the impact of microbiome research on oral health
TRANSCRIPT
THE IMPACT OF MICROBIOME RESEARCH ON ORAL HEALTH
DentaQuest Partnership & the Forsyth Institute Webinar
January 20, 2021
DOI: 10.35565/DQP.2021.3024
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Learning Objectives
1. Recognize that the human oral microbiome plays a critical role in human
health and disease
2. Understand that dysbiosis of microbiome could lead to disease, local and/or
systemic
3. Understand the remarkable diversity of oral microbiome, which goes beyond
simply bacteria
4. Understand the importance of achieving a holistic understanding of the oral
microbiome from an ecological perspective
• Xuesong (Song) He PhD. DDS.
• Forsyth Institute
• Forsyth-DentaQuest webinar
• 01/20/2021
•The Impact of Microbiome Research on Oral Health
• A Harvard School of Dental Medicine Affiliate
•䶚• Welch et.al PNAS
2016
• Gest. Notes Res.R. Soc.London
2004
• Clark. Brit J Exp Pathol 1924
• Kolenbrander et al MMBR 2002
• Griffen et al Plos One 2011
The origin of “Microbiome”
• Oral Microbiome: A mystic past
• Oral Microbiome: Revolutionized
• Oral Microbiome: Impact on disease
• Oral Microbiome: Beyond Bacteria
Outline
• Joshua
Lederberg
• "Ome Sweet'Omics--A Genealogical Treasury of Words". The Scientist. 2001
• The origin of “Microbiome”
• “It includes Lederberg's own recent coinage of microbiome, to
signify the ecological community of commensal, symbiotic, and
pathogenic microorganisms that literally share our body space
and have been all but ignored as determinants of health and
disease."
• Did Dr. Lederberg coin “Microbiome”?
• “A convenient ecological framework in which
to examine biocontrol systems is that of the
microbiome. This may be defined as a
characteristic microbial community
occupying a reasonably well-defined habitat
which has distinct physio-chemical
properties. This term thus not only refers to
the microorganisms involved but also
encompasses their theatre of activity.”
• --------Whipp, et al., 1988. Fungi in Biological Control
Systems. Manchester University Press.
• Sergei Nikolaievich Winogradsky (1856-1953), the Father of Microbial Ecology.
• Source: https://bit.ly/34PmZTX
• A Winogradsky Column showing the interconnected growth of coexisting microorganisms. Source: Mikrobiologie Praktikum Universität Kassel März 2007
• Whipp’s Microbiome concept and Winogradsky Column
• The origin of “Microbiome”
• Marchesi JR and Ravel J (2015) Microbiome, 3:31
• Microbiota
• The assemblage of microorganisms present in a defined environment.
• Microbiome
• The entire habitat, including the microorganisms (bacteria, archaea, lower and
higher eurkaryotes, and viruses), their genomes (i.e., genes), and the
surrounding environmental conditions.
• Metagenome
• The collection of genomes and genes from the members of a microbiota.
• The origin of “Microbiome”
• * The Legend of Worm
• 'The Tooth Worm as Hell’s
Demon’• 18th century ivory carving from France
•“䶚
• A Sumerian text from 5000 BC describes a “tooth worm”
• Oracle bone script in China 1500 BC
describing “tooth worm”
• Oral Microbiome: a mystic past
• “I didn’t clean my teeth for three days and then took the material that had lodged in
• small amounts on the gums above my front teeth. . . . I found a few living animalcules.”
• Antonie van Leeuwenhoek (1632–1723)
• * The Legend of Worm…continued..
• 1924 J. K.
Clarke
• Streptococcus mutans
• Aggregatibacter actinomycetemcomitans• Streptococcus spp.
• Actinobacillus spp.• Porphyromonas spp.
• Treponema spp.• …
• Oral Microbiome: a mystic past
• Multi-omics
analysis
• …..
• Kchouk et al Biology and Medicine 2017
• Next generation sequencing (NGS)
• Oral Microbiome: Revolutionized
• Dominguez –Bello et al. PNAS 2010
• Oral Microbiome: Revolutionized
• Sulyanto et al. Sci. Rep. 2019
• * Understanding establishment of oral microbiome
• Welch and Borisy et.al PNAS
2016
• Balachandran et al. JDR
2020
• Utter et al. Biorxiv 2020
• New techniques
• Spectrum
imaging
• Meta-
pangenome
• Targeted isolation and cultivation of uncultivated
bacteria
• by reverse genomics
• Oral Microbiome: Revolutionized
• The impact of microbiome research on understanding oral health
and disease
• Oral Microbiome: Impact on disease
• Oral infectious disease etiology--A major paradigm shift from the concept of “one-germ, one-disease”
to that of dysbiosis and polymicrobial diseases.
