Microbiology and Immunology Exam 2 Class 1 [The Oral Microbiome]

Everyone has a _____ Microbiota

Unique

Highly variable

Different body locations for an individual

Has a different distribution of microorganisms

Different sites of the body matters for microorganisms

This is true

Microorganisms will survive in different

Niches

_____ members tend to harbor more similar microbiota

Family

Why do we see similarities between family members

- Genetic factors (Similar genetic compositions)

- Environmental factors (Because you are in close proximity)

_____ and ______ can strongly affect the composition of the microbiota

Environmental and stochastic factors

The oral cavity contains diverse _____, with distinct microbial communities

ecological niches

The unique niches of the oral cavity have different characteristics such as:

- Oxygen availability

- Nutrients source

- Surface type

- Stability

Parameters affecting colonization

- pH

- Oxygen

- Mechanical forces

- Saliva flow and composition

- Host age

How/why is pH a parameter

normal body pH ~7.2, things like diet and inflammation may change the pH environment and promote different microorganism growth

How/why is Oxygen a parameter

Oxygen amount varies by location. You may have different levels of oxygen dependent species based on available Oxygen

How/Why is saliva flow and composition a parameter

Saliva is essentially a tsunami for bacteria. Big waves of saliva knocking around. It can help in the dispersal of nutrient but also in the dispersal of microorganisms.

How/Why is host age a parameter

Presence of teeth, dentures, hormonal stage, immune function

The microbiome is comprised of

bacteria, viruses, fungi, parasitic eukaryotes

We will be focusing on Bacteria

Many of these microorganisms form unique

shapes and architecture in the oral cavity

ex: Hedgehog shape (looks like corn on the cob)

Why do microorganisms form these unique structures

It gives stability of the biofilm.

- Some of these microorganism are the scaffolding

Based on the location or structure you can see that the distribution of the microorganism

is variable

- Slide about research. Said don't worry much except for the variability of species depending on the surfaces.

What do bacteria use to bind surfaces

Pili, Adhesins

We call strep the

Pioneer colonizers

- Microorganism that are first to attach to many different surfaces

Streptococci are:

- Facultative anaerobes (good for being foundation in biofilm)

- Pioneers, adhere to the pellicle

Largest group of oral bacteria

Streptococci

4 groups of streptococci in the mouth:

- Mitis/Oralis

- Salivarius

- Mutans

- Milleri

Even though there are commensal non-cariogenic oral streptococci they can be

opportunistic pathogens

- especially mitis/oralis group

Veillonella:

- Gram negative cocci

- Strictly anaerobic

Veillonella need a ____

Partner to survive in the oral cavity

- Symbiotic with sugar fermenting organisms

Partner with a strep (mutans)

Why does veillonella need a partner

Becauase they can't break down carbohydrates

Strep mutans break down carbohydrates and produce

Lactate/lactic acid as a biproduct

Veillonella uses _____ to generate energy

Lactate

Strep Mutans and veillonella co-aggregate and are typically found at sites of ____

Caries

Actinomyces

- Gram positive branching rods

- Facultative anaerobes (can grow well in the biofilm)

Architecture of Actinomyces

Can interact with the strep and form a bridge for other microorganisms to attach

Actinomyces provide

a structural feature of the architecture of the biofilm

Actinomyces are also found in areas of

Caries

This is the best bridging Microorganism in the biofilm. Can attach to 10-20 other microorganisms because it is so long

Fusobacterium Nucleatum

Fusobacterium:

- Obligately anaerobic

- Filamentous gram-negative rods

The most common species of F. nucleatum are associated with conditions like

- periodontal disease

- Lemierre's syndrome

- Colorectal cancer

The elongated shape enables F. nucleatum to

interact with many other microbial cells.

When F. nucleatum is co-cultured with strep sanguinis

assembles into highly ordered corncob-like structures, in which upwards of 10 S. sanguinis cells can be bound to a single F. nucleatum cell

over your life your microbiome

stabilizes--> dynamically changes --> goes down

(indirect) Certain pathogenic organism can cross the placenta and can have

Profound influence on the development of the fetus

If the placenta has a microbiome then

Some of those microbes in the placenta may be crossed over to the fetus

- can influence both oral and gut microbiome in baby

The way we deliver the baby

Also is an important factor for the child's microbiome

- Vaginal vs Cesarean delivery

- Vagina has lots of microorganisms

- In a Cesarean the microbiome comes from the skin

If you get the microorganism from the mother it is considered a

Vertical transmission

The placental microbiome has a taxonomic profile that

Is similar to the Oral Microbiome

Two theories on how you can establish the microbiome

- Sterile womb paradigm

- In-Utero Colonization Hypothesis

In the first 6th months

Strep is the predominate species.

