1. Exploring the Oral
Microbial Ecosystem

2. Dr. Bonnie Feldman, DDS, MBA
As Your Autoimmunity Connection, we
consult with startup companies and
entrepreneurs who are producing new
products and services that will improve
research, diagnosis, and treatment for
autoimmunity.
DrBonnie360’s mission is to create a
digitally connected world of personalized
care for autoimmune patients.
drbonnie360.com
drbonnie360@gmail.com
http://bit.ly/2iKVEQj
@DrBonnie360
linkedin.com/in/bonniefeldman
(310)666-5312
Content & Visual Design by: Hailey Motooka

3. Marsh, Philip D. “Ecological Events in Oral Health and Disease: New Opportunities
for Prevention and Disease Control?” CDA Journal, vol. 45, no. 10, Oct. 2017.
Changes to the oral environment
drive deleterious shifts in the
microbiome (dysbiosis).
Prevention of oral diseases such
as dental caries and periodontal
disease depend not only on
biofilm control, but also
eliminating drivers of dysbiosis.
Host-microbe
interactions perturbed
Oral disease
Systemic disease
Bad diet
Poor plaque control
Low saliva flow
Altered host defense
Lifestyle risk factors
Broad spectrum antibiotics
Dysbiosis

4. Egija Zaura et al. “Acquiring and maintaining a normal oral microbiome: Current perspective,” Frontiers in
Cellular and Infection Microbiology (2014): 85. https://. www.ncbi.nlm.nih.gov/pmc/articles/PMC4071637/
Biological properties that confer stability in the microbiome are important for the prevention of
dysbiosis— a microbial shift towards disease. Oral health reflects the ability of the oral
ecosystem to adapt to and counteract perturbing stresses. Here the oral ecosystem is defined as
the oral microbiota, the saliva and host (mucosal) immunity.
The oral cavity harbors approximately 700 different, mostly anaerobic species. This study
investigated the effects of intimate kissing on the oral microbiota of 21 couples. In controlled
experiments of bacterial transfer, researchers determined there was an average total bacterial
transfer of 80 million bacteria per intimate kiss of 10 seconds.
Kort, Remco, et al. “Shaping the Oral Microbiota through Intimate Kissing.” Microbiome
vol. 2, no. 1, 2014, p. 41., doi:10.1186/2049-2618-2-41.

5. Devine, Deirdre A. et al. "Modulation of host responses by oral commensal bacteria.”
Journal of oral microbiology 7 (2015). <http://www.journaloforalmicrobiology.net/>
Immunomodulatory commensal bacteria are proposed to be essential for maintaining healthy
tissues, including priming immune responses to ensure rapid and efficient defenses against
pathogens. The default state of oral tissues is one of inflammation, which may be balanced by
regulatory mechanisms and anti-inflammatory resident bacteria.
Bacteria within the oral cavity play an integral role in biofilm formation. The formation of
biofilm in the form of plaque is a complex and rapidly evolving process involving several stages
of development. Bacteria first bind irreversibly to solid surfaces. Once bound, they mature,
disperse, and are able to colonize new habitats within the mouth.
Krzyściak, Wirginia et al. "The Role of Human Oral Microbiome in Dental Biofilm Formation.” InTech.
N.p., n.d. Web. <http://www.intechopen.com/books/microbial-biofilms-importance-and-
applications/the-role-of-human-oral-microbiome-in-dental-biofilm-formation>

6. The Biomes
of the
Oral Cavity
TONGUE
TEETH
SALIVA
GUMS
EAR, NOSE,THROAT

7. Hall, Michael W., et al. “Inter-Personal Diversity and Temporal Dynamics of Dental,Tongue, and
Salivary Microbiota in the Healthy Oral Cavity.” Npj Biofilms and Microbiomes, vol. 3, no. 1, 2017,
doi:10.1038/s41522-016-0011-0.
Oral bacterial communities that
inhabit supragingival plaque and
saliva are clearly distinct from one
another. The difference in biological
and physical properties of the tongue
dorsum and supragingival surface
reflects the distinctiveness of the
corresponding microbial
communities.

