The Functional Oral Microbiome

Goal

The goal of this initiative is to encourage multi-dimensional and nuanced research that explores the interconnectedness and uniqueness of the oral microbiome community. This initiative will encourage studies beyond the bacteriome to explore interkingdom microbial interactions and complex community systems and networks in a physiologically relevant setting to understand the role of community interactions in the maintenance of health and in driving transition to dysbiosis and disease in the oral cavity.

Background

To date, most microbiome studies focus on the bacteriome, despite the fact that the term "microbiome" refers to all microorganisms^1-3. The oral microbiome is comprised of a multitude of organisms, including bacteria, fungi, viruses, archaea and protozoa, which can all serve an essential role in oral and systemic health. The identification of individual species within this community with roles in maintenance of good oral health and in the shift to dysbiosis and disease has been and continues to be well documented. Despite a wealth of knowledge regarding specific species present, much remains unclear regarding the mechanisms driving the stability, persistence, and resistance of the oral microbial community as a whole. To better understand the physiologic and metabolic interspecies and interkingdom interactions responsible for the function of the oral microbiome, hypotheses such as the ecological plaque and the polymicrobial synergy and dysbiosis hypotheses have been constructed and examined^4-6. From these concepts, the more nuanced idea that multispecies communities contribute collectively rather than individually to development of dysbiosis or maintenance of a healthy community has begun to be examined^7-9. Interactions between interkingdom microbial communities are heterogeneous and complex, requiring foundational research to understand and potentially control, manipulate, and optimize these interactions for beneﬁcial applications.

Building on current studies, the field is positioned to expand from investigations of single or dual species systems to complex, interspecies and interkingdom relationships. A new focus on complex systems level analysis will provide a shift from compositional to functional studies. This initiative synergizes with two recent efforts begun through the NIH Common Fund’s Nutrition of Precision Health program as well as a recent NIDDK FOA (PAR-21-253) focused on microbial metabolites from the microbiome. Studies increasing our understanding of oral microbiota dynamics, including interkingdom interactions in the oral ecosystem, are needed to unravel the complexities of the human oral microbiome in healthy dental and oral tissues and explore the functional and metabolic alterations associated with diseased states. Understanding these complexities is essential for future research in the involvement of the oral microbiome in systemic health and disease as well as for the potential development of oral microbiome transplants.

Gaps and Opportunities

This initiative covers research topics of high priority to NIDCR in the area of oral microbiome research, spanning the spectrum from basic to translational sciences. It is anticipated that a Funding Opportunity Announcement and/or Notice of Special Interest would be released focused on areas of interest that include:

Integration of -omics approaches in understanding interspecies and interkingdom interactions.
Examination of colonization resistance, community stability, and persistence in complex community systems.
Assessment of the role of spatial structure, including the biofilm matrix, in community function.
Assessment of the emergent properties of the oral microbiome driven by interkingdom/species connections and communications; assessing functional signatures and molecular dialogue in multi-species environments.
Examination of the role of microbial metabolism modulation in cooperative metabolism, nutritional interrelationships, species specialization and interactions promoting growth and fitness.
Establishment and analysis of metabolic interactions models – particularly in the area of uncultivable organism relationships and for assessment of network targets for therapeutic and preventative approaches.
Development of ex vivo synthetic biofilm systems supporting community analysis and potential future efforts toward oral microbiome transplants.

Through all research opportunities, a focus inclusive of data management and maintenance is essential and involvement of a computational biologist will be encouraged.

Impact

There has been an important shift in the understanding of the role of individual species to a more nuanced view of the role of the whole microbial community in maintenance and regulation of health and disease within the oral environment. While we recognize that the microbiome can significantly impact health and disease, how it does so is not yet clear. This initiative aligns with that recognition and the need for better understanding of community ecology and interactions forming a basis for development in new therapies and prevention. With the advancement in understanding of the different species in the community, models using three or more species, and the advanced metagenomic, metatranscriptomic, and metabolomic tools now available, the capacity now exists to develop approaches to study complex communities and functional interactions^10-11.

Current Portfolio

While the NIDCR funds numerous studies on the oral microbiome, there is a lack of projects focused on interkingdom microbial interactions and complex community systems and networks. The majority of funded oral microbiome studies focus on the oral bacteriome. Understanding how microbes change their virulence as a result of established and/or developing interactions is clinically relevant and could lead to new effective therapeutic strategies.

References

Lamont RJ, Koo H, Hajishengallis G. The oral microbiota: dynamic communities and host interactions. Nat Rev Microbiol. 16, 745-759 (2018)
Kleinstein SE, et al. Inflammatory Networks Linking Oral Microbiome with Systemic Health and Disease. J Dent Res. 99, 1131-1139 (2020).
Wan SX, et al. Cross-Kingdom Cell-to-Cell Interactions in Cariogenic Biofilm Initiation. Journal of Dental Research. 100, 74-81 (2021).
Marsh PD. Are dental diseases examples of ecological catastrophes? Microbiology. 149, 279–294 (2003).
Hajishengallis G, Lamont RJ. Beyond the red complex and into more complexity: the polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology. Mol. Oral Microbiol. 27, 409–419 (2012).
Ponde NO, et al. Candida albicans biofilms and polymicrobial interactions. Crit Rev Microbiol. 47, 91-111 (2021).
Hajishengallis G, Lamont RJ. Dancing with the stars: how choreographed bacterial interactions dictate nososymbiocity and give rise to keystone pathogens, accessory pathogens, and pathobionts. Trends Microbiol. 24, 477–489 (2016).
Stacy A, McNally L, Darch SE, Brown SP, Whiteley M. The biogeography of polymicrobial infection. Nat. Rev. Microbiol. 14, 93–105 (2016).
Diaz PI, and Valm AM. Microbial Interactions in Oral Communities Mediate Emergent Biofilm Properties. Journal of Dental Research. 99, 18-25 (2020).
Zemouri C, Ofiteru ID, Jakubovis NS. Future directions for studying resilience of the oral ecosystem. Br Dent J. 229, 769-773 (2020).
Duran‐Pinedo AE. Metatranscriptomic analyses of the oral microbiome. Periodontology. 2000 85, 28-45 (2021).

Last Reviewed
December 2024