This PowerPoint presentation provides a thorough exploration of the oral microbiome and its significance in both maintaining health and contributing to disease. Beginning with an introduction to the oral microbiome, the presentation outlines its diverse composition and its crucial role in oral health. It further examines the concept of dysbiosis within the oral microbiome, highlighting the factors contributing to imbalance and its implications for oral and systemic health. The presentation also delves into emerging research linking oral microbiome dysbiosis to systemic diseases, shedding light on potential mechanisms and clinical implications. Methods for studying the oral microbiome are discussed, along with recent advancements in research methodologies and therapeutic strategies targeting microbial dysbiosis. Additionally, the presentation explores the evolving field of precision dentistry and its integration with oral microbiome analysis for personalized treatment approaches. Through case studies and examples, the audience gains insight into the practical applications of oral microbiome research. The presentation concludes with a summary of key points and an invitation for questions and discussion, emphasizing the importance of ongoing research in understanding and harnessing the potential of the oral microbiome for improving health outcomes.

1. ORAL
MICROBIOME
UMNA FATIMA
M.Sc(P), BIOMEDICAL
SCIENCES
JAMIA HAMDARD UNIVERSITY

2. INTRODUCTION
 Oral microbiome, oral microbiota or oral microflora refers to the
microorganisms found in the human oral cavity.
 Oral microbiome was first identified by the Dutchman Antony van
Leeuwenhoek who first identified oral microbiome using a
microscope constructed by him.
 In 1674, he observed his own dental plaque and reported “little
living animalcules prettily moving.”
 Oral microbiome is defined as the collective genome of
microorganisms that reside in the oral cavity.

3. The oral cavity has two types of surfaces on which bacteria can
colonize: the hard and the soft tissues of teeth and the oral mucosa,
respectively. The teeth, tongue, cheeks, gingival sulcus, tonsils, hard
palate and soft palate provide a rich environment in which
microorganisms can flourish. The surfaces of the oral cavity are
coated with a plethora of bacteria, the proverbial bacterial biofilm.

5. COMPOSITION OF ORAL MICROBIOME
 The microbial ecology of the oral cavity is
complex and is a rich biological setting with
distinctive niches, which provide a unique
environment for the colonization of the
microbes.
 These niches include the gingival sulcus, the
tongue, the cheek, the hard and soft palates,
the floor of the mouth, the throat, the saliva
and the teeth.

6.  The normal microbiome is formed by bacteria,
fungi, viruses, archaea and protozoa.
 There is a symbiotic relationship between the
microorganisms in our oral cavity based on mutual
benefits. The commensal populations do not cause
harm and maintain a check on the pathogenic
species by not allowing them to adhere to the
mucosa.
 The bacteria become pathogenic only after they
breach the barrier of the commensals, causing
infection and disease.

7. The principal bacterial genera found in the healthy oral cavity are
as follows:
Gram positive:
Cocci – Abiotrophia, Peptostreptococcus, Streptococcus,
Stomatococcus
Rods – Actinomyces, Bifidobacterium, Corynebacterium, Eubacterium,
Lactobacillus, Propionibacterium, Pseudoramibacter, Rothia.
Gram negative:
Cocci – Moraxella, Neisseria, Veillonella
Rods – Campylobacter, Capnocytophaga, Desulfobacter, Desulfovibrio,
Eikenella, Fusobacterium, Hemophilus, Leptotrichia, Prevotella,
Selemonas, Simonsiella, Treponema, Wolinella.

8. NON-BACTERIAL MEMBERS OF ORAL CAVITY
 The oral cavity contains diverse forms of microbes such as
protozoa, fungi and viruses.
 Entamoeba gingivalis and Trichomonas tenax are the most
commonly found protozoa and are mainly saprophytic.
 Candida species is the most prevalent fungi seen associated
with the oral cavity.
 Ghannoum et al. carried out culture-independent studies on
twenty healthy hosts and reported 85 fungal genera.
 The main species observed were those belonging to Candida,
Cladosporium, Aureobasidium, Saccharomycetales,
Aspergillus, Fusarium and Cryptococcus.

