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.
“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]
Application of transcriptomic approaches has proved extremely significant for delineating both microbial and host gene expression in the context of oral health and pathology.
“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]
Despite dissimilar phylogeny, functional signatures among the oral microbiota are often conserved from one individual to another.
“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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Microbiota and Metatranscriptome Changes Accompanying the Onset of Gingivitis
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Metatranscriptome of the Oral Microbiome in Health and Disease
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“As a next step, metatranscriptomics (52, 53) or other specialized analyses can then be applied to a smaller number of representative samples.”
BackgroundHoggard, M., Mackenzie, B. W., Jain, R., Taylor, M. W., Biswas, K., & Douglas, R. G. (2016) · Clinical Microbiology Reviews · doi:10.1128/cmr.00060-16 · Cited by 118 · see citing works
“In one study, the application of metatranscriptomics to periodontal disease identified conserved changes in microbial community metabolism associated with this disease, against a background of high interpatient variability in community composition (205).”
BackgroundDiversification of Type VI Secretion System Toxins Reveals Ancient Antagonism among Bee Gut Microbes
Steele, M. I., Kwong, W. K., Whiteley, M., & Moran, N. A. (2017) · mBio · doi:10.1128/mbio.01630-17 · Cited by 118 · see citing works
“For experiment B, DNA and RNA were extracted using the bead-beating and RNA-Bee method described by Jorth et al. (51).”
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Prediction of Periodontal Inflammation via Metabolic Profiling of Saliva
Kuboniwa, M., Sakanaka, A., Hashino, E., Bamba, T., Fukusaki, E., & Amano, A. (2016) · Journal of Dental Research · doi:10.1177/0022034516661142 · Cited by 110 · see citing works
“A recent metatranscriptomics study that utilized subgingival plaque samples identified enhanced expression of genes associated with histidine degradation as a conserved metabolic shift during development of periodontal disease (Jorth et al. 2014).”
BackgroundAdvancements toward a systems level understanding of the human oral microbiome
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Understanding human health through metatranscriptomics
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Dysbiotic Biofilms Deregulate the Periodontal Inflammatory Response
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Transcriptome analysis in whole blood reveals increased microbial diversity in schizophrenia
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Dual Transcriptomic Profiling of Host and Microbiota during Health and Disease in Pediatric Asthma
Pérez‐Losada, M., Castro‐Nallar, E., Bendall, M. L., Freishtat, R. J., & Crandall, K. A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0131819 · Cited by 104 · see citing works
“microbiota [16–18, 20, 22, 63].”
BackgroundEnvironmental filtering increases with elevation for the assembly of gut microbiota in wild pikas
Li, H., Zhou, R., Zhu, J., Huang, X., & Qu, J. (2019) · Microbial Biotechnology · doi:10.1111/1751-7915.13450 · Cited by 102 · see citing works
“Since some species in this genus have been reported to be involved in pyruvate metabolism in humans (Jorth et al., 2014), we speculate they play important roles in the gut niche of high-altitude pikas.”
BackgroundIntrinsic Antimicrobial Resistance Determinants in the Superbug Pseudomonas aeruginosa
Murray, J. L., Kwon, T., Marcotte, E. M., & Whiteley, M. (2015) · mBio · doi:10.1128/mbio.01603-15 · Cited by 100 · see citing works
Self-citationPeriodontal inflammation: Integrating genes and dysbiosis
Zhang, S., Yu, N., & Arce, R. M. (2019) · Periodontology 2000 · doi:10.1111/prd.12267 · Cited by 101 · see citing works
Porphyromonas gingivalis: Immune Subversion Activities and Role in Periodontal Dysbiosis
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Capturing the genetic makeup of the active microbiome in situ
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Guerrero-Preston, R. E., White, J. R., Godoy‐Vitorino, F., Rodríguez-Hilario, A., Navarro, K., González, H., Michailidi, C., Jedlicka, A., Canapp, S., Bondy, J., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.20677 · Cited by 98 · see citing works
“Some studies have observed that Fusobacterium nucleatum upregulates the expression of lysine degradation pathway leading to butyrate production in periodontitis patients [87].”
