Joining Discovery on Target 2018 in Boston, for Targeting the Microbiome, DrBonnie presents new discoveries in research, technology, and upcoming companies. Most importantly, DrBonnie360 focuses on the oral microbiome--what is is, the parts of the mouth involved, and its possible relations to heart disease, lung disease, cancer and autoimmune disease. Topics include: Oral Microbiome, Microbial Composition, Dysbiosis, Oral Health, Chronic Disease, Crowdscience, and Oral Probiotics

1. The Oral Microbiome:
The Next Frontier
@DrBonnie360

2. What happens when you
kiss?
doi.org/10.1186/2049-2618-2-41

3. Host genetics
pH
Atmosphere &
redox potential
Temperature
Lifestyle
Oral Hygiene
Receptors for
attachments
Nutrients
Host Defenses
Microbial Interaction
The first meeting place between
the outside environment and
our immune system
Adapted from: https://www.cda.org/Portals/0/journal/journal_102017.pdf

4. Ecological Balance in the
Oral Microbiome
Dysbiosis
-Bad diet
-Poor plaque control
-Low saliva flow
-Altered host defenses
-Lifestyle risk factors
-Broad spectrum
antibiotics
Systemic disease
Oral disease
Host - microbe
interactions perturbed
Symbiosis
Host - microbe
interactions
Microbe - microbe
interactions
-Diet
-Saliva
-Hormones
-Oral Hygiene
-Host Defenses
Adapted from: https://www.cda.org/Portals/0/journal/journal_102017.pdf

5. Factors that
determine
composition
of the oral
microbiota
DOI: 10.1177/0022034517742139

6. The Oral Ecosystem
There are 700
different species of
bacteria that live in
different microbial
sub-habitats: teeth,
tongue, gums,
saliva, ear nose
and throat.
DOI: 10.1016/j.it.2017.08.005

7. Ecology and Microenvironments
of the Mouth, Nose, and Throat
doi.org/10.1016/j.chom.2017.03.011

8. Chinese Tongue Diagnosis
The tongue is
the window
to total body
health

9. Tongue
Plaque
Saliva
Supragingival Plaque
Your Tongue Print
Each individual contains
a unique oral bacterial
community fingerprint.
Even the oral bacterial
communities that inhabit
the tongue plaque and
saliva are clearly distinct
from one another.
DOI:10.1038/s41522-016-0011-0

10. Healthy biofilmOral Cavity
pH
pH
Diseased biofilm
Readily fermentable
carbohydrates
Virulence factors
Low saliva
flow
H2O2
Proteases
Bacteriocins
Oral Biofilms in Health
And Disease
Beneficial commensal
Pathogens
Adapted from: https://www.cda.org/Portals/0/journal/journal_102017.pdf

11. A Multi-Species Biofilm
doi:10.3390/jof3030040

12. Oral bacterial colonization
and biofilm formation
DOI: 10.1038/nrmicro2381

13. The Ecological Plaque Hypothesis
Caries
Stress
Environmental
Change
Ecological
Shift
Disease
Increased
acid
production
Increased
low pH
challenges
mutans streps
lactobacilli
bifidobacteria
(others)
Caries risk
Adapted from: https://www.cda.org/Portals/0/journal/journal_102017.pdf

14. Stress
Host
Response
Environmental
Change
Ecological
Shift
Disease
Increased
plaque
Increased
inflammation
High GCF
flow,
bleeding,
raised pH
& C˚
Gram-
negative
bacteria;
anaerobic;
proteolytic
Gingivitis/
periodontal
disease
The Ecological Plaque Hypothesis
Periodontal Disease
Adapted from: https://www.cda.org/Portals/0/journal/journal_102017.pdf

