Modulating the Microbiome Towards Health

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  1. Goal
  2. Background
  3. Gaps and Opportunities
  4. Specific Areas of Interest
  5. References

September 2024

Oral Microbiota and Bacterial Disease
Integrative Biology and Infectious Disease Branch 
Division of Extramural Research

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Goal

The goal for this initiative is to encourage focused efforts for development of microbiome directed therapies for oral disease. Building on studies of oral microbial ecology and gut microbiome therapies, the potential now exists to translate basic research into effective therapy. Dysbiosis of the oral microbiome is a core step in development of periodontitis, caries, and oral cancers [1]. Maintenance of a healthy oral microbiome involves a balancing act of retaining commensal, health-associated microbiota in order to restrain growth of opportunistic and acquired pathogens. Although various treatments for oral diseases exist, so far none have been based in direct modulation of the oral microbiome. Directly modulating the oral microbiome offers advantages such as reduced reliance on antimicrobials, longer lasting impact through establishment of health-related organisms and positive effects on systemic disease outside of the oral cavity.

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Background

Through numerous efforts, the oral microbiome is more well characterized than other microbiome sites, providing extensive data sets for starting points for modulation and targeting efforts [2-3]. Microbiome directed therapies generally fall into four categories: i) Diet and prebiotics that target expansion of specific organisms, ii) reconstitution with symbiotic bacterial consortia, iii) use of engineered microbiota such as those modified to produce substances or associate with specific targets, and iv) use of bioactive compounds derived from microbiota [4-5].

Fecal microbiome transplants revolutionized resolution of Clostridium difficile infections in the gut [6]. And modulation of the gut microbiome through diet, prebiotics, and probiotics has shown promise in improving GI and dementia-related disorders and cancer immunotherapies [7-9]. While microbiome manipulation therapies have been demonstrated effectively in the gut microbiome [4], none have yet been established for oral microbiome-related disease. Microbiome modulation has the potential to both help optimize disease resistance and cure disease [10]. The challenges to effectively use microbiome modulation as therapy include understanding the symbiotic members of the microbiota, the community response to diet and supplements, interspecies interactions within the community, and the impact of any changes on the host. Use of such a therapy also comes with concerns about pathogen transmission as well as defining the characteristics of any new community provided or created. Targeting microbiota dysbiosis through direct therapeutic options represents a huge challenge, but one that also presents enormous opportunities.

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Gaps and Opportunities

Projects investigating oral microbial ecology, biogeography, spatial structure, and interspecies interactions within the oral microbiome have provided a wealth of data. However, this data has not yet led to focused microbiome-targeted therapies. This initiative encourages movement beyond the data to functional purposes, focusing on the projects needed to engineer the oral microbiome toward health. Opportunities exist within the following areas:

  • Understanding how symbiotic microbiota support, tolerate, or reject each other within the community environment and select those best fit for therapeutic use.
  • Determining the role of a microbiota-directed complementary diet.
  • Investigating bacteriophage that can target and clear pathogenic bacterial species.
  • Developing methods to improve colonization resistance and community stability.
  • Developing computational approaches to predict, analyze, and monitor health and dysbiosis of a microbial community.
  • Developing small molecules targeting or blocking essential pathogen colonization, invasion, and/or metabolic functions.
  • Improving production and delivery of microbiota-derived mediators.
  • Integrating omics-based approaches, particularly metaproteomics and metabolomics, to examine how oral communities change functionally and taxonomically over time to target appropriate community composition and development for modulation therapy.
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Specific Areas of Interest

  • Models for assessment of the mechanisms driving the community from dysbiosis to health.
  • Targeted pathogen elimination therapies.
  • Commensal driven modulation strategies.
  • Targeted therapies affecting oral homeostasis.
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References

  1. Radaic A, Kapila YL. The oralome and its dysbiosis: New insights into oral microbiome – host interactions. Comput Struct Biotechnol J. 2021 Feb 27;19:1335-1360. doi: 10.1016/j.csbj.2021.02.010.
  2. Bik EM, Long CD, Armitage GC, Loomer P, Emerson J, Mongodin EF, et al. Bacterial diversity in the oral cavity of 10 healthy individuals. ISME J. 2010 Aug;4(8):962-974. Epub 2010 Mar 25. doi: 10.1038/ismej.2010.30.
  3. Nearing JT, DeClercq V, Van Limbergen J, Langille MGI. Assessing the variation within the oral microbiome of healthy adults. mSphere. 2020 Sep 30;5(5):e00451-20. doi: 10.1128/mSphere.00451-20.
  4. Gowen R, Gamal A, Di Martino L, McCormick TS, Ghannoum MA. Modulating the microbiome for Crohn’s disease treatment. Gastroenterology. 2023 Apr;164(5):828-840. Epub 2023 Jan. doi: 10.1053/j.gastro.2023.01.017.
  5. Gebrayel P, Nicco C, Al Khodor S, Bilinski J, Caselli E, Comelli EM, et al. Microbiota medicine: Towards clinical revolution. J Transl Med. 2022 Mar 7;20(1):111. doi: 10.1186/s12967-022-03296-9.
  6. Hui W, Li T, Liu W, Zhou C, Gao F. Fecal microbiota transplantation for treatment of recurrent C. difficile infection: An updated randomized controlled trial meta-analysis. PLoS One. 2019 Jan 23;14(1):e0210016. doi: 10.1371/journal.pone.0210016.
  7. Meng HYH, Mak CCH, Mak WY, Zuo T, Ko H, Chan FKL.Probiotic supplementation demonstrates therapeutic potential in treating gut dysbiosis and improving neurocognitive function in age-related dementia. Eur J Nutr. 2022 Jun;61(4):1701–1734. Epub 2022 Jan 10. doi: 10.1007/s00394-021-02760-4.
  8. Fernandes MR, Aggarwal P, Costa RGF, Cole AM, Trinchieri G.Targeting the gut microbiota for cancer therapy. Nat Rev Cancer. 2022 Dec;22(12):703-722. Epub 2022 Oct 17. doi: 10.1038/s41568-022-00513-x.
  9. Sorbara MT, Pamer EG. Microbiome-based therapeutics. Nat Rev Microbiol.2022 Jun;20(6):365-380. Epub 2022 Jan 6. doi: 10.1038/s41579-021-00667-9.
  10. Zhang Y, Wang X, Li H, Ni C, Du Z, Yan F. Human oral microbiota and its modulation for oral health. Biomed Pharmacother. 2018 Mar;99:883-893. Epub 2018 Feb 20. doi: 10.1016/j.biopha.2018.01.146.
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Last Reviewed
September 2024