Lec 18 - The human microbiome and disease

Question 1

List the 5 factors influencing microbial community composition and provide example/s of each

Answer 1

1. Environmental parameters eg pH and temp
2. Interactions between microbes eg competition
3. Rapid evolution and speciation eg horizontal gene transfer
4. Stochastic/unpredictable forces eg where baby is born
5. Hysteresis = physical property lags behind changes ie takes time for the environmental change to change the microbiome

Question 2

List the 7 determinants of the gut microbiome

Answer 2

1. Birthing process
2. Infant feeding method
3. Stress
4. Diet
5. Pharmaceuticals and xenobiotics
6. Geography
7. Lifecycle stages

Question 3

Why is diet so important with determining the gut microbiome?

Answer 3

• Bacteria more metabolically diverse than humans
• Change in diet alters microbiota
• Ancestral diet

Question 4

What were the aims and findings of the human microbiome project?

Answer 4

Aim = finding core microbiome of humans
Findings:
- Each habitat had small number of highly abundant conserved taxa
- Relative abundance varied but generally present
- Variability stable but changed with diet and antibiotics

Question 5

Why is it important to change the microbiome early in life?

Answer 5

• Microbiota develops long-term stability (succession) after 2-3yrs = hard to change
• Most colonisation after birth

Question 6

What is dysbiosis?

Answer 6

Imbalance in microbial community associated with disease

Question 7

Describe the 3 ways dysbiosis can occur

Answer 7

1. Pathobionts = potential pathogens normally living as symbiont overgrow after trigger
2. Loss of commensals = allows overgrowth of pathobionts
3. Loss of diversity = HIV, diabetes and inflammatory bowel disease associated

Question 8

Describe the upper and lower regions of the human gut and the relative amount of microbes in them

Answer 8

Upper = acidic, high O2 allowing small number of aerobic/facultative anaerobes

Lower = neutral, low O2 allowin anaerobic microbes, has the most microbes

Question 9

List some diseases/conditions associated with dysbiosis

Answer 9

Atherosclerosis, obesity, inflammatory bowel disease, diabetes, liver disease, neurodegeneration, allergies, autoimmunity, metabolic syndromes

Question 10

Compare a healthy and unhealthy diet

Answer 10

Healthy = low animal fat and protein, high plant fibre
Unhealthy = high animal fat and protein, low plant fibre

Question 11

Compare the effects of a healthy vs unhealthy diet on the microbiota

Answer 11

Healthy
- SCFAs = increased mucus, tight junctions
- GLP-1 = appetite regulation, insulin production

Unhealthy
- Sulfate reduction = decreased mucus
- TMAO from red meat = atherosclerosis
- No SCFAs = leakage of PAMPs causing inflammation