8. Sun, Beili, et al. “Evaluation of the Bacterial Diversity in the Human Tongue Coating Based on
Genus-Specific Primers for16S RRNA Sequencing.” BioMed Research International, vol. 2017,
2017, pp.1–12., doi:10.1155/2017/8184160.
The characteristics of tongue coating are potential determinants for disease diagnosis in
traditional Chinese medicine (TCM). Through 16 rRna sequencing, results indicated that the
richness of the bacterial communities in the patients with thin tongue coating and healthy
controls was higher than in patients with thick tongue coating.

9. Costalonga, Massimo, and Mark C. Herzberg. “The Oral Microbiome and the
Immunobiology of Periodontal Disease and Caries.” Immunology Letters, vol. 162, no. 2,
2014, pp. 22–38., doi:10.1016/j.imlet.2014.08.017.
Microbial communities of the tooth
surface and irregularities in the
enamel differ depending on diversity
and richness. Surfaces and sites with
highest diversity and richness within
ecological niches are most
susceptible to caries. When caries are
established, this acid environment
reduces the diversity and richness of
the local microbiota.

10. Struzycka, Izabela. “The Oral Microbiome in Dental Caries.” Polish Journal of
Microbiology, vol. 63, no. 2, Feb. 2014, pp. 127–135.
Caries develop as a result of an ecological imbalance in the stable oral microbiome.
Oral microorganisms form dental plaque on the surfaces of teeth, which is the cause of the
caries process, showing features of the classic biofilm.
Nasry, Bishoy, et al. “Diversity of the Oral Microbiome and Dental Health and Disease.” International
Journal of Clinical & Medical Microbiology, vol. 1, no. 2, 2016, doi:10.15344/2456-4028/2016/108.
During conditions of health or disease, the oral environment experiences cycles of
demineralization and remineralization that occurs on tooth surfaces. When the mineralization
equilibrium shifts to a net loss of hydroxyapatite, tooth decay occurs.

11. Zaura, Egija et al. "On the ecosystemic network of saliva in healthy young adults." The
ISME Journal (2017). <http://www.nature. com/ismej/journal/vaop/ncurrent/
full/ismej2016199a.html>.
The saliva ecosystem is composed
mainly of the salivary microbiome,
salivary metabolome, and host
related biochemical salivary
parameters. An over-specialization
toward either a proteolytic or a
saccharolytic ecotype may indicate
a shift toward a dysbiotic state.

12. Glurich, Ingrid et al. “Progress in Oral Personalized Medicine: Contribution of ‘omics.’” Journal of
Oral Microbiology 7.0 (2015): 28223. <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4561229/>.
Recent advances in genomics and related ‘omics’ are providing evolving understanding of oral
personalized medicine. Functional gene signatures detected in caries-associated saliva
microbiome profiles have been associated with systemic disease, suggesting that these profiles
can also help to predict diseases as well.
Yang, Fang et al. “Characterization of Saliva Microbiota’s Functional Feature Based on Metagenomic
Sequencing.” SpringerPlus 5.1 (2016): 2098. PMC. Web. 18 Jan. 2017.
<http://link.springer.com/article/10.1186/s40064-016-3728-6>.
Research suggests organismal structure of saliva microbiota is correlated with disease states
such as caries, gingivitis, and periodontal disease. Thus, organismal structure of saliva
microbiota can potentially serve as a proxy for the oral health of the host through site-specific
signatures and functional profiles of the saliva microbiota.

13. Lof, Marlos, et al. “Metabolic Interactions between Bacteria and Fungi in Commensal Oral
Biofilms.” Journal of Fungi, vol. 3, no. 3, 2017, p. 40., doi:10.3390/jof3030040.
The oral microbial interactome is not complete without detailed information about the fungi in
the oral cavity. Fungi have often only been studied in relation to disease, which gives an overall
wrong impression about these microorganisms. Therefore, the beneficial role of fungi may have
been overlooked.
• Kolenbrander, Paul E., et al. “Oral Multispecies Biofilm Development and the Key Role of Cell–
Cell Distance.” Nature Reviews Microbiology, vol. 8, no. 7, Jan. 2010, pp. 471–480.,
doi:10.1038/nrmicro2381.
Oral bacteria evolved to form biofilms on hard tooth surfaces and on soft epithelial tissues, which often
contain multiple bacterial species. Factors involved in the formation of these biofilms include the initial
adherence to the oral tissues and teeth, cooperation between bacterial species in the biofilm, the role
of signaling between the bacteria in pathogenesis, and the transfer of DNA between bacteria.

