lecture 2,3,4 - mucosal microbiomes and oral diseases

what are koch’s postulates

1. organism must be present in all cases of disease and absent in healthy

2. organism must be isolated from disease cases producing pure cultures

3. organism must cause disease in healthy individual when introduced

4. organism re-isolated from experimental host must be identical to original host

why are koch’s postulates not true for all?

1. pathobionts = opportunistic microorganisms/ non-infectious agent that can become pathogenic/virulent in the immunocompromised such as candida fungus = thrush

2. not know media to grow organism in so not always see, metagenomic sequencing find unexpected organisms

3. pathobionts disease in immunocompromised but not in healthy

4. not apply to polymicrobial conditions

why are Koch’s postulates not true for H. pylori causing peptic ulcer disease?

1. Pylori not present in non-steroidal anti-inflammatory ulcers (peptic ulcers) so doesn’t cause all peptic ulcers

2. Took culture of pylori, drank it and took H2 antagonists to stop acid production so not a normal healthy individual as normally produce acid as wanted to give pylori a chance to get established so research not conducted properly as koch's postulates not fulfilled

role of the mouth

Digestion

• Intake of food

• Mechanical breakdown – chewing (Hard tissues e.g. teeth)

• Moistens and lubricates - saliva

• Start of digestive process – salivary enzymes

• Formation of bolus – mechanical processes - help swallow food

Respiration

Inlet to upper respiratory tract (mouth breathing)

Speech

Manipulation of sounds (air) - communication

what is the oral mucosa lined by?

 stratified squamous epithelia (lining mucosa) - soft areas of mouth

what do the sites of the mouth involved in chewing (masticatory epithelia) have?

layer of keratin

• on areas of tongue and top of teeth

what is the role of the gums?

gingiva (gums) overlies mandible and maxilla and helps support the teeth

what is the gingival crevice/ sulcus?

lined with non-keratinized epithelium (crevicular epithelium) that thins towards the base where it meets with the tooth

what happens at the base of the gingival sulcus?

epithelium transitions to an incompletely differentiated epithelium (junctional epithelium)

what is junctional epithelium?

 highly permeable allowing constant passage of fluid (gingival crevicular fluid) and cells

what is a microbiome?

Ecological community of commensal, symbiotic and pathogenic microorganisms within a body space or other environment-

Lederberg & McCray 2001

how are microbiomes analysed?

• DNA sequencing - bioinformatics

• targeted microbiome analysis: sequence 16S rRNA gene for bacteria to identify what is present and its abundance

• shot-gun metagenomics: sequencing all the DNA in a sample and using bioinformatics to predict the source/ function of the DNA sequences - what is present, abundance and what its role is

microbiome biogeography

what is dysbiosis?

Abnormality or imbalance of the microbial flora of the intestinal tract or other part of the body, especially when considered as a causative or contributory factor in disease

• change in microbiota from healthy to disease state

Dysbiosis typically features one or more of what non-mutually exclusive characteristics:

• bloom of pathobionts

• loss of commensals

• loss of diversity

what are pathobionts?

• commensals that have the potential to cause pathology

• typically present at low abundance but proliferate when changes in the environment occur (opportunistic pathogens)

why does dysbiosis result in a loss of commensals?

their restoration has the potential to reverse dysbiosis

what are commensals?

normal residing members of the microbiota

why does dysbiosis result in a reduction in diversity?

•  Diversity is associated with metabolic health

• low bacterial diversity is associated with a number of diseases

what are oral diseases associated with dysbiosis?

• Periodontal (gum) disease

• Dental Caries (tooth decay) - disease of hard tissues

• Oral cancer - disease of soft tissues

• Peri-implantitis

• Mucosal diseases

  • Leukoplakia

  • Lichen Planus

what defines a healthy oral microbiome? why not sure?

• Large differences in healthy individuals

• Genetic

• Environmental

• Lifestyle

• Differences in study parameters

  • Experimental design

  • Bioinformatics analysis approaches

 

• Lack of large scale studies

  • 30 million people genome sequences v 10,000 publicly available microbiome data sets

 

• The oral cavity has a distinct biogeography (i.e. the microbiome varies from site to site)

 

• The expanded human oral microbiome database (eHOMD)

what is periodontal disease?

destructive inflammatory disease driven by dysbiosis of the oral microbiota

what is the non-specific plaque hypothesis?

what is the specific plaque/ microbial shift hypothesis?

what is the ecological plaque hypothesis?

what is the keystone pathogen hypothesis?

what is the Polymicrobial synergy and dysbiosis (PSD) model of periodontal disease?

• Periodontitis is initiated by a synergistic and dysbiotic microbiota, within which different members, or specific gene combinations thereof, fulfil distinct roles that converge to shape and stabilize a disease-provoking microbiota

how does dysbiosis drive periodontal disease?

Immune response - not on or off, physiological levels of inflammation

what is osteoclastogenesis?

what is osteoblastogenesis?

what are dental caries?