases, including obesity, Crohn’s disease, diabetes, and periodontitis. While changes in microbial populations are apparent during these diseases, the species associated with each disease can vary from patient to patient. Taking into account this interpatient variability, we hypothesized that specific microbiota-associated diseases would be marked by conserved microbial community behaviors. Here, we use gene expression analyses of patient-matched healthy and diseased human periodontal plaque to show that microbial communities have highly conserved metabolic gene expression profiles, whereas individual species within the community do not. Furthermore, disease-associated communities exhibit conserved changes in metabolic and virulence gene expression.
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“Culture‐independent methods have improved our understanding of microbial diversity in the oral cavity.”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [14]
In the citing paper
“Application of transcriptomic approaches has proved extremely significant for delineating both microbial and host gene expression in the context of oral health and pathology.14, 68, 94”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [14]
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“However, despite dissimilar phylogeny, functional signatures among the oral microbiota are often conserved from one individual to another.13, 14”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [14]
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“7 Furthermore, there is clinical and histological evidence that topical application of lactic acid can be effective in depig-menting the skin, improving the surface roughness of the skin and reducing mild wrinkles caused by environmental photodamage.”
BackgroundMa, Y., Liu, G., Ma, Y., & Chen, Q. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00083 · Cited by 7
“For example, Jorth et al. have reported that gene expression pro fi les of periodontitis-related microbial communities have highly conserved changes, relative to healthy samples (Jorth et al., 2014).”
BackgroundIs Fluorescence Technology a Promising Tool for Detecting Infected Dentin in Deep Carious Lesions?
Trippe, L. H., Ribeiro, A. A., Azcárate-Peril, M. A., Preisser, J. S., Wang, R., & Zandoná, A. F. (2020) · Caries Research · doi:10.1159/000505643 · Cited by 7
“However, alterations in the microbiome caused by high carbohydrate consumption or plaque accumulation can lead to a shift in species and functions associated with diseases and, thus, dysbiosis such as dental caries and/or periodontal diseases [Marsh 1994, 2003; Belda-Ferre et al., 2012; Griffen et al., 2012; Wang et a…”
BackgroundDecoding Complex Soil Microbial Communities through New Age "Omics"
Nair, G. R., & Raja, S. S. (2017) · Journal of Microbial & Biochemical Technology · doi:10.4172/1948-5948.1000382 · Cited by 6
Asgari, E., Garakani, K., McHardy, A. C., & Mofrad, M. R. K. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/255018 · Cited by 7
Wang, J., Li, D., Wang, J., & Zhang, Z. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/732123 · Cited by 7
“However, the imbalances of microbial community in oral cavity can lead to the oral diseases, such as the dental caries, periodontitis, oral mucosal diseases and systemic diseases such as gastrointestinal and neurological diseases [2,4-13].”
BackgroundMetagenomic insights into the diversity and functions of microbial assemblages in lakes
Salam, L. B. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-817495-1.00005-0 · Cited by 6
Labossiere, A., Ramsey, M. M., Merritt, J. L., & Kreth, J. (2023) · mBio · doi:10.1128/mbio.01342-23 · Cited by 6
Byrne, S. J., Butler, C. A., Reynolds, E. C., & Dashper, S. G. (2018) · Methods in microbiology · doi:10.1016/bs.mim.2018.07.001 · Cited by 8
Microbiota in Periodontitis: Advances in the Omic Era
Fong, S. B., Boyer, É., Bonnaure‐Mallet, M., & Meuric, V. (2022) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-96881-6_2 · Cited by 6
The polymicrobial synergy and dysbiosis model of periodontal disease pathogenesis
Hajishengallis, G., & Lamont, R. J. (2016) · doi:10.1002/9781118982907.ch14 · Cited by 6
Wzatek, M., Bahammam, S., Buiga, P., Haddad, K., & Sima, C. (2022) · Frontiers in Oral Health · doi:10.3389/froh.2022.821326 · Cited by 5
“-3 binding to FFAR4 and derived SPMs, including RvE1 binding to ERV1, play important roles in the resolution of inflammation [3, 4].”