14. Liu, Bo, et al. “Deep Sequencing of the Oral Microbiome Reveals
Signatures of Periodontal Disease.” PLOS ONE, vol. 7, no. 6,Apr. 2012,
doi:10.1371/journal.pone.
A proliferation of pathogenic
bacteria within the mouth gives rise
to periodontitis, an inflammatory
disease known to also constitute a
risk factor for cardiovascular
disease. We reveal the diseased
microbiome to be enriched in
virulence factors, and adapted to a
parasitic lifestyle that takes
advantage of the disrupted host
homeostasis.

15. Schwarzberg, Karen, et al. “The Personal Human Oral Microbiome Obscures the Effects of Treatment
on Periodontal Disease.” PLoS ONE, vol. 9, no. 1, 2014, doi:10.1371/journal.pone.0086708.
Recent Next-Generation Sequencing (NGS) studies of the microbial diversity associated with periodontitis have
revealed strong, community-level differences in bacterial assemblages associated with healthy or diseased
periodontal sites. Deeper phylogenetic analysis of periodontal pathogen-containing
genera Prevotella and Fusobacterium found both unexpected diversity and differential treatment response
among species.
Yost, Susan, et al. “Potassium Is a Key Signal in Host-Microbiome Dysbiosis in Periodontitis.” PLOS
Pathogens, vol. 13, no. 6, 2017, doi:10.1371/journal.ppat.1006457.
Periodontitis is a polymicrobial inflammatory disease that affects a large proportion of the world's
population and has been associated with a wide variety of systemic health conditions, such as diabetes
and both cardiovascular and respiratory diseases. Levels of potassium in the periodontal pocket could
be an important element in of dysbiosis in the oral microbiome.

16. Hajishengallis, George. “Periodontitis: from Microbial Immune Subversion to Systemic
Inflammation.” Nature Reviews Immunology, vol. 15, no. 1, 2015, pp. 30–44., doi:10.1038/nri3785.
The transition from periodontal health to disease is associated with a dramatic shift from a symbiotic
microbial community to a dysbiotic microbial community composed mainly of anaerobic genera.
Persistence of dysbiotic oral microbial communities can mediate inflammatory pathology at local as
well as distant sites outside of the oral cavity.
Hajishengallis, George. “Immunomicrobial Pathogenesis of Periodontitis: Keystones, Pathobionts, and
Host Response.” Trends in Immunology, vol. 35, no. 1, 2014, pp. 3–11., doi:10.1016/j.it.2013.09.001.
Dysbiotic microbial communities of keystone pathogens and pathobionts are thought to exhibit
synergistic virulence whereby not only can they endure the host response but can also thrive by
exploiting tissue-destructive inflammation. This fuels a self-feeding cycle of escalating dysbiosis
and inflammatory bone loss, potentially leading to tooth loss and systemic complications.

17. Proctor, Diana M., and David A. Relman. “The Landscape Ecology and Microbiota of the
Human Nose, Mouth, and Throat.” Cell Host & Microbe, vol. 21, no. 4, 2017, pp. 421–
432., doi:10.1016/j.chom.2017.03.011.
Landscape ecology refers to the
relationships between spatial arrangement
and processes that give rise to patterns in
local community structure. Spatial analysis
of the unique mouth, nose, and throat
landscapes can help us to further
understand the physiological factors that
govern microbial community composition,
function, and ecological traits that underlie
health and disease.

18. The Mouth-
Body
Connection

19. Rosier, B.t., et al. “Resilience of the Oral Microbiota in Health: Mechanisms That
Prevent Dysbiosis.” Journal of Dental Research, vol. 97, no.4, 2017, pp
371380.,doi10.1177 /002203451774 2139.
Health-maintaining mechanisms that
limit the effect of disease drivers
involve interrelationships that
develop within dental biofilms and
between biofilms and the host. Health
maintaining mechanisms include
ammonia production, limiting drops
in pH that can lead to caries, and
denitrification.

