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Oral Bacteriophages The Little Things that Matter

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Within the oral cavity is an ecosystem comprised of various microbial communities whose interactions, balance, and imbalance can determine the difference between oral health and disease. With recent research linking the oral microbiome to systemic diseases such as heart and lung disease, cancer, and various autoimmune diseases, it is important to understand the little things in the oral cavity that have large impacts on oral health. 

Joining Molecular Med TRI-CON in San Francisco, DrBonnie presents new discoveries on oral bacteriophages—what they are, how they interact with other microbes, and their therapeutic potential to minimize oral diseases. 

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Oral Bacteriophages The Little Things that Matter

  1. 1. Oral Bacteriophages The Little Things That Matter @DrBonnie360
  2. 2. Ad Oral Cavity Anatomy Adapted from: https://www.ncbi.nlm.nih.gov/books/NBK65887.1/figure/CDR0000258017308/?report=objectonly @DrBonnie360
  3. 3. How we study the oral microbiome Adapted from: https://www.nap.edu/read/24960/chapter/6#51 @DrBonnie360
  4. 4. The Oral Microbiome What’s It Influenced By? • Age • Host & Environment • Habitat • Biofilm Maturation and… Adapted from: https://www.researchgate.net/publication/321471672_Resilience_of_the_Oral_Microbiota_in_Health_Mechanisms_That_Prevent_Dysbiosis @DrBonnie360
  5. 5. the little microbes that inhabit it. Adapted from: https://mmbr.asm.org/content/83/1/e00044-18 @DrBonnie360
  6. 6. How we study the oral microbiome • Genomics • Transcriptomics • Proteomics • Bolomics Adapted from: https://www.researchgate.net/publication/233838508_Dental_Caries_from_a_Molecular_Microbiological_Perspective @DrBonnie360
  7. 7. A Multispecies Biofilm All components of the oral microbiome interact to form the biofilm. Including fungi and viruses. Adapted from: https://www.nature.com/articles/nrmicro2381 @DrBonnie360
  8. 8. Oral Biofilm Formation Colonization Formation Adapted from: https://doi.org/10.3390/jof3030040 @DrBonnie360
  9. 9. Meet the little guys Adapted from: https://doi.org/10.1016/j.virusres.2017.07.013 @DrBonnie360
  10. 10. Meet the little guys - fungi Fungal microbiome (mycobiome) can grow, causing disease on mucosal surfaces. Adapted from: https://doi.org/10.1016/j.tim.2013.04.002 @DrBonnie360
  11. 11. Meet the little guys - fungi Multispecies interactions with fungi affect biofilm accumulation. Adapted from: 10.1016/j.tim.2016.12.012 @DrBonnie360
  12. 12. Meet the little guys Adapted from: https://doi.org/10.1016/j.virusres.2017.07.013 @DrBonnie360
  13. 13. Meet the little guys - viruses Adapted from: https://doi.org/10.1016/j.virusres.2017.07.013 @DrBonnie360
  14. 14. Meet the little guys - viruses @DrBonnie360Adapted from: http://library.umac.mo/ebooks/b28055627.pdf
  15. 15. Bacteriophages – Host Interactions How they regulate the environment. Adapted from: https://doi.org/10.3389/fmicb.2017.00559 @DrBonnie360
  16. 16. Bacteriophages – Brief Life Cycles • Lytic vs. Lysogenic Adapted from: https://www.researchgate.net/publication/273447275_Bacteriophage_and_their_potential_roles_in_the_human_oral_cavity @DrBonnie360
  17. 17. Bacteriophage Involvement in Biofilms Adapted from: https://www.nature.com/articles/npjbiofilms201610 @DrBonnie360
  18. 18. Diseases by Oral Biogeography Adapted from: https://link.springer.com/article/10.1007/s13238-018-0548-1 @DrBonnie360 • Caries • Periodontal Disease • Peri-implantitis • Mucosa diseases • Oral cancer
  19. 19. What Happens When Biofilms Accumulate? Accumulation Oral Disease Adapted from: https://doi.org/10.3389/fmicb.2018.00053 @DrBonnie360
  20. 20. What Happens When Biofilms Accumulate? Accumulation Oral Disease Adapted from: https://doi.org/10.3389/fmicb.2018.00053 @DrBonnie360
  21. 21. Viral Composition in Periodontal Disease by Location Adapted from: doi: 10.1128/mBio.01133-14 @DrBonnie360 Saliva Subgingival Plaque Supragingival Plaque
  22. 22. The Mouth – Body Connection Oral Disease Systemic Disease ? Adapted from: https://link.springer.com/article/10.1007/s13238-018-0548-1 @DrBonnie360
  23. 23. What’s Next? Using Phage Therapy to Manage Biofilms Adapted from: https://doi.org/10.3402/jom.v8.32157 @DrBonnie360
  24. 24. Interspecies Interactions of Periodonto-pathogens Adapted from: https://doi.org/10.1016/j.jbiotec.2017.01.002 @DrBonnie360
  25. 25. Potential Targets for Phage Therapeutics Adapted from: https://doi.org/10.1016/j.jbiotec.2017.01.002 Periodonto-pathogens @DrBonnie360
  26. 26. 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
  27. 27. Exploring the Oral Microbial Ecosystem
  28. 28. 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
  29. 29. 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.
  30. 30. 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>
  31. 31. The Biomes of the Oral Cavity TONGUE TEETH SALIVA GUMS EAR, NOSE,THROAT
  32. 32. 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.
  33. 33. 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.
  34. 34. 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.
  35. 35. 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.
  36. 36. 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.
  37. 37. 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.
  38. 38. 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.
  39. 39. 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.
  40. 40. 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.
  41. 41. 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.
  42. 42. 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.
  43. 43. The Mouth- Body Connection
  44. 44. 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.
  45. 45. 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.
  46. 46. 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.
  47. 47. 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.
  48. 48. Beyond Bacteria
  49. 49. 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
  50. 50. 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.
  51. 51. 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.
  52. 52. 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.
  53. 53. 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.
  54. 54. 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
  55. 55. 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

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