Lecture 10: changes in gut functioning and anatomy

Question 1

Renewal + tight junctions impaired during ageing

Answer 1

ok

Question 2

In X hallmarks of ageing, gut plays a role

Answer 2

all

Question 3

Name some age-related health issues related to impaired GI functioning

Answer 3

Oral problems, decreased GI barrier function, changes in microbiota, malabsorption, decreased oesophageal motility

Question 4

What can be the cause of clostridium difficile infections in elderly?

Answer 4

PPI

Question 5

Ageing + gut-brain axis. What are age-related disruptions?

Answer 5

• Mucus layer degraded
• Infiltration bacteria, increased inflammation markers, disrupted immune cell function (neuro-inflammation: Alzheimers etc, see image p41)
• Decreased SCFA important for gut cells, but also brain

Question 6

Where, in the villus or crypt, ar CBC stem cells and paneth cells located? Where are the other cells?

Answer 6

In the crypt niche (at the bottom).
On top of that comes the TA cells, which differnetiate into all other kinds of cells (goblet, EE, enterocytes)

Question 7

What happens during ageing with the absorptive and secretory cells?

Answer 7

During ageing:
* less differentiation into absorption
* more differentiation into secretory cells.
(important)

Question 8

What are (gut) organoids ? characteristics?

Answer 8

little guts
To study the gut

• contain more cells compared to cell cultures
• Complex in vitro system
• Also organoids from brain, lungs
• Can study diseases such as cancer, but also the effect of nutrients

Question 9

What is a leaky gut?

Answer 9

• Impaired gut barrier (decreased barrier function bc of tight juctions)

Pathogenic bacteria can enter (also in the blood)

Question 10

What factors can play a role in damaging the barrier functioning of the gut?

Answer 10

• Nanoparticles
• Food additives
• Detergents
• Microplastics
• Airborne allergens protease activity
• Stress

Question 11

What happens to the mucus layer during ageing?

Answer 11

becomes smaller

Question 12

Measuring GI barrier function: how can this be done?

Answer 12

by physical exercise stress test

Exercise: hypoxia induced.
Give protein peanuts. After exercise (Stress), there is an increased uptake of big molecules.

After exercise (stress) you see the protein peanut (Ara h6). Not in passive state.

Question 13

Immune response of the big molecules passing the gut is dependent on the exercise intensity.

Answer 13

ok

Question 14

Examples of receptors that recognize nutrients and metabolites, including those generated by the microbiota in the GI tract?

Answer 14

• ‘taste’ receptors
• Olfactory receptors
• Toll-like
• Bile acid

Question 15

What happens to these receptors during ageing?

Answer 15

 Loss of receptors during ageing
 Results in reduced nutrient-uptake (protein, Ch, vit D, ..)
 Research is lacking

Question 16

What determines a healthy microbiota?

Answer 16

• resistance (ability to resist pertubations)
• resilience (ability to return to baseline)
• microbial richness and diversity
• presence/absence of specific genera
• functionality/metabolic parameters

Question 17

During ageing, there are important shifts in microbiota Mention them

Answer 17

(beta- and alfa-)diversity = lower and microbiota is less stable.

Alfa diversity = species diversity. Beta diversity = difference between two people.

Question 18

Gut microbiome releases molecules, used by your nervous system (brain).
1 regulates neuronal plasticity (more social behaviour)
2 decreases stress responsiveness, anxiety and depressive-like behaviour

Answer 18

1 oxytocin (made by lactobacillus reuteri)
2 GABA (made by lactobacillus rhamnosus)

Question 19

1 decreases anxiety-like and depressive behaviour via the vagus nerve
2 decreases anxiety-like behaviour, repetitive behaviour and increases communication
3 reduces stress responsiveness and anxiety-like and depressive behaviour

Answer 19

1 BDNF, made by bifidobacterium
2 4-EPS (bacteroides)
3 SCFA (SCFA-producing bact)

Question 20

What is SIBO (Small intestinal bacterial overgrowth )? What does it contribute to?

Answer 20

Presence of bacteria in increased numbers in the small bowel, resulting in excessive fermentation, inflammation or malabsorption
Contributes to micronutrient deficiencies

(Vitamin A, B12, iron..), because the bacteria eat them

Question 21

One of the most common causes of death due to bacterial infection in elderly = ?

Answer 21

clostridium difficile

Question 22

What are cl diff risk factors?

Answer 22

• recent stay hospital/nursing home
• antibiotic
• weak immune syst
• old age
• previous history of cl diff

Question 23

Chronic low-grade inflammation (metaflammation): vicious cycle
Explain?

Answer 23

1. Increase inflammatory tone
2. More permeability
3. Keeps inflammation going on

Question 24

Chronic low-grade inflammation is linked to what types of diseases?

Answer 24

It is linked to various pathologies, such as CVD, cancer, depression, auto-immune diseases, neurodegenerative diseases, immunosenescence,IT also conrtibutes to sickness behaviour.

Question 25

Mice with overexpression ApoE4 = Alzheimer-like model, were triggered by.. and got alzheimer

Answer 25

• Completely sterile mice got no Alzheimer (microbiota was a trigger)
• Conventionally raised mice got Alzheimer

Question 26

If you have gut problems (obstipation), you increase your chances on ..

Answer 26

Parkinson’s