20. Nikitakis, Ng, et al. “The Autoimmunity-Oral Microbiome Connection.” Oral Diseases, vol. 23, no. 7,
2016, pp. 828–839., doi:10.1111/odi.12589.
Increasing evidence links dysbiosis of the oral microbiome to various autoimmune
diseases such as Sjögren’s Syndrome (SS), Systemic lupus erythematous (SLE), Crohn’s
disease (CD), and Rheumatoid arthritis (RA).
Babu, Nchaitanya, and Andreajoan Gomes. “Systemic Manifestations of Oral Diseases.” Journal of
Oral and Maxillofacial Pathology, vol. 15, no. 2, 2011, pp. 144–147., doi:10.4103/0973-029x.84477.
The oral cavity might well be thought of as the window to the body as oral manifestations
accompany many systemic diseases. Three mechanisms or pathways linking oral infections to
secondary systemic effects have been proposed: metastatic spread of infection from the oral cavity
as a result of transient bacteremia, metastatic injury from the effects of circulating oral microbial
toxins, and metastatic inflammation caused by immunological injury induced by oral
microorganisms.

21. Nelson-Dooley, Cass. “The Mouth, the Oral Microbiome, and Systemic Inflammation.” Health First
Consulting, 27 Jan. 2018, healthfirstconsulting.com/uncategorized/the-mouth-the-oral-microbiome-
and-systemic-inflammation/.
The link between oral health and systemic health may be explained by periodontal pathogens.
The periodontum presents a large, inflamed surface area that is rich in dysbiotic microbes.
Frequent transient bacteremia exposes the system to chronic, low-grade inflammation.
Parashar,Amit, et al. “Interspecies Communication in Oral Biofilm: An Ocean of Information.” Oral
Science International, vol. 12, no. 2, 2015, pp. 37–42., doi:10.1016s1348-8643 (15)00016-6.
Within oral biofilms, resident bacterial cells interact with one another and exchange messages in the
form of signaling molecules and metabolites. Signaling between bacteria may have important
implications for the virulence of oral pathogens. When assessing the ability of oral bacteria to cause
disease, it is essential to consider the community in its entirety.

22. Moutsopoulos, Niki M., and Joanne E. Konkel. “Tissue-Specific Immunity at the Oral Mucosal
Barrier.”Trends in Immunology, vol. 39, no. 4, 2018, pp. 276–287., doi:10.1016/j.it.2017.08.005.
The gingiva is a constantly stimulated dynamic environment where homeostasis is often
disrupted resulting in the common inflammatory disease, periodontitis. Unique signals tailor
immune functionality at the gingiva where a specialized network polices this oral barrier.
Rosier, B.t., et al. “Resilience of the Oral Microbiota in Health: Mechanisms That Prevent
Dysbiosis.” Journal of Dental Research, vol. 97, no. 4, 2017, pp. 371–380., doi10.1177/002203
4517742139.
The transition from periodontal health to disease is associated with a dramatic shift from a symbiotic
microbial community to a dysbiotic microbial community composed mainly of anaerobic genera.
Persistence of dysbiotic oral microbial communities can mediate inflammatory pathology at local as
well as distant sites outside of the oral cavity.

23. Beyond
Bacteria

24. Witherden, Elizabeth A., et al. “The Human Mucosal Mycobiome and Fungal
Community Interactions.” Journal of Fungi, vol. 3, no. 4, July 2017, p. 56.,
doi:10.3390/jof3040056.
There are various fungal communities
within our mouths that interact with
bacterial communities. These fungal
communities show significant
variation within different body
habitats and within changes in disease
status. Such variations have a
significant role in host homeostatic
responses and pathologies.
Oral Microbiome
Gut Microbiome
Oral Mycobiome
Gut Mycobiome

25. Lof, Marloes, et al. “Metabolic Interactions between Bacteria and Fungi in Commensal
Oral Biofilms.” Journal of Fungi, vol. 3, no. 3, 2017, p. 40., doi:10.3390/jof3030040.
The healthy oral cavity is characterized by great microbial diversity, including both bacteria
and fungi. In the oral cavity of healthy individuals, over 100 fungal species have been
identified, with Candida as the most prevalent species. Presence of C. albicans in biofilm
decreases cariogenic potential of plaque by decreasing acidity within the mouth.
Sultan,Ahmed S., et al. “The Oral Microbiome: A Lesson in Coexistence.” PLOS Pathogens, vol. 14,
no. 1, 2018, doi:10.1371/journal.ppat.1006719.
The ecological balance in the oral cavity is maintained through antagonistic, as well as
mutualistic, interspecies interactions. Bacterial streptococci have been shown to provide C.
albicans with a carbon source for growth as well as adhesion sites for fungi to persist within the
oral cavity.

