Lecture 14 - Microbiome 1

Question 1

Where are microbes found on the body?

Which area has the most?

Answer 1

Gut - the most
Vagina
Skin
Throat

Question 2

Why are microbiota important?

Answer 2

Associated with:
• Health
• Disease

Question 3

What is the Human Microbiome?

Answer 3

Project to sequence all of the genes associated with the microbiota

Question 4

Compare the bacteria at the different colonisation sites in the body?

Answer 4

Different phyla, depending on the location

Question 5

How many phyla are represented in the human microbiota?

Answer 5

Only a few

Question 6

What is meant by ‘humans are superorganisms’?

Answer 6

Humans have evolved to collaborate with microbiota, giving us properties that we would not have on our own

Question 7

What are the general benefits of microbiota?

Answer 7

• Enhanced digestion
• Intestinal deelopment
• Protection

Question 8

How do commensals aid digestion?

Answer 8

Degrade polysaccharides

Vitamin K

Question 9

How do commensals aid development of our gut?

Answer 9

Epithelial cell maturation
Angiogenesis
Lymphocyte development

Question 10

How do commensal protect us from pathogens?

Answer 10

• Occupy a niche
• Competition for nutrients
• Stimulate the immune system

Question 11

What are the main phyla found in the microbiome?

Answer 11

Bacteroidetes
Firmicutes
Actinobacteria

Question 12

Which phylum is only rarely found in the microbiome?

Answer 12

Proteobacteria (E. coli)

Question 13

Which is the most common phylum in the gut?

Answer 13

Firmicutes

Question 14

Which phylum commonly colonises the skin?

Answer 14

Actinobacteria

Question 15

Are most of the bacterial phyla represented in the human microbiome?

Answer 15

No - relatively few phyla are found in the human microbiome

Question 16

Describe the distribution of bacteria within the gut

Answer 16

More bacteria as we progress down the GIT

Question 17

Describe the changes in the microbiome over one’s lifetime

Answer 17

When we are healthy, are microbiome is stable

At the extremities of life, our microbiome can be unstable

Question 18

What factors influence the microbiome?

Answer 18

• Age
• Diet
• Mode of delivery during childbirth
• Breast feeding
• Antibiotics

Question 19

What is the effect of fever on the human microbiome?

Answer 19

Changes the makeup of the microbiome

Increase in number of actinobacteria

Question 20

Over the first 2.5 years of life, what brings about the major changes in the microbiota in the gut?

Answer 20

The introduction of solid foods into the diet

Onset of Bacteroidetes

Question 21

Compare microbiota in twins

Answer 21

Monozygotic twins: less than 50%

Unrelated people: even less

Question 22

What is the greatest site of antigenic challenge in the body?

Answer 22

The gut

Question 23

Where do microbiota sit in the gut?

Answer 23

Above the mucin and glycocalyx

Question 24

How does the microbiota help the innate immune system?

Answer 24

Direct:
• Produce antimicrobials

Indirect
• Interact with PRRs to induce tolerogenic responses
• Produce compounds that maintain the epithelium

Question 25

Does the microbiota bring about inflammation?

Answer 25

We call it physiological inflammation

Question 26

What does the interaction of microbiota with PRRs brings about?

Answer 26

* Induction of regulatory cytokines | * Induction of antibacterial compounds, defensins

Question 27

How does the gut epitehlium distinguish between invading pathogens and gut commensals?

Answer 27

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

Question 28

Compare the types of Th induced by commensals and pathogens

Answer 28

Commensals: Treg, Th2 (tolerogenic) Pathogens: Th17, Th1 (inflammatory)

Question 29

What is the effect of commensals of DCs?

Answer 29

* Induce tolerogenic Th cells | * Indues more effective sampling by the DCs

Question 30

What are the effects of the microflora on the adaptive immune system? How do we know this?

Answer 30

* 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

Question 31

What is the effect of commensals on IgA? | Why is this good?

Answer 31

• Induce low levels of IgA IgA cross reacts with pathogens

Question 32

What is a term for physiological inflammation?

Answer 32

Mucosal homeostasis

Question 33

Which cytokine is really important for mucosal homeostasis? | What does it do?

Answer 33

TGF-beta It is really important for skewing towards Treg and Th2

Question 34

What is it called when the makeup of the intestinal microbiota is altered?

Answer 34

Dysbiosis

Question 35

How is dysbiosis directly associated with disease?

Answer 35

* infectious disease due to gut microbiota | * nutritional (malabsorption)

Question 36

What are the indirect assocations of dysbiosis with disease?

Answer 36

* Obesity (metabolic syndromes) * Inflammatory bowel disease * Allergies * Autoimmune diseases

Question 37

What is a common cause of dysbiosis?

Answer 37

Antibiotic use

Question 38

Describe the expression of PRRs on the gut epithelium Why is this so?

Answer 38

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