Lecture 10: changes in gut functioning and anatomy Flashcards
Renewal + tight junctions impaired during ageing
ok
In X hallmarks of ageing, gut plays a role
all
Name some age-related health issues related to impaired GI functioning
Oral problems, decreased GI barrier function, changes in microbiota, malabsorption, decreased oesophageal motility
What can be the cause of clostridium difficile infections in elderly?
PPI
Ageing + gut-brain axis. What are age-related disruptions?
- 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
Where, in the villus or crypt, ar CBC stem cells and paneth cells located? Where are the other cells?
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)
What happens during ageing with the absorptive and secretory cells?
During ageing:
* less differentiation into absorption
* more differentiation into secretory cells.
(important)
What are (gut) organoids ? characteristics?
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
What is a leaky gut?
- Impaired gut barrier (decreased barrier function bc of tight juctions)
Pathogenic bacteria can enter (also in the blood)
What factors can play a role in damaging the barrier functioning of the gut?
- Nanoparticles
- Food additives
- Detergents
- Microplastics
- Airborne allergens protease activity
- Stress
What happens to the mucus layer during ageing?
becomes smaller
Measuring GI barrier function: how can this be done?
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.
Immune response of the big molecules passing the gut is dependent on the exercise intensity.
ok
Examples of receptors that recognize nutrients and metabolites, including those generated by the microbiota in the GI tract?
- ‘taste’ receptors
- Olfactory receptors
- Toll-like
- Bile acid
What happens to these receptors during ageing?
Loss of receptors during ageing
Results in reduced nutrient-uptake (protein, Ch, vit D, ..)
Research is lacking
What determines a healthy microbiota?
- resistance (ability to resist pertubations)
- resilience (ability to return to baseline)
- microbial richness and diversity
- presence/absence of specific genera
- functionality/metabolic parameters
During ageing, there are important shifts in microbiota Mention them
(beta- and alfa-)diversity = lower and microbiota is less stable.
Alfa diversity = species diversity. Beta diversity = difference between two people.
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
1 oxytocin (made by lactobacillus reuteri)
2 GABA (made by lactobacillus rhamnosus)
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
1 BDNF, made by bifidobacterium
2 4-EPS (bacteroides)
3 SCFA (SCFA-producing bact)
What is SIBO (Small intestinal bacterial overgrowth )? What does it contribute to?
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
One of the most common causes of death due to bacterial infection in elderly = ?
clostridium difficile
What are cl diff risk factors?
- recent stay hospital/nursing home
- antibiotic
- weak immune syst
- old age
- previous history of cl diff
Chronic low-grade inflammation (metaflammation): vicious cycle
Explain?
- Increase inflammatory tone
- More permeability
- Keeps inflammation going on
Chronic low-grade inflammation is linked to what types of diseases?
It is linked to various pathologies, such as CVD, cancer, depression, auto-immune diseases, neurodegenerative diseases, immunosenescence,IT also conrtibutes to sickness behaviour.
Mice with overexpression ApoE4 = Alzheimer-like model, were triggered by.. and got alzheimer
- Completely sterile mice got no Alzheimer (microbiota was a trigger)
- Conventionally raised mice got Alzheimer
If you have gut problems (obstipation), you increase your chances on ..
Parkinson’s
