Lecture 14 Modulation of Microbiome-microbiome based theraputics

Question 1

What is the intent of modulation of microbiome-based therapeutics?

Answer 1

• Reverse Symbiosis
• Restore Healthy Microbiome
• Get rid of/reduce the burden of disease causing microorganisms
• > Restore health

Question 2

How does the presence of resident microflora in the gut prevent disease?

Answer 2

• by reducing the chance of colonization by exogenous species: provide competition for physical space & nutrients
• role in development & nutrient adsorption
• role in educating the host immune response
• Having a Healthy microbiome

Question 3

What are Germ-Free Animals?

Answer 3

animals that’s gut and skin are free of bacteria and thus highly susceptible to disease, so that if they are introduced to a conventional environment, they suffer from diarrhoea and have a high death rate

Question 4

What do Germ-free animals suffer from?

Answer 4

the gut of germ-free animals is poorly developed so:

• suffer from an enlarged caecum, poor nutrient adsorption, and from vitamin deficiencies (role in development & nutrient absorption
• The development of the host defenses is impaired

Question 5

How do gut bacteria help w/ nutrient adsorption?

Answer 5

help provide our gut with enzymes that can breakdown food we can’t breakdown/absorb

Question 6

How does commensal bacteria influence the epithelial barrier?

Answer 6

• structural components & metabolites act on epithelial cells and local innate leukocytes to maintain barrier integrity and regulate immune homeostasis
• microbiota-derived short-chain fatty acids (SCFA), a byproduct of metabolism, are important mediators in the cross-talk between the microbiota and epithelial cells
• studies in animals indicate a role in prevention of inflammation

Question 7

What are important mediators in the cross-talk between the microbiota and epithelial cells?

Answer 7

Microbiota-derived short-chain fatty acids (SCFA), a byproduct of metabolism

Question 8

Which oral disease manifests as inflammation?

Answer 8

Periodontitis which is caused by dysbiosis

Question 9

How can you modulate the microbiome?

Answer 9

• Probiotics
• Prebiotics
• Symbiotics
• Selective targeting w/ antimicrobial/selective nutritional starvation

Question 10

_____________ are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host

Answer 10

Probiotics

Question 11

What is the criteria for a microorganism to be a probiotic?

Answer 11

• advisable that be of human origin & niche-specifc
• Probiotic cultures should be recognized as safe for human consumption thru scientific evidence or experiments
• Preparation of large-scale probiotics should be feasible, & its very important that these microorganisms are viable & active in the vehicles in which they are incorporated
• Should adhere to human cells that improves their persistence & allow their growth to favor the competition exclusion of potential pathogens off of the mucosal surface
• Should produce antimicrobial substances against pathogens in order to restore the healthy microbiota composition
• must be safe when ingested thru food consumption & during clinical use, even for immunocompromised individuals
• must have their safety & efficiency established thru randomized & placebo-controlled clinical trials

Question 12

What should produce antimicrobial substances against pathogens in order to restore the healthy microbiota composition?

Answer 12

Probiotics

Question 13

What should adhere to human cells that improves their persistence & allow their growth to favor the competition exclusion of potential pathogens off of the mucosal surface?

Answer 13

Probiotics

Question 14

What are some potential roles of probiotics in oral disease?

Answer 14

-competition for adhesion sites
-aggregate
-compete for nutrients & growth factors
-produce antimicrobial compounds,
-enhance the host immune response
all leading to the reduction of inflammation & tissue destruction

Question 15

What is a potential treatment for oropharyngeal candidiasis? (and is considered a probiotic)

Answer 15

Streptococcus salivarius K12- when applied to tongue- have total clearance

Question 16

Which lactobacillus was found to be very effective against S. mutans?

Answer 16

Lactobacillus fermentum SD6

Question 17

___________ are selectively fermentable ingredients that allow specific changes in the composition and/or activity of microbiota that allow benefits to the host

Answer 17

Prebiotics: essentially they are food for the good bacteria

-fermentable oligosaccharides that the good bacteria love to eat

Question 18

What is the criteria for a Prebiotic?

Answer 18

the fermentability should be demonstrated in in Vitro tests that stimulate, for example, the physiological conditions found in the human niche

• promising substrates should be evaluated in randomized & placebo controlled clinical trials, in order to confirm the positive outcomes obtained by in vitro studies
• Should be a selective substrate for 1 or more beneficial commensal bacteria, whch arie stimulated to multiply and/or are metabolically activated, beneficially altering the microbiota composition of the host

Question 19

________________ combines 1 or more probiotic microorganism with a prebiotic

Answer 19

Symbiotics

Question 20

What increases the chance of success of probiotic colonization?

Answer 20

the use of prebiotics together with probiotics (symbiotics)

Question 21

What is the idea behind selective antimicrobial administration/selective nutritional deprivation?

Answer 21

-applying an antimicrobial that “only” harms the bad microorganism
and causes minimal harm to beneficial bacteria
if we can use a antimicrobial that selects for a keystone pathogen & eliminates it then it could possibly kill other closely related strains

Question 22

Why can’t antibiotics be used for selective antimicrobial administration?

Answer 22

because antibiotics also kill good bacteria

Question 23

Nutritional starvation with an iron chelator is used to treat what?

Answer 23

Oropharyngeal candidiasis
-Iron chelator is selective removal of a keystone pathogen b/c when you have an active infection that pathogen is in high abundance and have high nutritional requirements (more metabolically active) so the iron chelator will affect that pathogen more than the other good bacteria in the oral cavity b/c good bacteria are metabolically less active

Question 24

What did the community-wide transcriptome find to show why an iron chelator works for individuals with periodontitis?

Answer 24

they found gene expression functions of ferrous iron transport and cellular iron ion homeostasis to increase in those with periodontitis so iron chelator is selective for that