The human microbiome

Question 1

Why will two people respond differently to the same drug

Answer 1

because of the genes of the microbes they carry

Question 2

How many cells are in a human body (2)

Answer 2

1. Approx 10^12 /kg
2. 80kg = 80 trillion

Question 3

How many bacteria cells are in the human body (human microbiome) (2)

Answer 3

1. Approx 10:1 (bacteria: human cells)
2. 1-2% of total body mass

Question 4

What is the definition of microbiome

Answer 4

The microorganisms in a particular environment (including the body or part of a body)

Question 5

What is the definition of metagenomics

Answer 5

Study of genetic material recovered directly from environmental samples

Question 6

What is the definition of proteomics (3)

Answer 6

1. A branch of biotechnology
2. concerned with applying techniques of molecular biology, biochemistry and genetics
3. to analyse the structure, function and interaction of proteins produced by genes of a particular cell, tissue or organism

Question 7

What is the definition of pharmacogenomics (3)

Answer 7

1. Study of how genes affect a person’s response to drugs.
2. Combines pharmacology (science of drugs) and genomics (study of genes and their functions)
3. to develop safe, effective medicines and doses that will be tailored to a person’s genetic makeup

Question 8

What has metagenomics explored using 300 healthy individuals (5)

Answer 8

1. Nasal passages
2. Oral cavity
3. Skin
4. GI tract
5. Urogenital tract

Question 9

What is the Integrative Human Microbiome Project (iHMP) (3)

Answer 9

1. Established in 2014
2. 2nd phase after the HMP – consists of 3 projects
   
   1. Pregnancy and preterm birth
   2. Inflammatory Bowel Disease – Crohn’s disease and ulcerative colitis
   3. Prediabetes
3. Integrated longitudinal datasets of biological properties from both the microbiome and host

Question 10

How many species does the stomach include

Answer 10

25

Question 11

How many species does the intestine include

Answer 11

500-1000

Question 12

How many species do the mouth, pharynx and respiratory system include

Answer 12

600+

Question 13

How many species does the skin include

Answer 13

1000

Question 14

How many species does the urogenital tract include

Answer 14

60

Question 15

What are the beneficial effects of gut microflora (3)

Answer 15

1. Immunity - Provide a physical barrier to invasive microbes and enhance the functionality of the immune system
2. Vitamins - Synthesise vitamins B & K as well as absorb calcium and iron
3. Metabolism - metabolic activity allows our body to utilise food that would otherwise not be digested

Question 16

What are the harmful effects of gut microflora (3)

Answer 16

1. Obesity - gut bacteria differ significantly in obese patients
2. Inflammation - major role in the development of various inflammatory diseases including IBS and colitis
3. Autism - a link between autism and decreased gut bacterial diversity

Question 17

Diseases linked to the microbiome (15)

Answer 17

1. Acne
2. Antibiotic-associated diarrhoea
3. Asthma/allergies
4. Autism –
5. Autoimmune diseases
6. Cancer
7. Dental cavities
8. Depression and anxiety
9. Diabetes
10. Eczema
11. Gastric ulcers
12. Hardening of the arteries
13. Inflammatory bowel diseases
14. Malnutrition
15. Obesity

Question 18

What is Helicobacter pylori (3)

Answer 18

1. Curved gram-negative rod bacteria
2. Common precursor of gastritis and peptic ulcers
3. Risk factor for gastric carcinoma (cancer)

Question 19

What does Helicobacter pylori do in the body to survive (2)

Answer 19

1. Synthesise urease which produces ammonia that damages the gastric mucosa
2. The ammonia neutralises acid pH which allows the organism to live in the stomach

Question 20

What is Helicobacter pylori treated with (3)

Answer 20

1. Omeprazole
2. Clarithromycin
3. Amoxicillin

Question 21

What structures are in Helicobacter pylori (5)

Answer 21

1. Flagella - mobility & chemotaxis to colonise under mucosa
2. Urease - neutralise gastric acid, gastric mucosal injury by ammonia
3. Lipopolysaccharides - adhere to host cells, inflammation
4. Outer proteins - adhere to host cells
5. Type IV secretion system - pilli-like structure for injection of effectors

Question 22

What do Helicobacter pylori effectors e.g. cagA do (4)

Answer 22

1. Actin remodelling
2. IL-8 induction
3. Inhibit host cell growth
4. Inhibit apoptosis

Question 23

What is the Helicobacter pylori exotoxin (1) and what does it do (1)

Answer 23

1. Vacuolating toxin (vacA)
2. gastric mucosal injury

Question 24

What are the Helicobacter pylori secretory enzymes (3) and what do they do (1)

Answer 24

1. Mucinase
2. Protease
3. Lipase
4. Gastric mucosal injury

Question 25

What are the Helicobacter pylori tests (4)

Answer 25

1. Test for antibodies in the blood 2. Urea breath test 3. Test for antigens in stools 4. Endoscopic biopsies

Question 26

What is Clostridium difficile (5)

