Microbiota Transplantation Workshop: Oral Cavity

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1 Microbiota Transplantation Workshop: Oral Cavity December 3, 2015 Floyd E. Dewhirst, DDS, PhD Department of Microbiology The Forsyth Institute

2 Outline Microbiota of the oral cavity Diseases of oral dysbiosis Current therapies Candidate conditions for transplantation Status of transplantation research Risks, safety concerns, or adverse events

3 Oral Microbiome Beginnings Anton Van Leeuwenhoek 1674

4 Oral Microbial Diversity 233 Firmicutes 122 Bacteroidetes 114 Proteobacteria 91 Actinobacteria 49 Spirochaetes 37 Fusobacteria 12 TM7 11 Tenericutes 10 Synergistetes 3 GN02 3 SR1 1 Chlamydiae 1 Chloroflexi

5

6 HOMD Status Report Taxa: 688 Named 344 (50%) Unnamed 100 (15%) Phylotypes 244 (35%) Cultivated 444 (65%) Uncultivated 244 (35%)

7 HOMD Status Report Genomes: 1,340 Representing 368 oral species 53% of All taxa 83% of Cultured taxa Utility: Proteomics Transcriptomics Metabolomics

8 Biogeography Supragingival Subgingival Attached gingivae Tongue dorsum Cheek Palate Tonsils Throat Saliva

9 Relative abundance by site

10 Culturing uncultivated bacteria Haemophilus sp. HOT-036 Leptotrichia sp. HOT-221 Alloprevotella sp. HOT-308 TM7 sp. HOT-349 GN02 sp. HOT-872 SR1 sp. HOT-874 Prevotella sp. HOT-304 Lachnospiraceae sp. HOT-100 Subj-16-AttachGing Subj-04-Throat Subj-02-Saliva Subj-14-SubGing-1 Subj-15-Palate Subj-11-SubGing-1 Subj-02-Tonsil Subj-11-SupraGing

11 Major oral diseases Caries (tooth decay) Periodontal disease (gum disease) Alveolar osteitis (dry socket) Otitis media (middle ear infection) Tonsillitis Strep throat

12 Distant diseases associated with oral bacteria Distant infections Bacterial endocarditis Brain, liver, lung, & bone abscesses Systemic diseases Cardiovascular disease Stroke Preterm birth and low birth weight

13 Periodontitis Most older adults have minor amount 10% of adults have severe periodontitis Disease requires bacteria Not a typical exogenous infection Thought to be caused by subtle immune and inflammatory response defects Dysbiosis with Porphyromonas gingivalis being a keystone pathogen

14 Current therapeutic approaches Scaling and root planing Surgery Antibiotics Biological control of keystone species Vaccination Prebiotics and probiotics Transplantation

15 Mouth to mouth: Kissing transfers 80 million bacteria LA Times, November 19, Shaping the oral microbiota through intimate kissing Microbiome 2014, 2:41. DOI /

16 Caries Bacteria convert sugars to acids which dissolve tooth minerals Episodes of acid production and low ph in tooth microbial plaque lead to elimination of normal acid sensitive bacteria leads to a community of only acidogenic and aciduric bacteria Behavioral disease sugar intake

17 Current therapeutic approaches Pits and fissures can be sealed Teeth can be made more acid resistant by fluoride treatments Cavities filled or teeth extracted Behavioral Eliminate sugar containing beverages water, tea, or wine Targeted elimination of Streptococcus mutans Vaccines Smart bombs Wen Shi Probiotics

18 Transplantation of oral microbiome Fecal transplantation for C diff is not a general model Oral scientists attempting to understand resiliency in the various oral microbiomes and the dysbioses that occur in diseases Periodontitis: targeted elimination of keystone species P. gingivalis Caries: targeted elimination of S. mutans and replacement of normal plaque

19 Directions Future therapies for oral diseases will attempt to shape, not eliminating oral microbiomes Therapies will likely attempt to eliminate keystone pathogens or add selected species to push microbiome composition in a desired direction. Need a regulatory framework that facilitates human oral transplantation research without opening the field to unproven pre- and probiotic therapies from the supplement industry.

20 The End

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