Flashcards in Gut Microbiota Deck (21)
What is the make up of a normal microbiota?
It is mostly composed of anaerobic bacteria (100-1000 fold more than aerobic/facultative anaerobes)
10-fold more unique genes than their host
The most abundant phyla are the firmicutes and bacteroidetes
The collective metabolic activity of these microorganisms is approximately the same as that of the liver which is what has led to suggestions that it is now considered its own organ
What have been the paradigm shifts in immunology as a result of studying the microbiota?
Instead of the immune system recognizing self and non-self there is now the super-organism theory where the microbiota is considered part of self
Host mucosal immune system is tolerant rather than responsive to these microorganisms
There may be an immune system-microbiota alliance
What are the costs of having a complex immune system which is dependent on the microbiota?
Allergic, autoimmune and inflammatory disorders may occur from a failure to control misdirected immune responses against self microbiota derived or environmental antigens
Changes in microbiota composition or function may occur in response to antibiotics, dietary changes and recent elimination of key constituent’s namely helminthes may have transformed our microbial allies into potential liabilities
What are the tools commonly used to study the microbiota?
Next-generation sequencing where there can be comparisons made between the microbiota in patients with disease vs healthy individuals
Germ-free mice where there can be manipulation by antibiotic treatment or microbiota reconstitution
How is the microbiota obtained and maintained?
Our first contact with microorganisms is thought to be during passage through the birth canal with this initial exposure establishing the context for subsequent mucosal and systemic immune function
It is maintained through the actions of tolerance, early exposure to colostrum/breast milk, diet and the environment to which we are exposed
How is there tolerance to the microbiota?
There is a reduced production of inflammatory cytokines with the B and T cell responses skewed towards regulation
How does early exposure to colostrum/breast milk regulate the microbiota composition?
This contains live microbes, metabolites, maternal IgA, immune cells and cytokines and drives the infants microbiota to form with the correct composition
How does diet impact the microbiota?
Dietary changes are capable of rapidly and reproducibly altering the human gut microbiome with evidence suggesting that there are alterations within one day of diet change
What are the possible factors which lead to microbiota symbiosis?
High fibre diet
Environmental exposure to microbes
Prevalence/consumptions of probiotics
What are the possible effects of symbiosis?
Resolution of inflammation
Epithelial barrier integrity
Regulation of neutrophil activity
Regulation of dendritic cell function
A decrease in the proportion of Th17 and increase in the proportion of Treg
What are the possible factors for dysbiosis?
Antibiotic use in children
Antibiotics entering the food chain through livestock
Infection with pathogenic bacteria
What are the consequence of dysbiosis?
Unresolved inflammatory responses
An increase in Th17 to Treg ratio
What is the role of the microbiota in health?
Stimulation and maintenance of the mucosal firewall (through low levels of stimulation of the immune system)
Development of mucosal associated lymphoid tissue (as without a microbiota there is a reduction in mucus production and submucosa development)
Inhibition of pathogen growth (through colonization resistance)
Dampening of immune responses
Priming of mucosal immune responses
What is colonization resistance?
This is one of the key was in which our microbiota protects us from pathogens this is done by occupying the same niche, affecting nutrient availability, stimulating the release of antibacterial products, targeting of related species
How do commensal bacteria interact with CD4 T cells?
They induce their differentiation with species such as clostridium stimulating Treg development and B. fragilis stimulating Th1 development
What is the role of PAMPs and gut homeostasis?
Ongoing exposure to PAMPs stimulates gut immune development
RegIIIgamma is produced in response to MyD88 mediated signalling
Exposure to TLR ligands alone can induce maturation of the germ free gut mucosa
How does TLR-5 mediated signalling provide a link between the microbiota and patient response to vaccination?
WhenTLR5 knockout mice were given a vaccine they develop a response slower than that of those that functional TLR5
As the vaccine does not stimulate TLR5 it is likely that this was a result of microbiota stimulation
Germ free mouse studies have supported this where germ free mice did not generate an effective response to a flu vaccine compared to normal mice
What is the relationship between the microbiota and short chain fatty acids?
The microbiota is capable of digesting many plant compounds which we cannot to produce short chain fatty acids
These can signal the colonic epithelium where they act as the main energy source, result in less oxidative DNA damage, regulate proliferation, maintenance of barrier function, tumour suppression and cytokine production
They can also signal the immune system to allow an enhanced ROS burst, cause more phagocytosis, induction of apopotosis, modulate recruitment and cause cytokine production
What is the effect of omega-3 fatty acids on immune cells?
There is less recruitment
Lower proinflammatory cytokine production
And this is associated with an anti-diabetic phenotype
What is the connection between the microbiota provided by GPR43 signalling and immune cell functions?
This is a chemoattractant receptor which can be triggered by microbiota produced SCFA