Postbiotic Bacteriotherapies Flashcards
helminthic therapy
an experimental type of immunotherapy, is the treatment of autoimmune diseases and immune disorders by means of deliberate infestation with a helminth or with the eggs of a helminth.
the Chinese weight-loss drug ephedra
alters the microbiome
If your microbiome is not intact, three major classifications of cancer drugs absolutely cannot work in the body.
These drugs include oligonucleotide therapies, platinum chemotherapy, and cyclophosphamide chemotherapy
probiotic rebiosis
key word! :)
Probiotics are now viewed as
delivery systems for neuroactive compounds.
studies in mice found that treatment with the probiotic bacterium Lactobacillus rhamnosus GG
is just as effective in controlling obsessive-compulsive disorder as is the drug Prozac.
probiotic supplementation in human petrochemical-industry workers
was found to reduce their symptoms of depression and anxiety
Bacterial metabolites like short-chain fatty acids, tryptophan metabolites, indole metabolites, and sphingolipids
will be useful new drugs in the fight against NCDs.
polysaccharide A
a component of the bacterium Bacteroides fragilis; can dampen the immune system in cases of autoimmune disease and holds promise for treating diseases such as multiple sclerosis.
short-chain fatty acids (SCFAs)
a fermentation product of specific gut bacteria
sphingolipids produced by gut bacteria can improve brain function and prevent dementia
microbiome-based therapeutics
Microbial metabolites
sugars, fatty acids, and lipid compounds as well as alcohols, ketones, aldehydes, and gases like sulfide and methane.
sulfur-containing compounds such as the sulforaphane
found in broccoli, Brussels sprouts, kale, mustard greens, and cabbage; reported anticancer qualities and apparent benefits to patients with autism spectrum disorder.
having a more diverse skin microbiome
tended to protect you from the mosquitoes
Staphylococcus bacteria
very attractive to mosquitoes
Pseudomonas and Variovorax
were unattractive; the chemicals our microbes produce
competitive exclusion
where probiotic bacteria are used to swamp out other less desirable bacteria, proposals have been made to use replacement bacteria in specific body locations (e.g., underarms) as natural deodorants.
supplementation with the probiotic bacteria Bifidobacterium bifidum R0071
resulted in a higher percentage of healthy days among academically stressed students.
consumption of fermented foods containing probiotics
was associated with reduced social anxiety.
The lower the abundance of Akkermansia muciniphila
the thinner a person’s mucus layer, and the more LPS they have in their blood.
It is even possible to make people profoundly, though temporarily, depressed
by depleting their bodies’ tryptophan supplies.
Describe postbiotic bacteriotherapies
target downstream signaling pathways of the microbiome and act by mitigating the negative effects of an excess, scarcity, or dysregulation of metabolites involved in these pathways
Describe propionate pharmacokinesis
Major component of SCFAs
Produced by Clostridia
Pharmacokinetics
refers to the movement of drug into, through, and out of the body—the time course of its absorption, bioavailability, distribution, metabolism, and excretion.
Functional genomics
-> the study of how a particular subject will respond to a particular drug
Pharmacogenetics
-> the study of variability in drug responses attributed to genetic factors in different populations
Metabolite
-> an intermediate or end-product in metabolism reactions
Bioactivation
-> conversion of a substance into an active state within a living organism or by a biological system
Pharmacogeneticists are primarily interested in
- the genetic variations that alter the ability of the body to absorb, transport, metabolise, or excrete drugs and their metabolites
- Basically: ‘any genetically determined variation in response to drugs’
- Even more basically: ‘the genomic information that gives rise to individual drug responses’
- personalised medicine!!!
Combinatorial pharmacogenetics is essentially
the ‘interrogation’ (hybridization) of a candidate pathway to identify the loci that modulate a drug response
Differing drug responses
‘external compounds have to follow a succession of oxidation reactions and conjugations by metabolizing and transporting enzymes to be assimilated and then secreted by an organism’
Pharmokinetics has 4 components:
absorption, distribution, metabolism and excretion (ADME)
Absorption
-> how the drug enters the bloodstream after taking pill/inhalant (note! Intravenous injection circumvents absorption by putting the drug directly into the blood)
Distribution
-> where the drug travels after absorption, and how much reaches the target site (can be hindered, for example by BBB)
‘high risk pharmacokinetics’
-> when a drug is metabolized by a single pathway
Scenario 1: the prodrug must be metabolized (undergo bioactivation)
What can go wrong?
i) poor metabolisers suffer decreased efficacy or ii) if multiple drugs that inhibit bioactivating systems are administered at once, an extensive metaboliser produces a ’phenocopy’ of a poor metaboliser
Scenario 2: the substrate drug undergoes bioinactivation via a single metabolic pathway
What can go wrong?
If this pathway is faulty, the active parent drug will accumulate in much higher concentrations
Personalised medicine
- ‘pre-prescription genotyping’ or ‘pre-emptive genotyping’, where prescriptions can be made on readily-available genotype data at your GP
- GP could then observe your gene variants, which are their associated drug responses, and hence decide drug type and dosage for maximum efficacy and to avoid adverse drug reactions
- use of genotypes as entry and stratification criterion in clinical trials