Armed to the Teeth—The Oral Mucosa Immunity System and Microbiota
Ptasiewicz, M., Grywalska, E., Mertowska, P., Korona‐Głowniak, I., Poniewierska-Baran, A., Niedźwiedzka‐Rystwej, P., & Chałas, R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23020882 · Cited by 102 · see citing works
Fungal-bacterial interactions and their relevance to oral health: linking the clinic and the bench
Diaz, P. I., Strausbaugh, L. D., & Dongari‐Bagtzoglou, A. I. (2014) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2014.00101 · Cited by 97 · see citing works
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“…lack of animal-based replication for the metatranscriptomic data does potentially limit the ability to generalize our results, this approach has been successfully utilized by numerous groups in the past to accurately characterize transcriptional activity across communities of bacteria (19, 31–33).”
Short-Chain Fatty Acid and FFAR2 Activation – A New Option for Treating Infections?
Schlatterer, K., Peschel, A., & Kretschmer, D. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.785833 · Cited by 93 · see citing works
Oral fungal-bacterial biofilm models in vitro: a review
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Unravelling interspecies interactions across heterogeneities in complex biofilm communities
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“nucleatum is a key contributor to butyrate production (Jorth et al., 2014), which has been linked to the development of periodontal disease (Niederman, Buyle- Bodin, Lu, Robinson, & Naleway, 1997).”
BackgroundSakanaka, A., Kuboniwa, M., Hashino, E., Bamba, T., Fukusaki, E., & Amano, A. (2017) · Scientific Reports · doi:10.1038/srep42818 · Cited by 90 · see citing works
Impact of systemic factors in shaping the periodontal microbiome
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The human microbiome encodes resistance to the antidiabetic drug acarbose
Balaich, J. N., Estrella, M. A., Wu, G. G., Jeffrey, P. D., Biswas, A. G., Zhao, L., Korennykh, A. V., & Donia, M. S. (2021) · Nature · doi:10.1038/s41586-021-04091-0 · Cited by 84 · see citing works
Mucosal Microbiome in Patients with Recurrent Aphthous Stomatitis
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“Metagenomic studies of the oral microbiome in RAS patients, as recently reported for healthy individuals ( Jorth et al. 2014), will define conserved changes in metabolic and virulence gene expression of bacterial communities associated with RAS.”
BackgroundEdlund, A., Yang, Y., Yooseph, S., Hall, A. P., Nguyen, D. D., Dorrestein, P. C., Nelson, K. E., He, X., Lux, R., Shi, W., et al. (2015) · The ISME Journal · doi:10.1038/ismej.2015.72 · Cited by 84 · see citing works
“…sequencing of mRNA, expression profiles have been generated representing snapshots of the activity within in vivo oral bacterial communities from individual subjects representing healthy and diseased groups (Frias-Lopez and DuranPinedo, 2012; Jorth et al., 2014; Benítez-Páez et al., 2014).”
BackgroundThe enduring importance of animal modelsin understanding periodontal disease
Hajishengallis, G., Lamont, R. J., & Graves, D. T. (2015) · Virulence · doi:10.4161/21505594.2014.990806 · Cited by 84 · see citing works
“This notion is supported by a recent metatranscriptomic study which showed that disease-associated microbial communities exhibit conserved metabolic and virulence gene expression profiles, despite high inter-patient variability in terms of microbial composition.(26) Therefore, a conserved periodontitis-associated micr…”
ResultDysbiosis From a Microbial and Host Perspective Relative to Oral Health and Disease
Cugini, C., Ramasubbu, N., Tsiagbe, V. K., & Fine, D. H. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.617485 · Cited by 86 · see citing works
Shiba, T., Watanabe, T., Kachi, H., Koyanagi, T., Maruyama, N., Murase, K., Takeuchi, Y., Maruyama, F., Izumi, Y., & Nakagawa, I. (2016) · Scientific Reports · doi:10.1038/srep30997 · Cited by 83 · see citing works
“Functional pathways in healthy and periodontitis sites have been compared by metatranscriptomic analysis 43 .”