15. The Oral Microbiome in
Periodontal Disease
doi.org/10.1016/j.imlet.2014.08.017

16. Biofilm extending into
periodontal pocket
Inflamed gingiva
Resorbed bone
Susceptible host
Immunoregulatory
defects and other
risk factors
Homeostasis
Breakdown
PathobiontsCommensals
Symbiotic
microbiota
Dysbiotic
microbiota
Inflammatory tissue
breakdown
InflammationPeriodontitis
Interaction with
complement and
PRRs
Immunological
Pathogenesis
of
Periodontitis
DOI: 10.1016/j.it.2013.09.001

17. Autoimmunity and the
Oral Microbiome
Oral microbiome
changes: environment
genetics, diet &
lifestyle may trigger
pathogenesis
of autoimmune
diseaseCrohn’s Disease
Reduced bacterial
diversity, decrease in
Firmicutes & increase
in Proteobacteria
may trigger
pathogensis
Systemic Lupus
Erythematosus
Autoantibodies
against oral microbial
products may influence
pathogenesis
Rheumatoid
Arthritis
Altered oral microbiome
identified in RA
patients. P. gingivalis
is strongly linked to
pathogenesis
Sjögren’s
Syndrome
Dysregulated immune
response to normal
oral microbiome
may trigger
pathogenesis
Adapted from: doi.org/10.1111/odi.12589

18. The Oral
Microbiome
In
Rheumatoid
Arthritis
DOI: 10.1038/nrmicro.2016.83

19. Healthy Mycobiome Healthy Microbiome
Gut Mycobiome Gut Microbiome
Oral Mycobiome Oral Microbiome
The Oral Mycobiome
doi:10.3390/jof3040056

20. Probiotics Evidence Base
Adapted from: https://www.cda.org/Portals/0/journal/journal_102017.pdf

21. Company What Products Learn More
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support, oral probiotics,
and gut health
PRO-Dental Lozenge -
containing 3 billion CFU
of S. salivarius K12, S.
Salivarius M18, and blend
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Supplemental oral
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microbial science to
manage bacteria and
balance oral ecology
Lozenge contains
pHossident - a patented
blend of cyclodextrin,
vitamin B6, calcium
chloride and sodium
bicarbonate
http://bit.ly/
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22. http://bit.ly/2iKVEQj
@DrBonnie360
drbonnie360@gmail.com
Dr. Bonnie Feldman, DDS, MBA
As Your Autoimmunity
Connection, we consult with
startup companies and
entrepreneurs who are bringing
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
linkedin.com/in/bonniefeldman
+1(310)666-5312
Content & Visual Design by: Hailey Motooka

23. Exploring the Oral
Microbial Galaxy
Image Credit: Dr. Marck Welch

24. 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.
Dysbiosis
-Bad diet
-Poor plaque control
-Low saliva flow
-Altered host defenses
-Lifestyle risk factors
-Broad spectrum
antibiotics
Systemic disease
Oral disease
Host - microbe
interactions perturbed
Symbiosis
Host - microbe
interactions
Microbe - microbe
interactions
-Diet
-Saliva
-Hormones
-Oral Hygiene
-Host Defenses
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.

25. Biological properties that confer stability in the microbiome are important for the prevention of
dysbiosis—a microbial shift toward a disease. Oral health reflects the ability of the oral ecosystem to
adapt to and counteract perturbing stresses, where the oral ecosystem is defined as the oral
microbiota, the saliva and host (mucosal) immunity.
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/
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 control 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.
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.
Devine, Deirdre A. et al. "Modulation of host responses by oral commensal bacteria.”
Journal of oral microbiology 7 (2015). <http://www.journaloforalmicrobiology.net/

26. Bacteria within the oral cavity plays an integral role in biofilm formation. The formation of biofilm of the
plaque is a complex and rapidly evolving process involving several stages of development. Bacteria first
binds 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>

27. Traversing the
Planetary Ecosystems
in Our Mouths
Image Credit: Dr. Marck Welch

28. Tongue

29. 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 in the distinctiveness of
the corresponding microbial
communities.
Tongue
Plaque
Saliva
Supragingival Plaque
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/

30. The characteristics of tongue coating are very important symbols 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.
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.