9. physiological, metabolic and immunological functions which
include digestion of food and nutrition; generation of energy,
differentiation and maturation of the host mucosa and its
immune system
control of fat storage and metabolic regulation; processing and
detoxification of environmental chemicals; barrier function of
skin and mucosa
maintenance of the immune system and the balance between
pro-inflammatory and anti-inflammatory processes
promoting microorganisms (colonization resistance) and
prevention of invasion and growth of disease.
FUNCTIONS OF ORAL MICROBIOME

10. ORAL MICROBIOME AND SYSTEMIC
HEALTH
 Symbiotic and commensal microorganisms
contribute to pathogen resistance, improve the
efficiency of the immune system, and help with
different organ functions.
 As the human mouth is heavily populated by
various microorganisms, the oral cavity microbiome
is one of the main causes of most dental and
periodontal diseases.

11.  As the oral cavity is the primary point of entry to the
digestive and respiratory tracts, maladaptation or
microbial imbalance in the oral cavity is also associated to
oral inflammation, and may lead to systemic diseases in
the human body through microbial pathways such as
bacteremia.
 Oral microbiome have also proven to present risk factors
for human health, such as tumor formation, diabetes
mellitus and other bacterial diseases.

12. 1. PERIODONTAL DISEASE
 Periodontal (gum) disease is an infection of the tissues that
hold your teeth in place.
 It's typically caused by poor brushing and flossing habits that
allow plaque—a sticky film of bacteria—to build up on the
teeth and harden. In advanced stages, periodontal disease can
lead to sore, bleeding gums; painful chewing problems; and
even tooth loss.
 Periodontal disease can originate from various sources, but
the most common source would be a lack of oral hygiene,
which could trigger pathogens residing in the periodontal
pocket to cause inflammation.

13.  Microbial perturbations caused by pathogens such as P.
gingivalis can disrupt the equilibrium maintained in the oral
microbiome environment.
 The perturbations would change the original nutrient needs
of the community, which can disrupt both symbionts and
pathobionts in the environment.
 The competition between different microbial species in the
host can also cause the disruption of the equilibrium, which
can also cause bacteriophagic activity and increase the
pathogenic potential within the oral microbiome
community.

15.  Periodontal disease results in complex immunological responses,
as innate immunity works to prevent damage to the oral tissue
caused by the disruption in periodontal tissue homeostasis.
 The T helper cells are the primary cells that infiltrate oral tissues
in human gingivitis
 During the change, the role of the immune response within the
gingiva would also be affected. Indeed, the initial immune
response of the gingiva is to recruit and activate neutrophils in
order to destroy pathogenic bacteria, although the immune
response would also cause chronic infiltration of T, B and plasma
cells during the change.
 Immune cells would become chronically infiltrated, thus causing
periodontitis, which would present signs such as vascular
proliferation, damaged connective tissues, and alveolar bone
destruction

16.  The observation that periodontal disease can be caused by
more than one pathogen has led to the dysbiosis theory.
 This theory proposes that a composition shift of low-
abundance pathogenic species of bacteria, such as P.
gingivalis, within the oral microbial community in the
periodontal pocket would alter the host microbial
environment, which would ultimately enhance the destructive
effect of inflammation and result in the breakdown of bone
tissue.
 While P. gingivalis is present in low cellular density, it is
considered the keystone pathogen for periodontal disease, as it
can act as a virulence factor to alter and depress the host
immune response.

17. 2. ORAL CANCER
Among all American patients diagnosed with oral
cancer every year, about 90 percent of the patients
have oral squamous cell carcinoma.
As oral carcinoma is associated with various routes of
infection, the oral microbiome may contribute to the
formation of oral squamous cell carcinoma in
different forms of pathogenesis through certain
viruses and bacteria.

18.  Classically, the majority of causal agents for oral cancer
have been found to be viruses, especially the Human
papillomaviruses and Human herpesviruses of which the
former are highly associated with oropharyngeal cancer.
 The high-risk (hr) HPVs are known to be the main cause
of oropharyngeal cancer, through the HPV E6 and HPV
E7 oncogenes which inhibit the p53 and retinoblastoma
(Rb) gene proteins in the posterior third of the tongue,
blocking their tumor suppressing action.

19.  Among the members of the oral bacterial community, the
two most influential bacteria are thought to Porphyromonas
gingivalis and Fusobacterium nucleatum.
 Both P. gingivalis and F. nucleatum can downregulate the
expression of the p53 tumor suppressor gene as well as
upregulate kinases and cyclins to induce the cell
proliferation.
 P. gingivalis and F. nucleatum can induce the production
of pro-inflammatory cytokines, which leads to increased
chronic inflammation that could contribute to the
development of oral cancer.

