Lecture 14 Modulation of Microbiome-microbiome based theraputics Flashcards
What is the intent of modulation of microbiome-based therapeutics?
- Reverse Symbiosis
- Restore Healthy Microbiome
- Get rid of/reduce the burden of disease causing microorganisms
- > Restore health
How does the presence of resident microflora in the gut prevent disease?
- 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
What are Germ-Free Animals?
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
What do Germ-free animals suffer from?
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
How do gut bacteria help w/ nutrient adsorption?
help provide our gut with enzymes that can breakdown food we can’t breakdown/absorb
How does commensal bacteria influence the epithelial barrier?
- 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
What are important mediators in the cross-talk between the microbiota and epithelial cells?
Microbiota-derived short-chain fatty acids (SCFA), a byproduct of metabolism
Which oral disease manifests as inflammation?
Periodontitis which is caused by dysbiosis
How can you modulate the microbiome?
- Probiotics
- Prebiotics
- Symbiotics
- Selective targeting w/ antimicrobial/selective nutritional starvation
_____________ are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host
Probiotics
What is the criteria for a microorganism to be a probiotic?
- 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
What should produce antimicrobial substances against pathogens in order to restore the healthy microbiota composition?
Probiotics
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?
Probiotics
What are some potential roles of probiotics in oral disease?
-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
What is a potential treatment for oropharyngeal candidiasis? (and is considered a probiotic)
Streptococcus salivarius K12- when applied to tongue- have total clearance
Which lactobacillus was found to be very effective against S. mutans?
Lactobacillus fermentum SD6
___________ are selectively fermentable ingredients that allow specific changes in the composition and/or activity of microbiota that allow benefits to the host
Prebiotics: essentially they are food for the good bacteria
-fermentable oligosaccharides that the good bacteria love to eat
What is the criteria for a Prebiotic?
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
________________ combines 1 or more probiotic microorganism with a prebiotic
Symbiotics
What increases the chance of success of probiotic colonization?
the use of prebiotics together with probiotics (symbiotics)
What is the idea behind selective antimicrobial administration/selective nutritional deprivation?
-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
Why can’t antibiotics be used for selective antimicrobial administration?
because antibiotics also kill good bacteria
Nutritional starvation with an iron chelator is used to treat what?
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
What did the community-wide transcriptome find to show why an iron chelator works for individuals with periodontitis?
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
