Lecture 14 - Microbiome 1 Flashcards
Where are microbes found on the body?
Which area has the most?
Gut - the most
Vagina
Skin
Throat
Why are microbiota important?
Associated with:
• Health
• Disease
What is the Human Microbiome?
Project to sequence all of the genes associated with the microbiota
Compare the bacteria at the different colonisation sites in the body?
Different phyla, depending on the location
How many phyla are represented in the human microbiota?
Only a few
What is meant by ‘humans are superorganisms’?
Humans have evolved to collaborate with microbiota, giving us properties that we would not have on our own
What are the general benefits of microbiota?
- Enhanced digestion
- Intestinal deelopment
- Protection
How do commensals aid digestion?
Degrade polysaccharides
Vitamin K
How do commensals aid development of our gut?
Epithelial cell maturation
Angiogenesis
Lymphocyte development
How do commensal protect us from pathogens?
- Occupy a niche
- Competition for nutrients
- Stimulate the immune system
What are the main phyla found in the microbiome?
Bacteroidetes
Firmicutes
Actinobacteria
Which phylum is only rarely found in the microbiome?
Proteobacteria (E. coli)
Which is the most common phylum in the gut?
Firmicutes
Which phylum commonly colonises the skin?
Actinobacteria
Are most of the bacterial phyla represented in the human microbiome?
No - relatively few phyla are found in the human microbiome
Describe the distribution of bacteria within the gut
More bacteria as we progress down the GIT
Describe the changes in the microbiome over one’s lifetime
When we are healthy, are microbiome is stable
At the extremities of life, our microbiome can be unstable
What factors influence the microbiome?
- Age
- Diet
- Mode of delivery during childbirth
- Breast feeding
- Antibiotics
What is the effect of fever on the human microbiome?
Changes the makeup of the microbiome
Increase in number of actinobacteria
Over the first 2.5 years of life, what brings about the major changes in the microbiota in the gut?
The introduction of solid foods into the diet
Onset of Bacteroidetes
Compare microbiota in twins
Monozygotic twins: less than 50%
Unrelated people: even less
What is the greatest site of antigenic challenge in the body?
The gut
Where do microbiota sit in the gut?
Above the mucin and glycocalyx
How does the microbiota help the innate immune system?
Direct:
• Produce antimicrobials
Indirect
• Interact with PRRs to induce tolerogenic responses
• Produce compounds that maintain the epithelium
Does the microbiota bring about inflammation?
We call it physiological inflammation
What does the interaction of microbiota with PRRs brings about?
- Induction of regulatory cytokines
* Induction of antibacterial compounds, defensins
How does the gut epitehlium distinguish between invading pathogens and gut commensals?
Proximity:
• gut commensals are held at arms length
• pathogens bind tightly to the gut epithelium
PRRs:
• PRRs detect invasion on basolateral surface
• Commensals bind poorly to PRRs
Compare the types of Th induced by commensals and pathogens
Commensals: Treg, Th2 (tolerogenic)
Pathogens: Th17, Th1 (inflammatory)
What is the effect of commensals of DCs?
- Induce tolerogenic Th cells
* Indues more effective sampling by the DCs
What are the effects of the microflora on the adaptive immune system?
How do we know this?
- less IgA
- poorly developed Peyer’s Patches
- fewer IELs
- more susceptible to infection
- prone to allergies
We know this from studies of Germ-free mice
What is the effect of commensals on IgA?
Why is this good?
• Induce low levels of IgA
IgA cross reacts with pathogens
What is a term for physiological inflammation?
Mucosal homeostasis
Which cytokine is really important for mucosal homeostasis?
What does it do?
TGF-beta
It is really important for skewing towards Treg and Th2
What is it called when the makeup of the intestinal microbiota is altered?
Dysbiosis
How is dysbiosis directly associated with disease?
- infectious disease due to gut microbiota
* nutritional (malabsorption)
What are the indirect assocations of dysbiosis with disease?
- Obesity (metabolic syndromes)
- Inflammatory bowel disease
- Allergies
- Autoimmune diseases
What is a common cause of dysbiosis?
Antibiotic use
Describe the expression of PRRs on the gut epithelium
Why is this so?
Apical: low expression
In endosomes: TLR 3, 7, 9
Basolateral: TLR 5
Don’t want to have much of a response to commensals in the gut
We only want to have a response if bacteria penetrate further
