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Chew on This! The Oral Health Revolution


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Newest research connecting the oral microbiome to systemic diseases such as heart and lung diseases, cancer, autoimmune diseases, and even possibly Alzheimer's disease, has shed new light on the importance of oral health.

Joining the 2nd AIRS International Conference on Genomics and Microbiomics in Barcelona, DrBonnie presents new discoveries in research, technology, and upcoming companies focusing on bringing oral care to the forefront of health and well-being.

Published in: Health & Medicine
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Chew on This! The Oral Health Revolution

  1. 1. Chew on this! The oral health revolution
  2. 2. What happens when you kiss?
  3. 3. Did you know? the human oral cavity is home to a rich microbial flora, including bacteria, fungi, and viruses.
  4. 4. Living in microbial sub-habitats: tongue teeth saliva gums ear, nose, throat Operative Dentistry
  5. 5. The oral microbiome is influenced by numerous factors: Journal of Dental Research
  6. 6. These factors affect the balance and imbalance of the oral microbiome Balance – characterized by healthy diet, plaque control, good oral hygiene. Imbalance – influenced by poor diet, inadequate plaque control, lifestyle risk factors, bad oral hygiene.
  7. 7. The transition in biofilm from Balance Imbalance Journal of Fungi
  8. 8. Imbalance can lead to oral diseases in varying biogeographies of the mouth. Protein and Cell
  9. 9. Dental caries occur when acid from bacteria demineralize the enamel. Frontiers in Microbiology
  10. 10. The Ecological Plaque Hypothesis Caries (Tooth Decay) Stres s Environmental Change Ecological Shift Disease Increased acid production Increased low pH challenges mutans streps lactobacilli bifidobacteria (others) Caries risk from:
  11. 11. Periodontal disease occurs when bacteria infiltrate the gum crevices. Frontiers in Microbiology
  12. 12. 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 from:
  13. 13. An estimated 47.2% of American adults have mild to severe gum disease.
  14. 14. The mouth is the first meeting place between the outside environment and our immune systems.
  15. 15. The mouth – body connection oral vascularization allows bad bacteria to travel to other parts of the body. Protein and Cell
  16. 16. Autoimmune diseases with links to the oral microbiome Sjogren’s Syndrome Rheumatoid Arthritis Inflammatory Bowel Disease (IBD) Lupus
  17. 17. So, what can we do?
  18. 18. Food can help maintain the balance of the oral microbiome Drink water– Healthy human saliva has a pH of 7.4. Water helps to normalize the pH of your mouth. Eat Alkaline – Foods such as broccoli, cucumber, and Himalayan salt are high pH (>7) and help to offset acidic foods.
  19. 19. Saliva production is reduced at night time. Night eating correlates with increased dental plaque and gingival inflammation. Limit eating during night time Operative Dentistry
  20. 20. Exercise…but choose low-sugar sports drinks Exercise may improve periodontal disease through activation of the immune system and reduction in inflammatory cytokines. Therapeutics and Clinical Risk Management
  21. 21. What’s new in oral care?
  22. 22. Consumer - based Science - based Convergence of consumer demand and science-based discoveries in oral care
  23. 23. 1. Oral care tools Oral care is now easier and cooler than ever with subscription-based toothbrush plans and a NASA space compound toothpaste formula.
  24. 24. 2. Rinses and mouthwashes New developments and breakthroughs in nanotechnology have offered preventative alternatives which target biofilms and harmful bacteria while promoting re-mineralization.
  25. 25. 3. Supplements The newest products in oral care: probiotics and prebiotics to help balance the oral microbiome and support the growth of ‘good’ bacteria.
  26. 26. Company What Product Learn more Boka combines natural ingredients & modern science to heal your mouth & nourish your body. Toothpaste Contains: nano- hydroxyapatite quip is an oral care company that believes good design in products produces better oral health outcomes. Toothbrush Vibrating brush with automated upkeep Elementa utilizes a new generation of plant based nanosilver technology to neutralize oral acids and reset the biofilm environment in a healthy way. Mouthrinse Nano Silver technology penetrates through plaque barriers, & neutralizes oral acid.
  27. 27. Company What Product Learn more A biotechnology company that developed the world’s first oral probiotic to support mouth and throat health. Probiotic 2.5 billon CFU of S. salivarius strains K12 & M18 Natural and time-released probiotic formulas for women, children, immune support, oral probiotics, and gut health. Probiotic 3 billon CFU of S. salivarius strains K12 & M18 Supplemental oral care prebiotics using microbial science to manage bacteria and balance oral ecology. Prebiotic (SMMRT) to manage oral bacteria m/site/
  28. 28. Phage Therapy
  29. 29. Using phage therapy to manage biofilm formation Journal of Oral Microbiology
  30. 30. Potential bacterial targets for phage therapeutics Journal of Biotechnology
