THE IMPACT OF MICROBIOME RESEARCH ON ORAL HEALTH

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

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Presenters

• 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


https://bit.ly/34PmZTX


• “Microbiome” and “Microbiota”

• 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 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)


• Human Oral Microbiome

Database

• Human Microbiome Project


• Dominguez –Bello et al. PNAS 2010


• 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


• The impact of microbiome research on understanding oral health

and 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


• Dental Caries: A Multifactorial Disease

• Dr. Robert H. Selwitz


• 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


• Cariogenic bacteria---beyond Streptococcus mutans:

• Streptococcus sobrinus

• Actinomyces spp.

• (Actinomyces naeslundii)

• Lactobacillus spp.

• (Lactobacillus fermentum)

• Bifidobacterium

spp.

• Scardovia

wiggsiae

• Streptococcus

mutans


• Different metatranscriptomic profiles of caries lesions

• Simon-Soro et al Trends in Microbiology


• 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)


• 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


> Treatment of caries as a microbial disease

• Baker et al. Front. Microbiol. 2019 • Yang et al. 2018 ACS Appl. Mater. Interfaces


• Oral microbiome and systemic diseases

• Willis et al. Microorganisms 2020.


• 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


• Symbiotic Relationship between Streptococcus

mutans and Candida albicans Synergizes Virulence in vivo

• Falsetta et al. I&I 2014

• XH001

+LC001

• TMx/XH0

071

+LC001


• He et al. unpublished

• Association of parasitic TM7 protects bacterial host from

phage infection

• TM

7x

• Actinomyces

sp.

• XH001


• 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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THE IMPACT OF MICROBIOME RESEARCH ON ORAL HEALTH