BackgroundIntestinal microbiome and modern methods of its study in children
Васильевна, В. Г., Nikitin, A. V., & Андреевна, С. Т. (2022) · Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) · doi:10.21508/1027-4065-2022-67-4-5-13 · Cited by 5
Griffith, J. C., & Morgan, X. C. (2019) · American Journal of Epidemiology · doi:10.1093/aje/kwz007 · Cited by 5
Integrative multi-omics analysis reveals oral microbiome-metabolome signatures of obesity
Shibl, A. A., Denekew, T. W., Ahmad, A. R., Abdelrazig, S., Leonor, C., Utenova, L., Zhang, G., AbdelBaqi, M., Malla, Y., Arshad, M., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2025.116819 · Cited by 7
Ding, L., Song, L., Han, Y., Wang, J., Lyu, Y., Song, M., Li, X., He, W., Chen, Q., Ding, P., et al. (2026) · Cell Host & Microbe · doi:10.1016/j.chom.2026.01.017 · Cited by 5
Oral Metagenomic Analysis Techniques
Chung, S.-K. (2019) · Journal of dental hygiene science · doi:10.17135/jdhs.2019.19.2.86 · Cited by 4
Zhu, J., Li, M., Li, J., & Wu, J. (2024) · Carbohydrate Research · doi:10.1016/j.carres.2024.109172 · Cited by 4
Microbial Biofilms and Pathobiology of Gingivitis and Periodontitis
Miller, D. P. (2025) · Springer series on biofilms · doi:10.1007/978-3-031-82202-5_10 · Cited by 4
Advances in Biotechnological Tools and Techniques for Metatranscriptomics
Singh, N., Vaishali, Bharti, M. K., Burman, V., & Sharma, V. (2021) · Springer eBooks · doi:10.1007/978-981-15-9758-9_27 · Cited by 1
Levine, M., & Lohinai, Z. M. (2021) · Vide Leaf, Hyderabad eBooks · doi:10.37247/pamed2ed.3.2021.22 · Cited by 4
Ebersole, J. L., Kirakodu, S. S., & Gonzalez, O. (2022) · Molecular Oral Microbiology · doi:10.1111/omi.12377 · Cited by 5
Hydrogen peroxide is a central determinant of oral polymicrobial synergy
Lamont, R. J. (2016) · Environmental Microbiology · doi:10.1111/1462-2920.13537 · Cited by 5
“…organisms can vary between individuals or even between disease sites in the same individual, indicating that it is the metagenome or metatranscriptome that represents the fundamental etiological unit, rather than the roster of bacteria per se (Jorth et al., 2014, DuranPinedo et al., 2011).”
BackgroundBACTERIAL BIOFILM CELLS QUANTIFICATION TECHNIQUES: WHERE IS CONSENSUS IN OVER TWO DECADES?
Olwal, C. O., Ochiel, D. O., Onyango, D. M., & Angienda, P. O. (2017) · Journal of Microbiology Biotechnology and Food Sciences · doi:10.15414/jmbfs.2017.7.2.168-173 · Cited by 4
“NGS technologies can identify specific bacterial biofilms in clinical (Huebinger et al., 2013) and environmental samples (Jorth et al., 2014).”
BackgroundWade, W. G. (2016) · Wiley eBooks · doi:10.1002/9781118982907.ch4 · Cited by 4
Tocarruncho, O. I., Neuta, Y., Lesmes, Y. A., Castillo, D. M., Leal, S., Chambrone, L., & Lafaurie, G. I. (2025) · Clinical Implant Dentistry and Related Research · doi:10.1111/cid.13423 · Cited by 3
The Dentin Microbiome: A Metatranscriptomic Evaluation of Caries-Associated Bacteria
de Oliveira, S. G., Jardim, R., Kotowski, N., Dávila, A. M. R., Filho, H. R. S., Ruiz, K. G. S., & Aguiar, F. H. B. (2025) · Biomedicines · doi:10.3390/biomedicines13030583 · Cited by 3
“This approach provides a snapshot of the transcriptional activity within the oral microbiome and highlights the specific genes and pathways that are differentially expressed under various conditions [16–18].”