Manor, O., Levy, R., & Borenstein, E. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.07.021 · Cited by 80 · see citing works
“Other studies used meta-transcriptome derived networks to identify pathways not previously associated with periodontal disease (Jorth et al., 2014) or alternative pathways to biomass production (Xiong et al., 2012).”
The Oral Mouse Microbiome Promotes Tumorigenesis in Oral Squamous Cell Carcinoma
Stashenko, P., Yost, S. C., Choi, Y., Danciu, T., Chen, T., Yoganathan, S., Kressirer, C. A., Ruiz-Tourrella, M., Das, B., Kokaras, A. S., et al. (2019) · mSystems · doi:10.1128/msystems.00323-19 · Cited by 80 · see citing works
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“Typically, increased microbial diversity has been documented in the majority of studies of periodontitis [13,14,9], but recently a study of metatranscriptomics in periodontitis has reported decreased richness and diversity in diseased sites [29].”
Ecological Therapeutic Opportunities for Oral Diseases
Hoare, A., Marsh, P. D., & Diaz, P. I. (2017) · Microbiology Spectrum · doi:10.1128/microbiolspec.bad-0006-2016 · Cited by 81 · see citing works
“Such metabolic models may allow prediction of the role that each species may have in the health- and/or disease-associated consortia (5, 276, 277, 278).”
BackgroundEnvironmental factors and periodontal microbiome
Buduneli, N. (2020) · Periodontology 2000 · doi:10.1111/prd.12355 · Cited by 80 · see citing works
Self-citationHigh-resolution characterization of the human microbiome
Noecker, C. A., McNally, C. P., Eng, A., & Borenstein, E. (2016) · Translational research · doi:10.1016/j.trsl.2016.07.012 · Cited by 77 · see citing works
Detection, treatment and prevention of endodontic biofilm infections: what’s new in 2020?
Abusrewil, S., Alshanta, O. A., Albashaireh, K. Z., Alqahtani, S. S., Nile, C. J., Scott, J. A., & McLean, W. (2020) · Critical Reviews in Microbiology · doi:10.1080/1040841x.2020.1739622 · Cited by 77 · see citing works
“These changes are not conserved among patients, with inter-individual microbiome variability resulting in similar patient symptoms (Jorth et al. 2014).”
BackgroundAsgari, E., Garakani, K., McHardy, A. C., & Mofrad, M. R. K. (2018) · Bioinformatics · doi:10.1093/bioinformatics/bty296 · Cited by 82 · see citing works
“Consequently, dysbiosis of the human microbiome can promote several diseases, including asthma [2, 3], irritable bowel syndrome [4, 5], Clostridium difficile infection [6], chronic periodontitis [7, 8], cutaneous leishmaniasis [9], obesity [10, 11], chronic kidney disease [12], Ulcerative colitis [13], and Crohns dise…”
Transcriptome analysis of bacteriophage communities in periodontal health and disease
Santiago-Rodríguez, T. M., Naidu, M., Abeles, S. R., Boehm, T. K., Ly, M., & Pride, D. T. (2015) · BMC Genomics · doi:10.1186/s12864-015-1781-0 · Cited by 75 · see citing works
“Despite the lack of studies characterizing oral phage gene expression, there have been efforts to characterize their bacterial counterparts [29, 38] and to associate patterns of transcription with disease severity [39].”
BackgroundCorrêa, R. O., Vieira, A. T., Sernaglia, E. M., Lancellotti, M., Vieira, A. T., Ávila-Campos, M. J., Rodrigues, H. G., & Vinolo, M. A. R. (2017) · Cellular Microbiology · doi:10.1111/cmi.12720 · Cited by 75 · see citing works
Is there an association between obstructive sleep apnea syndrome and periodontal inflammation?
Nizam, N., Başoğlu, Ö. K., Taşbakan, M. S., Lappin, D. F., & Buduneli, N. (2015) · Clinical Oral Investigations · doi:10.1007/s00784-015-1544-y · Cited by 74 · see citing works
Self-citationBiosensor and Lab-on-a-chip Biomarker-identifying Technologies for Oral and Periodontal Diseases
Steigmann, L., Maekawa, S., Sima, C., Travan, S., Wang, C.-W., & Giannobile, W. V. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.588480 · Cited by 77 · see citing works
- 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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