Why might you see a shift to different microorganisms in the microbiome

- Eruption of teeth (anarobic bacteria can thrive in subgingival niches)

- Dietary changes (liquid to solid diet)

The diversity of anaerobes increases with age, likely as teeth erupt creating

Subgingival niches

The diversity ______ with age and stabilizes

increases

Healthy individuals with dentures

See some microorganism changes but not to much changes

Abiotic implant surfaces

See microbiome distribution changes depending on how successful the implant is.

Summary: The oral microbiome is

diverse and site specfic

Summary: the composition of the oral microbiome

evolves from birth through adulthood, influenced by delivery mode, diet, oral hygine, hormonal changes, and presence of teeth. Vertical and horizontal transmission shape early colonization

Summary: The placental microbiome shares

similarities with the oral microbiome, challenging the sterile womb paradign

Summary: Summary: Denture wearers show changes in

the composition of microorganism

Summary: Peri-implant sites exhibit

distinct microbial profiles depending on health status (healthy, mucositis, peri-implantitis)

START PART 2

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With a C. Diff infection we need to know

Because of the endospores it is really hard to kill

The healthy homeostasis of the microbiome. The balance of microorganisms

Eubiosis

Disruption of microbiome homeostasis caused by imbalance of microbiota

Dysbiosis

Dysbiosis can result in

Loss of overall diversity.

- Loss of beneficial microbiota and expansion of the bad ones.

Frequent intake of fermentable carbohydrates and sugars drives a shift towards a

more acidic environment, favoring acid tolerant bacteria. This initiates the demineralization of tooth enamel. As the environment remains acidic, bacteria like Strep mutans becomes dominant

Lots of studies that show that microorganisms are associated with

Cancer

How do microorganisms induce cancer

Direct effects:

- Microbial cytotoxins

- Microbial metabolites can act as mutagens

Indirect effects:

- Induction of chronic inflammation

- Deleterious alterations in the microbiome

- Deleterious changes to the host immune response, immune surveillance, and anti-apoptotic

If you have the loss of eubiosis the organisms who have the means to cause cancer can

Increase in number and increase their virulence causing damage to the cells

Summary: Ways Bacteria can cause cancer

1. Hyperactivating the immune system --> leads to more differentiation and division

2. Directly effects genes

3. Microbial derived metabolism affecting carcinogenesis

Oral Squamous Cell Carcinoma

- Associated with genetic factors and behavioral exposures to alcohol and tobacco. Especially in combination. Periodontal disease is also thought to be a risk factor

- Part of a larger family of head and neck cancers

- Arise through an accumulation of genetic and epigenetic changes in gene acting in cancer associated signaling pathways

Prevalence of OSCC

Have a growing amount of cases throughout the world

Emerging research suggests a strong association between OSCC and

the oral microbiota

- Pathogenic bacteria:

Porphyromonas gingivalis and Fusobacerium nucleatum

Summary (again) how oral microbiota dysbiosis is associated with cancer

- Chronic inflammation

- Oncogenic metabolites

- Epithelial Barrier alterations

- Epigenetic modulation (DNA changes)

F. nucleatum is enriched in colorectal cancer, suggesting that

F. nucleatum is closely related to the occurrence of colorectal cancer

What is F. nucleatum's effect in colorectal cancer

- Invade cancer cells and promote the proliferation of cancer cells

- Inhibit the activity of immune cells such as T cells and NK cells (inhibiting the killing of cancer cells)

- Affect cell autophagy and promote the development of tumors

Porphyromonas gingivalis is a gram negative anaerobic coccabacillus is a keystone pathogen associated with periodontal disease and has been linked to numerous...

systemic diseases and complications

Oral Microbiome and Atherosclerosis and Myocardial infarction

Can trigger chronic inflammation and thus formation of atherosclerotic plaques

Oral microbiome and Alzheimers

P. gingivalis can cross blood brain barrier and can cause plaque

Oral microbiome and Rheumatoid arthritis

Virulence factors can change a protein and host recognizes it as its own. Autoimmune response

Diabetes and periodontitis

is bidirectional (chicken or the egg) they are impacting each other but we don't know which comes first

Summary: The dysbiosis of oral microbiota plays a critical role in oral diseases like

Dental caries, gingivitis, periodontitis, and oral thrush and oral cancer

Summary: Dysbiosis of oral microbes is linked to systemic conditions such as

cancer, diabetes, cardiovascular disease, and alzheimers

Systemic impact of oral pathogens P. gingivalis and F. nucleatum are linked to systemic diseases including

colorectal cancer, rheumatoid arthritis, diabetes, and cardiovascular conditions through mechanisms like immune modulation, inflammation, and molecular mimicry