• Microbiome-based disease prediction, diagnosis and prognosis.
• Oral disease treatment—from non-discriminative killing to targeted microbial
modulation.
• Impact of oral microbiome research on Dental
Caries:
• Homo erectus (2 m) caries lesion
• Global Burden of Untreated Caries: Permanent teeth 2017
• Peres et al Lancet 2019
• Total dental expenditures : $140B in 2019
• Oral Microbiome: Impact on disease
• Dental Caries: A Multifactorial Disease
• Dr. Robert H. Selwitz
• Oral Microbiome: Impact on disease
• Questions:
1) How diverse are the caries microbial ecosystems?
2) Are they lesion site/tissue-specific?
3) Population specific?
4) What’s the functional structure of the caries
– microbial community?
• Simon-Soro et al Trends in
Microbiology
• Bacterial composition of different oral
samples from the same individual
• The bacterial composition of caries is
tissue dependent
• Extraordinarily diverse microbial ecosystems associated with dental caries
• Oral Microbiome: Impact on disease
• Cariogenic bacteria---beyond Streptococcus mutans:
• Streptococcus sobrinus
• Actinomyces spp.
• (Actinomyces naeslundii)
• Lactobacillus spp.
• (Lactobacillus fermentum)
• Bifidobacterium
spp.
• Scardovia
wiggsiae
• Streptococcus
mutans
• Oral Microbiome: Impact on disease
• Different metatranscriptomic profiles of caries lesions
• Simon-Soro et al Trends in Microbiology
• Oral Microbiome: Impact on disease
• Specific plaque hypothesis: (following Koch postulates) (Loesche 1975)
• Orland et al (1954). J Dent Res 33(2): 147-174.
• 1924 J. K. Clarke
• Streptococcus
mutans
• Ecological plaque hypothesis: (Kleinberg 2002, Marsh 2006).
• Change (Dysbiosis) of the Oral
Microbiota
• from Health to Disease (Caries)
• (Killian et al. 2016)
• Oral Microbiome: Impact on disease
• Teng et. al Cell Host&Microbe 2015
• Age-dependent microbiota development is perturbed by early childhood caries (ECC) onset
• Shifts in microbiota precede manifestation of clinical symptoms of ECC
• Microbial Indicators of Caries, when de-trended for age, can predict ECC onset
• Oral Microbiome: Impact on disease
> Treatment of caries as a microbial disease
• Baker et al. Front. Microbiol. 2019 • Yang et al. 2018 ACS Appl. Mater. Interfaces
• Oral Microbiome: Impact on disease
• Oral microbiome and systemic diseases
• Willis et al. Microorganisms 2020.
• Oral Microbiome: Impact on disease
• Diaz et al. Virulence 2017
• https://www.nature.com/articles/s41598-018-30705-1
• Mycobiome • Phagome
• Parasitic Nanosized
• Candidate Phyla Radiation (CPR)
• McLean et al. Cell Reports 2020
• Oral Microbiome: Beyond Bacteria
• Symbiotic Relationship between Streptococcus
mutans and Candida albicans Synergizes Virulence in vivo
• Falsetta et al. I&I 2014
• XH001
+LC001
• TMx/XH0
071
+LC001
• Oral Microbiome: Beyond Bacteria
• He et al. unpublished
• Association of parasitic TM7 protects bacterial host from
phage infection
• TM
7x
• Actinomyces
sp.
• XH001
• Oral Microbiome: Beyond Bacteria
• Achieve better understanding of oral microbiome from a holistic perspective
• Baker et al. Trends in Microbiology 2017
•Challenges in Oral Microbiome Study:
–1) Address fundamental questions relating to the principles governing the assembly,
dynamics, stability and vulnerability to disturbance of the oral microbiome;
–2) Achieve a holistic view of intra- and cross-kingdom interactions among members of
the oral microbiome, as well as microbial-host interaction;
–3) From “association” to “causation”;
–4) Cultivate yet-to-be cultivated oral bacterial species and study their role in health and
disease;
–5) Link between oral and systemic diseases;
–6) Search for novel/effective solutions for fighting dental caries and periodontal disease
Acknowledgements:
• All the research teams whose work has been cited in this talk;
• All those whose work has not been cited due to the time constraint.
Forsyth Symposium 2021 “Oral Microbiome: Beyond Bacteria”
Oct. 28-29, 2021
Forsyth Institute
Cambridge, Massachusetts
https://www.forsyth.org
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