The Human Microbiome

Question 1

Normal number of bacteria on skin

Answer 1

10^6/ml

Question 2

Normal number of bacteria in colon

Answer 2

10^12/ml

Question 3

Diversity of phyla in human microbiome

Answer 3

Narrow diversity. Only a few phyla of domain bacteria present.

Question 4

Number of genes in human genome vs microbiome

Answer 4

10^4 vs 10^6 genes

Question 5

Microbiomic digestion aid role

Answer 5

Degrade polysaccharides, make vitamin K

Question 6

Microbiomic aid in development:
1)
2)
3)

Answer 6

1) Help epithelial cells mature
2) Angiogenesis
3) Lymphocyte development

Question 7

Characteristics of majority of commensals

Answer 7

Bacteria, anaerobic

Question 8

Main phyla of commensals:
1)
2)
3)
4)

Answer 8

1) Bacteroidetes
2) Firmicutes
3) Actinobacteria
4) Proteobacteria (relatively rare)

Question 9

Proteobacteria

Answer 9

E. coli

Question 10

Frequency of proteobacteria in microbiome

Answer 10

Relatively rare

Question 11

Main aerobic bacterial commensals

Answer 11

Staphylococcus, streptococcus, lactobacillus

Question 12

Is bacterial community structure stable?

Answer 12

Yes

Only changes at the extremes of life

Question 13

Does microbiome change much between people?

Answer 13

Yes. Under 50% bacterial species shared between twins.

Question 14

Most represented phyla in microbiome

Answer 14

Bacteroidetes, firmicutes

Question 15

TLR expression on enterocytes
1)
2)
3)

Answer 15

1) Apical surface: TLR2, TLR4 weakly expressed
2) Cytoplasm: TLR3, 7, 9 expressed in endosomes
3) Basal surface: TLR5 expressed

Question 16

Microbiomic compound that maintains epithelial integrity

Answer 16

SCFA (short-chain fatty acid)

Question 17

How bacteroidetes avoid TLR binding

Answer 17

Express lipid A variants

Question 18

How commensal bacteria skew adaptive immune system

Answer 18

Skew towards Treg, Th2

Question 19

How pathogenic bacteria skew adaptive immune system

Answer 19

Skew towards Th1, Th17 (inflammatory)

Question 20

Effects of germ-free environment:
1)
2)
3)
4)

Answer 20

1) Low IgA expression
2) Poorly-developed Peyers pathches
3) Few intra-epithelial lymphocytes
4) Prone to allergies (poor Treg, unwanted Th2 differentiation)

Question 21

Specificity of commensal-induced IgA

Answer 21

Cross-reactive with pathogenic species

Question 22

Role of glycocalyx in tolerance

Answer 22

Keeps commensals away from enterocytes.

Pathogenic bacteria can penetrate glycocalyx, therefore are recognised as pathogenic

Question 23

Cytokines secreted in response to commensal bacteria

Answer 23

TGF-beta

Question 24

Cytokines secreted in response to pathogens

Answer 24

IL6, IL12, TGF-beta

Question 25

Disease directly associated with dysbiosis
1)
2)

Answer 25

1) Commensals cause infectious disease

2) Nutritional deficiency (malabsorption, vitamin deficiency)

Question 26

Disease indirectly associated with dysbiosis

Answer 26

1) Obesity
2) Inflammatory bowel syndrome
3) Allergies
4) Autoimmune disorders

Question 27

Disease caused by commensal clostridium difficile

Answer 27

Pseudomembranous colitis

Question 28

Clostridium difficile carrier rate

Answer 28

Around 3% of population

Question 29

Pseudomembranous colitis pathogenesis:
1)
2)
3)

Answer 29

1) Commensal flora altered (often with broad-spectrum antibiotics)
2) C. difficile overgrows in gut
3) Adheres to mucosal epithelium, produces cytotoxin, cell death, inflammation, bowel necrosis

Question 30

Characteristic of microflora associated with repeated clostridium difficile infection

Answer 30

Greatly reduced diversity of flora (by analysis of 16S RNA)

Question 31

GIT commensal infections at extra-intestinal sites.  Common bacteria:
1)
2)
3)
4)

Answer 31

1) E. coli (UTI)
2) Klebsiella sp (wounds)
3) Enterobacteriaciae
4) Bacteroidetes sp.(wounds)

Question 32

Inflammatory bowel disease susceptibility:

1)

Answer 32

1) Genes associated with NOD-like receptors and certain cytokines
2) Also associated with diet, reduced microflora diversity, appendectomy

Question 33

Prebiotics

Answer 33

Dietary supplements that promote growth of commensal bacteria

Question 34

Probiotics

Answer 34

Administration of therapeutic commensal bacteria, EG: lactobacillus

Question 35

Vitamins from commensal bacteria

Answer 35

Vitamin K, biotin (B7), folate (B9)

Question 36

Changes induced in host metabolism by commensals

Answer 36

1) Lipid metabolism

2) Short-chain fatty acid metabolism, associated with maintaining enterocyte function and differentiation

Question 37

Phyla associated with obesity

Answer 37

Higher levels of actinomycetes, firmicutes.

Decrease in bacteroidetes

Question 38

Associations with a high-fat diet

Answer 38

Increase in inflammatory responses, decrease in microflora diversity

Question 39

Severe form of malnutrition

Answer 39

Kwashiorkor

Question 40

Findings of Malawian Kwashiorkor study

Answer 40

1) Gene-content in faeces of Kwashiorkor-affected children fails to develop with age
2) Therapeutic food doesn’t sustain an initial change in gene content
3) Shows association between microflora composition and health

Question 41

Effect of Kwashiorkor microbiota on metabolism

Answer 41

Chemicals produced that selectively inhibit TCA-cycle enzymes
–> Impaired cellular energy metabolism

Question 42

Experimental treatment for Kwashiorkor

Answer 42

Faecal transplant