Jang, E.-Y., Yang, S. B., Chun, J., Kwack, K. H., Kang, S. W., Lee, J., & Moon, J.-H. (2025) · Journal of Oral Microbiology · doi:10.1080/20002297.2025.2540827 · Cited by 3
“The spatial structure of biofilms and host-derived signals are thought to influence bacterial behavior and gene expression, potentially inducing heterogeneity even within clonal populations [20,21].”
Villhauer, A. L., Zhu, M., Shi, W., Xie, X. J., Hughes, P., Lesch, A., Weber‐Gasparoni, K., Kolker, J. L., Drake, D. R., & Banas, J. A. (2023) · Frontiers in Dental Medicine · doi:10.3389/fdmed.2023.991746 · Cited by 4
“Predictive modeling that includes microbiological factors has been explored through screening for speci fi c species and computer modeling based on oral microbiome sampling (22, 36, 38, 39).”
Jeong, K., Puth, S., Park, M. J., Lee, H., Kim, S. H., Rhee, J. H., & Lee, S. E. (2017) · International Journal of Oral Biology · doi:10.11620/ijob.2017.42.2.063 · Cited by 3
Dysbiosis of the Oral Microbiome
Ribeiro, A. A., & Arnold, R. R. (2019) · Springer eBooks · doi:10.1007/978-3-030-28737-5_8 · Cited by 3
Nature of Periodontal Diseases
Buduneli, N. (2019) · Springer eBooks · doi:10.1007/978-3-030-37317-7_2 · Cited by 4
Self-citationThe Oral Microbiome Bank of China
Peng, X., Zhou, X., Xu, X., Li, Y., Li, Y., Li, J., Su, X., Huang, S., Xu, J., & Liao, G. (2020) · Springer eBooks · doi:10.1007/978-981-15-7899-1_7 · Cited by 3
Metagenome-assembled microbial genomes (n = 3,448) of the oral microbiomes of Tibetan and Duroc pigs
Hu, H. W., Huang, Y., Yang, F., Ma, L., Zhang, J., Deng, X., Ma, N., Wang, K., Tao, Y., Lin, Q., et al. (2025) · Scientific Data · doi:10.1038/s41597-025-04413-1 · Cited by 3
Shaji, A., Ramachandran, A. K., Chandrasekaran, N., Karumaran, C. S., & Rabiathul Adhira, M. (2026) · Journal of Conservative Dentistry and Endodontics · doi:10.4103/jcde.jcde_963_25 · Cited by 2
“[25] This study has limitations.”
Subgingival biofilm microbiome in individuals with asthma and periodontitis: Metagenomic analysis.
Pinto, G. R., Carvalho, P. C., Carvalho, R. D. O., Conceição, R. R., Fortuna, V., Gomes-Filho, I., Trindade, S., & Sarmento, V. A. (2024) · Oral Diseases · doi:10.1111/odi.14913 · Cited by 2
Metadata
- Authors
- Jorth, P., Turner, K. H., Gumus, P., Nizam, N., Buduneli, N., & Whiteley, M.
- Affiliations
- The University of Texas at Austin (US)
- Department of Periodontology, School of Dentistry, Ege University, Izmir, Turkey
- Ege University (TR)
- Venue
- mBio
- Publisher
- American Society for Microbiology
- Published
- 2014-05
- Volume
- 5
- Issue
- 2
- Pages
- e01012-14
- ISSN
- 2150-7511 (ISSN-L)
- 2161-2129
- PMC
- PMC3977359
- OpenAlex
- W2146975236
- Cited by
- 386
- References
- 33
- Citations by year
- 2026: 18 · 2025: 30 · 2024: 24 · 2023: 13 · 2022: 25 · 2021: 33 · 2020: 45 · 2019: 39 · 2018: 33 · 2017: 40 · 2016: 33 · 2015: 39 · 2014: 14
- FWCI
- 56.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- mBio (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (5f31de021633-02)
- National Institute of Dental and Craniofacial Research (F31 DE021633, R01DE023193, 5F31DE021633-02, R01DE020100)
- Topics
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- oral microbiota, periodontitis, metatranscriptomics, microbial community metabolism, interpatient variability, periodontal plaque, virulence gene expression
- MeSH terms
- Adult, Female, Humans, Male, Mouth, Periodontitis, Metagenome, Transcriptome, Microbiota, Dysbiosis
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