Answer 26

1. Gram +ve rods bacteria 2. Anaerobic 3. Spore forming 4. In the human colon 5. pathogenic

Question 27

What are Clostridium difficile infection symptoms in increasing severity (4)

Answer 27

1. Can be asymptomatic 2. Mild diarrhoea 3. Pseudomembranous colitis 4. Toxic megacolon

Question 28

How are C.difficle infections managed and treated with supportive care (5)

Answer 28

1. Symptomatic treatment 2. Electrolytes 3. hydration 4. nutrition 5. Don’t give antiperistaltic agents

Question 29

What may be a risk factor for C.Difficile

Answer 29

PPIs

Question 30

How are mild/moderate C.difficle infections managed and treated with medication

Answer 30

Metronidazole – 400mg tds for 10-14 days

Question 31

What accompanies severe C.Difficile infection (3)

Answer 31

1. temperature over 38.5°C 2. severe colitis 3. white cell count over 15 x 10^9/L

Question 32

How are severe C.difficle infections managed and treated with medication (2)

Answer 32

1. Oral Vancomycin – 125mg qds for 10-14 days 2. Fidaxomicin - 200mg bd

Question 33

What are other ways in which C. difficile infections are treated (2)

Answer 33

1. Probiotics - Live yoghurts 2. Faecal microbiota transplantation (FMT).

Question 34

What is the Public Health England guidance on the management and treatment of CDI (6)

Answer 34

CCGs should ensure that trusts have a multidisciplinary clinical review team consisting of: 1. a microbiologist 2. an infectious diseases or infection prevention and control doctor 3. a gastroenterologist or surgeon 4. a pharmacist 5. a dietician 6. an infection prevention and control nurse.

Question 35

What body area is Lactobacillus associated with (2)

Answer 35

1. Stomach 2. Intestine

Question 36

What body area is Malassezia furfur associated with

Answer 36

Skin

Question 37

What body area is Clostridium associated with

Answer 37

Intestine

Question 38

What body area is Haemophilus spp associated with

Answer 38

Nose

Question 39

What body area is Fusobacterium spp associated with

Answer 39

mouth

Question 40

Gut microbes influences of Pharmacomicrobiomics / Pharmacometabonomics can be categorised into (2)

Answer 40

1. Direct 2. Indirect

Question 41

Gut microbes direct mechanisms: Activation of Drugs – Prodrug Concept (2)

Answer 41

1. Gut microbes can concert prodrugs into active drugs 2. E.g. Sulfasalazine (treats rheumatoid arthritis, UC, Crohn’s disease) is broken down into 5-ASA in the gut.

Question 42

Gut microbes direct mechanisms: Deactivation of Drugs (2)

Answer 42

1. Gut microbes can encode enzymes that detoxify drugs, 2. eg, digoxin is inactivated by the gut residing Actinobacterium **(Gram +ve, anaerobic, non sporulating) *-* Eggerthella lenta

Question 43

Gut microbes direct mechanisms: Direct binding (2)

Answer 43

1. Gut microbes can bind directly with drugs, compromising their bioavailability, 2. eg, levadopa (treat Pakinsons) is converted to dopamine in the gut, preventing it from reaching the brain

Question 44

Gut microbes indirect mechanisms Intermediates (3)

Answer 44

1. Some metabolic pathways share steps between host enzymes and those encoded by gut microbes. 2. Intermediate microbial products can lead to pathogenesis 3. the best known example of this is not a therapeutic drug but a toxin called melamine

Question 45

Gut microbes indirect mechanisms Altered kinetics (3)

Answer 45

1. Gut microbial metabolites compete with drugs for enzyme-binding sites 2. leading to alterations in the drug efficacy or toxicity 3. e.g. paracetamol

Question 46

Gut microbes indirect mechanisms Immune response (2)

Answer 46

1. The gut microbes can impact drug efficacy by stimulating the host immune system, 2. e.g. cyclophosphamide increases gut permeability leading microbes to translocate into the lymph nodes

Question 47

Gut microbes indirect mechanisms Enterohepatic recycling – eg irinotecan

Answer 47

research currently for the treatment of colon cancer by modulating the activity of the microbiome

Question 48

Gut microbes indirect mechanisms gene expression (2)

Answer 48

1. Gut microbes can alter the hepatic expression of key host enzymes involved in drug metabolism, 2. e.g. CYP450 leading to alterations in drug efficacy or toxicity

Question 49

Digoxin activation (4)

Answer 49

1. Inactivated by gut bacterium (reduces digoxin) Eggerthella lenta. 2. Pair of genes (cgr operon) work together to metabolise digoxin 3. Research looks at strategies to manipulate the cgr operon - Blocking E lenta’s action to allow more active digoxin to the heart. 4. Cgr operon is less active in the presence of the amino acid arginine so could give patients a high protein diet (research on mice  led to higher blood digoxin levels