  31. 31. Want to discover more? Email for sample inquiries of oral products Download oral microbiome ebook for more information and tips on how to maintain oral microbial balance Explore all of the research in our visual annotated bibliography (attached to slides below)
  32. 32. 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 (310)666-5312 Content & Visual Design by: Hailey Motooka
  33. 33. Exploring the Oral Microbial Ecosystem
  34. 34. 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
  35. 35. 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, where 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. Egija Zaura et al. “Acquiring and maintaining a normal oral microbiome: current perspective,” Frontiers in Cellular and Infection Microbiology (2014): 85. https://.
  36. 36. Devine, Deirdre A. et al. "Modulation of host responses by oral commensal bacteria.” Journal of oral microbiology 7 (2015). <> 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 of the 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. < biofilms-importance-and-applications/the-role-of-human-oral-microbiome-in- dental-biofilm-formation>
  37. 37. The Biomes of the Oral Cavity TONGUE TEETH SALIVA GUMS EAR, NOSE, THROAT
  38. 38. 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.
  39. 39. 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.
  40. 40. 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, the acid environment reduces the diversity and richness of the local microbiota.
  41. 41. 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, and shows 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 demineralization and remineralization equilibrium shifts to a net loss of hydroxyapatite, tooth decay occurs.
  42. 42. 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.
  43. 43. Glurich, Ingrid et al. “Progress in Oral Personalized Medicine: Contribution of ‘omics.’” Journal of Oral Microbiology 7.0 (2015): 28223. <>. 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. <>. 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.
  44. 44. 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 fungi may have has 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.
  45. 45. 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.
  46. 46. 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, cardiovascular and respiratory diseases. Levels of potassium in the periodontal pocket could be an important element in of dysbiosis in the oral microbiome.
  47. 47. 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. 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. 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/
  48. 48. 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. The mouth, nose, and throat are all different landscapes that, when analyzed spatially, can help us to further understand the physiological factors that govern microbial community composition, function, and ecological traits that underlie health and disease.
  49. 49. The Mouth- Body Connection
  50. 50. 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.
  51. 51. 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. 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.
  52. 52. 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. Nelson-Dooley, Cass. “The Mouth, the Oral Microbiome, and Systemic Inflammation.” Health First Consulting, 27 Jan. 2018, systemic-inflammation/.
  53. 53. 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/ 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.
  54. 54. Lundgren, Jennifer D. “The Relationship of Night Eating to Oral Health and Obesity in Community Dental Clinic Patients.” General Dentistry, vol. 58, no. 3, May 2010. Night eating can negatively effect your oral health. People who engage in night eating often do not brush or floss afterwards, and less saliva is produced at night, both of which can contribute to an increased risk of developing periodontal disease. Obesity and night eating are also heavily correlated. Omori, S et al. “Exercise habituation is effective for improvement of periodontal disease status: a prospective intervention study.” Therapeutics and Clinical Risk Management. 14: 565–574. 2018. Exercise could be a possible therapeutic intervention for periodontal disease. The results showed that there were significantly reduced probing pocket depth (PPD) and number of teeth bleeding on probing (BOP), two commonly used measurements of periodontal disease in the exercise intervention group.
  55. 55. Beyond Bacteria
  56. 56. 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 engage with 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. Oral Microbiome Gut Microbiome Oral Mycobiome Gut Mycobiome
  57. 57. 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 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 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.
  58. 58. 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.
  59. 59. 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.
  60. 60. 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.
  61. 61. 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. Piggyback the winner model suggests that switching to lysogenic life cycle 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 target for therapeutic intervention