Lecture 22 Human Microbiome

Question 1

Why are humans considered holobionts?

Answer 1

Due to coexistence and evolution of host and microbial cells.

The term signifies the interconnectedness of the host organism and its associated microbial communities.

Question 2

What are the key events in the development of the human gut microbiome, and how does diet impact it?

Answer 2

Infant inoculation, dominance of bifidobacterium, introduction of solid food

Different diets lead to distinct microbial patterns influencing long term metabolism and weight-gain.

Question 3

How does the gut microbiome prevent infection?

Answer 3

Colonial Resistance
- host microbial outcompete pathogens

Bacterial Interference
-bacteriocins (direct)

Innate Immune system
- indirect response
-always on at low levels

Adaptive immune system
- response to a given stimulus

Antigens
-distinction between foreign and own antigens
-remember previous pathogen from exposure and strengthens its response.

Question 4

What are the direct and indirect mechanisms of the gut microbiome in preventing infection?

Answer 4

Direct mechanisms include bacteriocins and Type 6 secretion system

Indirect mechanisms involve stimulation of the host innate immune system, secondary bile acids, and maintaining low oxygen levels.

Question 5

How does the gut microbiome interact with the immune system, and what role do short-chain fatty acids (SCFAs) play?

Answer 5

Microbiome simulates cytokine production, trains the immune system, and balances pro and anti-inflammatory signals.

SCFAs especially butyrate play a crucial role in stimulating physiological changes, reducing inflammation and regulating immune response

Question 6

What are the associations between the gut microbiome and the brain?

Answer 6

Gut microbiome is associated with neurotransmitter production, influencing mood and serotonin.

gut-brain interaction via the vagus nerve and cognition

Question 7

What are the distinct types of skin microbiota, and how does Staphylococcus epidermis collaborate with the immune system?

Answer 7

dry>moist>sebaceous
decreasing diversity

s.epidermis stimulates…
- AMP production by keratinocytes

-bacterial interference
bacteriocins
* Interferes with quorum sensing of other species of
bacteria

Question 8

How does microbiome development occur in infants, and why is early childhood a sensitive period?

Answer 8

microbiome development depends on environment (vaginal canal and caregivers)

by 3 years old, microbiome is adult-like

sensitive time for developing healthy microbiome that maintains homeostasis

determines the composition of microbiome, fiber is important etc.

Question 9

What dominates the gut microbiome before babies eat solid food?

Answer 9

Bifidobacterium dominates before solid food.

Question 10

List the functions of the gut microbiome

Answer 10

-ferments indigestible foods, -synthesizes micronutrients
-metabolizes toxins
-influences immune system maturation
-regulates intestinal blood supply
-protects against pathogens
-produces essential metabolites like SCFAs

Question 11

What role do short-chain fatty acids (SCFAs) play in the gut microbiome?

Answer 11

SCFAs, including acetate, propionate, and butyrate, are fermentation products that stimulate physiological changes, modulate immune response, and balance pro and anti-inflammatory signals in the gut.

Question 12

What are the chemical defences in the immune system, and how do they contribute to pathogen defense?

Answer 12

Lysozymes - disrupt NAG and NAM crosslink to peptidoglycan

Lactoferrin and transferrin - in tears, milk sweat blood

enzymes producing reactive oxygen species

antimicrobial peptides
Cationic peptides – 3 types, mainly involved in membrane disruption
* Cathelicidins, defensins, histatins

complement system

Question 13

What is dysbiosis?

Answer 13

imbalance of microbiome, contribution of microbiome to disease.

Question 14

What is the first line of defence?

Answer 14

physical, chemical, and mechanical barriers
* Skin
* Mucous, tears & other secretions
* Cilia in respiratory tract
* Stomach acid and peristalsis
* Urine

Question 15

What are the 5 key phyla that make up the human microbiome?

Answer 15

Actinobacteria
Fusobacteria
Bacteroidetes
Firmicutes
Proteobacteria

Question 16

Obese people tend to have more of which bacteria?

Answer 16

more Firmicutes than Bacteroidetes

• Results in the production of more acetate which is absorbed more readily by
  liver cells and converted to lipids /fats

Question 17

Gut microbiome functions

Answer 17

1. Ferment foods
2. Synthesize micronutrients like vitamins
3. Metabolize toxins, carcinogens and other compounds (e.g. cholesterol)
4. Ensure immune system maturation
5. Impact maturation of gut lining (i.e. colonocytes)
6. Regulate intestinal blood supply
7. Protect against enteric pathogens
8. Produce metabolites that serve important functions in the body
9. Secondary bile acids, butyrate etc.

Question 17

What do SCFA’s do?

Answer 17

stimulate cytokine
stimulate T regulatory cells
butyrate inhibits pro-inflammatory cytokine production

• C-type lectins that kill Gram positive pathogens are stimulated by SCFAs
• Butyrate stimulates oxygen consumption by host colonocytes, resulting in
  lower oxygen in gut which inhibits aerobic pathogens

Question 17

How does eating fiber benefit your microbiome?

Answer 17

Increase short chain fatty acids (SCFAs) production

• C2 – acetate; C3 – propionate; C4 - butyrate

-propionate reduces cholesterol synthesis

-butyrate feeds colonocytes and stimulates intestinal hormones that surpress hunger.

Question 17

Gut microbiome and immune system

(bile acids, germ-free hosts, MAMPs)

Answer 17

Gut microbes play a role in converting and activating bile acids. This process contributes to reducing inflammation and preventing the growth of pathogens in the gut.
Antimicrobial Peptides in Germ-Free Hosts:

Germ-free hosts, which lack a normal gut microbiome, produce lower amounts of antimicrobial peptides. These peptides are essential for defending against microbial invaders.
MAMPs and Cytokine Production:

Microbe-Associated Molecular Patterns (MAMPs) from the gut microbiome interact with host immune cells, triggering the production of cytokines. Cytokines are signaling molecules that regulate immune responses.