26. Ly, M., et al. “Altered Oral Viral Ecology in Association with Periodontal Disease.” MBio, vol. 5, no. 3,
2014, doi:10.1128/mbio.01133-14.
The human oral cavity is home to a large and diverse community of viruses. Most of the
viruses that inhabit the saliva and the subgingival and supragingival biofilms are
predators of bacteria. Dental plaque viruses in periodontitis were predicted to be
significantly more likely to kill their bacterial hosts than those found in healthy mouths.
Baker, Jonathon L et al. “Ecology of the Oral Microbiome: Beyond Bacteria” Trends in
microbiology vol. 25,5 (2017): 362-374.
A comprehensive understanding of the oral microbiota and its influence on host health
and disease will require a holistic view that emphasizes interactions among different
residents within the oral community, as well as their interaction with the host.

27. Parmar, Krupa M., et al. “Intriguing Interaction of Bacteriophage-Host Association: An
Understanding in the Era of Omics.” Frontiers in Microbiology, vol. 8, 2017,
doi:10.3389/fmicb.2017.00559.
Innovations in next-generation sequencing and microbial studies through omics:
genomics, transcriptomics, proteomics, and metabolomics have allowed researchers to
discover phylogenetic affiliation and functions of bacteriophages and their impact on
microbial communities.
Szafrański, Szymon P., et al. “The Use of Bacteriophages to Biocontrol Oral Biofilms.” Journal of
Biotechnology, vol. 250, 10 Jan. 2017, pp. 29–44., doi:10.1016/j.jbiotec.2017.01.002.
Many oral infections such as caries, periodontal disease, and peri-implant disease are induced by
biofilm accumulation influencing quality of life, systemic health, and expenditure. As bacterial
biofilms become increasingly resistant to antibacterial therapy, biocontrol of biofilms through
bacteriophage therapy may be the future of oral treatments.

28. Ly, Melissa, et al. “Altered Oral Viral Ecology in Association with Periodontal Disease.” MBio, vol. 5,
no. 3, 20 May 2014, doi:10.1128/mbio.01133-14.
This study compares oral microbial compositions between healthy individuals and individuals
with periodontal disease. Viruses inhaling dental plaque were significantly different on the basis
of oral health status, while those present in saliva were not. Dental plaque viruses in
periodontitis were predicted to be more likely to kill their bacterial hosts than those found in
health mouths.
Edlund,Anna, et al. “Bacteriophage and Their Potential Roles in the Human Oral Cavity.” Journal of
Oral Microbiology, vol. 7, no. 1, 2015, p. 27423., doi:10.3402/jom.v7.27423.
The oral cavity contains vast oral phage communities that have been implicated in the acceleration
of microbial diversity of their bacterial hosts. Both host and phage mutate to gain evolutionary
advantages through acquisition of new gene functions by lysogenic conversion. Such evolutionary
advantages include antibiotic resistance.

29. Silveira, Cynthia B. “Piggyback-the-Winner in Host-Associated Microbial Communities.” Biofilms
and Microbiomes, no. 2, 6 July 2016, doi:10.1038/npjbiofilms.2016.10.
The Piggyback-the-Winner model suggests that switching to lysogenic life cycles reduces
phage predation control on bacterial abundance. The model predicts that lysogeny is
favored at the top of mucin concentration gradients (biofilms) and lytic predation
predominates in the bacteria-sparse intermediary layers .
Tetz, George, and Victor Tetz. “Bacteriophages as New Human Viral Pathogens.” Microorganisms, vol.
6, no. 2, 16 June 2018, p. 54., doi:10.3390/microorganisms6020054.
Researchers suggest that bacteriophages have different ways to indirectly interact with eukaryotic
cells and proteins, leading to human diseases. Though the underlying mechanisms are not
completely understood, bacterial viruses should be further explored as diagnostic treatment
targets for therapeutic intervention