107 - Gut Microbiota II

Question 1

Activation of mucosal lymphocytes
1
2
3
4

Answer 1

1) Lymphocytes in PP or MLN activated, enter blood circulation.
2) Acquire homing receptors (a4b7 integrin, MAdCAM-1 ligand) and chemokine receptors for lamina propria chemokines.
3) Migrate to lamina propria through high endothelial venules (have a4b7 integrins on endothelium)
4) Activated B cells produce sIgA

Question 2

Predominant T cell subtype in steady state gut mucosa

Answer 2

Treg

Question 3

Proportion of intraepithelial lymphocytes that are gamma/delta

Answer 3

~10%

Question 4

Pattern recognition receptors on enterocytes
1
2
3

Answer 4

1) TLR2 and 4 high at birth, downregulated afterwards
2 )TLR3, 7, 9 in endosomes
3) TLR5 expressed on basolateral surface

Question 5

Effects of mucus layer on gut epithelium
1
2

Answer 5

1) Direct - Block binding sites, produce bacteriocins, etc.

2) Indirect - Interact with PRR

Question 6

Indirect effects of microbiota on mucus, gut epithelium
1
2
3

Answer 6

1) PAMPS/butyrate leads to increased mucin production
2) SCFA inhibit production of production, secretion of inflammatory cytokines (NF-kB)
3) IL-22 produced after PAMP interaction with intraepithelial lymphocytes, NK-22 leads to increased epithelial integrity

Question 7

What does PAMP signalling stimulate in the gut?
1
2
3

Answer 7

1) Proliferation of crypt enterocytes and Paneth cells
2) Release of antimicrobial peptides from these cells
3) Induction of regulatory cytokines (TGFβ, IL-10, etc)

Question 8

MALT structures that develop pre-natally

Answer 8

Peyer’s patches, mesenteric lymph nodes

Question 9

MALT structure that develops post-natally

Answer 9

Isolated lymphoid follicles

Question 10

Example of a severe form of undernutrition

Answer 10

Kwashiokor

Question 11

Kwashiokor study
1
2
3
4
5
6
7

Answer 11

1) Studied effects of gut microbiota on Malawian twin children (particularly deficient in protein)
2) Hypothesised that gut microbiota provided genes for healthy growth and development
3) Prospective longitudinal study, analysis of faecal samples from twins discordant for Kwashiokor
4) Treat both with therapeutic food, compare outcomes.
5) Transplanted faecal microbiota from children into germ-free mice
6) Feed mice normal diet, examine.
7) Treat mice with therapeutic food, examine

Question 12

Outcomes of Kwashiokor study

Answer 12

Twin with Kwashiokor couldn’t maintain changes in gene content of gut microbiome when changed from poor diet to therapeutic diet.

Mice fed with Kwashiokor microbiome lost weight, microbiome changed composition

Question 13

Effect of Kwashiokor diet on metabolism

Answer 13

Inhibition of tri-carboxylic acid cycle (TCA cycle). –> inhibition of cellular energy production

Question 14

What is obesity associated with?

Answer 14

Low-grade inflammation.

Question 15

Low-grade inflammation associated with obesity
1
2
3

Answer 15

• Induction of inflammatory cytokines (TNFα, IL-1β, IL-6,
IL-17)
• Increase in mast cells, T cells and macrophages
• Increase in Tregs in lean subjects

Question 16

Effect of low-grade inflammation on obesity
1
2
3

Answer 16

• The associated pro-inflammatory signalling desensitises
insulin receptor and leptin receptor signalling
• High-fat diet fed mice have elevated gut and plasma LPS
and increased intestinal permeability
• Inflammation in obese mice modified by an increase in
Bifidobacteria (reduce intestinal permeability)

Question 17

Commensal flora that can spread to extra-intestinal areas, cause disease
1
2
3
4
5

Answer 17

Escherichia coli (esp UTI, wounds)
Klebsiella sp (wounds, LRTI)
Other Enterobacteriaciae
Enterococci (VRE)
Bacteroides sp (wounds)

Question 18

What can increase the rick of developing pseudomembranous colitis?

Answer 18

Appendectomy (4x more likely)

Question 19

Proportion of healthy people carrying C difficile

Answer 19

~3%

Question 20

How can C difficile cause disease?

Answer 20

Adheres to mucosal epithelium, toxin production

Question 21

Treatment for C difficile overgrowth

Answer 21

Metronidazole +/- vancomycin

Question 22

Aspect of gut microbiome that characterises patients with recurrent C difficile infections

Answer 22

Reduced diversity of bacterial species

Question 23

Success rate of C difficile treatment with faecal transplantation

Answer 23

91-98%

Question 24

Recent alternative to faecal transplant

Answer 24

Pure culture of 33 bacteria shown to be successful

Question 25

Prebiotics

Answer 25

Dietary supplements that promote beneficial

bacteria

Question 26

Probiotics

Answer 26

Live organism that when ingested in adequate
amounts, exerts a health benefit to the host, typically
lactobacilli, bifidobacteria, non pathogenic yeasts