20. Effect of different bacterial species of oral
microbiome in the progression of oral cancer.

21. 3. GASTROINTESTINAL CANCER
 The oral microbiome may have an effect on oral and
gastrointestinal cancer risk through two main
contributing factors, which are local activation of
carcinogens originating from alcohol and smoking.
 Ethanol is not a strong carcinogen, but oral bacteria are
capable of converting ethanol to acetaldehyde, which is a
familiar carcinogen in humans, leading to the exposure
of the oral and gastrointestinal tract to carcinogenic
acetaldehyde.

22. ALCOHOL CONVERSION BY ORAL BACTERIA.

23.  Oral bacteria may also take part in induced activation of
carcinogenic nitrosamines from smoking tobacco.
 The oral microbiota can activate the nitrosamine in
tobacco smoke, nitrosodiethylamine (NDEA), to its
hydroxylated product, which is a potent carcinogen in
humans.
 Tobacco smoking can also lead to increased production
of acetaldehyde by oral bacteria that could lead to
production of both acetaldehyde and nitrosamines.

24. PREVENTIVE MEASURE!!!
The antiseptic mouthwash chlorohexidine can reduce the levels
of salivary acetaldehyde and nitroso-amino acid formation
and secretion in saliva and urine. Usage of chlorohexidine
prior to ethanol consumption can lead to a 50% decrease in
salivary acetaldehyde levels . The chlorohexidine can also
decrease the levels of nitroso-amino acid formation and
excretion in saliva and urine by 30% .

25. 4. DIABETES
 Diabetes is a common endocrine and metabolic disease
caused by insulin deficiency, impaired pancreatic islet
function, or impaired insulin biological action. Diabetes
with poor blood sugar control is a risk factor for
periodontal diseases, and periodontitis is the sixth major
complication of diabetes.
 Oral microbes can affect the occurrence and
development of diabetes by regulating systemic immune
homeostasis.
 Microbial infection can stimulate the immune response
of local periodontal tissues and produce large amounts of
inflammatory cytokines.

26.  These cytokines can enter the circulatory system and affect
multiple system tissues and blood vessels throughout the body.
 The endotoxin of P. gingivalis binds to the CD14 molecules on the
surface of macrophages to activate the TLR2/4 signaling pathway.
 Activated TLR2/4 can bind to the TIR homology domain and the
N-terminal death domain of MyD88 to activate IRAK. The
activated IRAK then binds to TNF receptor-related factors to
activate JNK, MAPK, and NF-κB signal transduction pathway
eventually leading to a chronic inflammatory state.
 NF-κB can inhibit the expression of some important proteins in the
insulin signaling pathway, such as glucose transporter 4 protein
(GLUT4).
 TNFs stimulate fat cells to break down lipids, thereby increasing
the level of free fatty acids in the blood and reducing insulin
sensitivity.
 Persistent inflammation will lead to insulin resistance, which can
further aggravate the systemic inflammatory response and cause a
long-term imbalance of the inflammatory axis, affecting blood
glucose metabolism.

27.  Animal experiments have also confirmed that the
dysbacteriosis caused by periodontitis can promote the
occurrence of insulin resistance in mice on a high-fat diet
through an adaptive immune response.
 The composition of subgingival dental plaque in
diabetics was found to be different compared to non-
diabetic individuals. Sequencing of the 16S rRNA gene
was used to identify differences in subgingival
microbiota between type 2 diabetics and non-diabetics.

28.  Significant differences were observed with diabetics
having higher abundance of TM7, Aggregatibacter,
Neisseria, Actinomyces, Capnocytophaga, Gemella,
Eikenella, Selenomonas, Fusobacteriu, Veillonella,
Streptococus, F. Nucleatum, V. Parvula, Veillonella
dispar, and E. corrodens.
 Considering the hyperglycemic state of diabetic hosts
and their altered immune response, the subgingival
difference between diabetics and non-diabetics could be
a potential risk factor for pathogenicity in oral
microbiome due to dysbiosis of oral microorganisms in
diabetics.

29. Schematic of the oral
microbiota in human
systematic diseases.
Oral microbes affect
the process of
systemic diseases
through the
inflammatory response
caused by oral
infection or the ectopic
colonization of oral
microorganisms in
other organs or tissues
of the human body,
such as tumor, gut,
heart, blood, brain,
joint, placenta.

30. REFERENCES
 https://www.ncbi.nlm.nih.gov/pmc/articles
/PMC8891310/
 https://openprairie.sdstate.edu/cgi/viewco
ntent.cgi?article=1016&context=biomicro
_plan-b
 https://umzu.com/blogs/health/oral-cavity-
anatomy-and-function
THANK
YOU!!