31. Teeth

32. Microbial communities of the
tooth surface and irregularities in
the enamel differ with respect to
diversity and richness. Surfaces
and sites with highest diversity
and richness within ecological
niches are most susceptible to
caries. When caries are
established, the acid environment
reduces the diversity and richness
of the local microbiota.
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.

33. 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,
and shows features of the classic biofilm
Struzycka, Izabela. “The Oral Microbiome in Dental Caries.” Polish Journal of Microbiology, vol. 63,
no. 2, Feb. 2014, pp. 127–135.
During conditions of health or disease, the oral environment is constantly undergoing cycles of
demineralization and remineralization on tooth surfaces. When the demineralization and
remineralization equilibrium shifts to a net loss of hydroxyapatite, tooth decay occurs.
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.

34. Saliva

35. 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.
Early Dysbiosis
PROTEOLYTIC
ADAPTIVE
SACCHAROLYTIC
SPECIALIZED
Lipid Degradation
Amino Acid
Fermentation
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>.

36. 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>.
Recent advances in genomics and related ‘omics’ is 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.
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/>.
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 state such as
caries, gingivitis and periodontal disease. Thus, organismal structure of saliva microbiota can potentially
serve as a proxy to the oral health of the host through site-specific signatures and functional profiles of
the saliva microbiota.
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>.
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 complete 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 fungi may have been
overlooked.

37. 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, signaling
between the bacteria and its role in pathogenesis, and the transfer of DNA between bacteria.

38. Gums

39. The 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 disease microbiome
to be enriched in virulence
factors, and adapted to a
parasitic lifestyle that takes
advantage of the disrupted
host homeostasis.
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.

40. 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, cardiovascular and respiratory diseases. Levels of potassium in the periodontal pocket
could be an important element in of dysbiosis in the oral microbiome.
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.
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.
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>.
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,
cardiovascular and respiratory diseases. Levels of potassium in the periodontal pocket could be an
important element in of dysbiosis in the oral microbiome.
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.
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. “Periodontitis: from Microbial Immune Subversion to Systemic
Inflammation.” Nature Reviews Immunology, vol. 15, no. 1, 2015, pp. 30–44., doi:
10.1038/nri3785.

41. 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, which fuels a self-feeding cycle of escalating dysbiosis and
inflammatory bone loss, potentially leading to tooth loss and systemic complications.

42. Ear Nose
& Throat

43. Landscape ecology refers to the relationships between spatial arrangement
and processes that give rise to patterns in local community structure. The
mouth, nose, and throat are all different landscapes that, when analyzed
spatially, can help to further understand the physiological factors that govern
microbial community composition, function, and ecological traits that
underlie health and disease.
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.

44. Connecting the
Constellations
Image Credit: Dr. Marck Welch

45. Health-maintaining mechanisms
that limit the effect of disease
drivers involve inter relationships
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.
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.

46. 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).
Nikitakis, Ng, et al. “The Autoimmunity-Oral Microbiome Connection.” Oral Diseases, vol. 23, no. 7,
2016, pp. 828–839., doi:10.1111/odi.12589.
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,
cardiovascular and respiratory diseases. Levels of potassium in the periodontal pocket could be an
important element in of dysbiosis in the oral microbiome.
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 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.
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/.

47. 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.
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.
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.
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 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.
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.

48. The Next Frontier:
The Mycobiome and
The Virome
Image Credit: Dr. Marck Welch

49. Oral MicrobiomeOral Mycobiome
Gut MicrobiomeGut Mycobiome
There are various fungal communities within our mouths that engage with
other bacterial communities. These fungal communities show significant
variation between different body habitats and with changes in disease status.
Such variations have a significant role in host homeostatic responses and
pathologies.
Healthy Mycobiome Healthy Microbiome
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.

50. The healthy oral cavity is represented by a 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 decrease the cariogenic potential of
plaque by decreasing acidity within the mouth.
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 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.
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 human oral cavity is home to a large and diverse community of viruses. Most of the viruses present
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.
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.