The Microbiota of the GIT Flashcards
1
Q
Where is the start of the GIT?
A
Mouth
2
Q
Where does the GIT run to?
A
Rectum/anal canal
3
Q
What is the transit time in the mouth?
A
1 min
4
Q
What is the transit time in the oesophagus?
A
4-8sec
5
Q
What is the transit time in the stomach?
A
2-4hr
6
Q
What is the transit time in the small intestine?
A
3-5hr
7
Q
What is the transit time in the colon?
A
10hr-several days
8
Q
What does transit time affect?
A
- Bacterial populations due to different bacterial growth rates
- Intestinal cell exposure to toxins consumed with food or produced by bacteria
9
Q
What happens to the size of bacterial populations as you go down the GIT?
A
Increase
10
Q
Why doe bacteria populations increase in size as you go down the GIT?
A
- Increasingly anaerobic conditions
- Increasing bacterial density
- Increasing dominance of obligate anaerobes
11
Q
Bacterial population size in stomach?
A
10^3-10^4/ml
12
Q
Bacterial population size in small intestine?
A
10^8/ml
13
Q
Bacterial population size in colon?
A
10^10-10^11/ml
14
Q
Anaerobic
A
Living in the absence of air
15
Q
Aerobic
A
Living in the presence of air
16
Q
Facultative anaerobic bacteria
A
- Can grow in the presence of air
- Can grow in the absence of air
17
Q
Obligate anaerobe
A
- Cannot grow in the presence of oxygen
- Many rapidly killed in the presence of oxygen
18
Q
What happens to the dominant bacteria along the GIT?
A
Change
19
Q
Why do the dominant bacteria change along the GIT?
A
Due to different:
- Oxygen concentrations
- pH
- Transit times
20
Q
What happens to the pH along the GIT?
A
- Mouth pH 6.5>7.5
- Stomach pH 1.4>4
- Duodenum pH 7>8.5
- Distal ileum pH 4>7
- Colon pH 5.5>6.5
21
Q
What do the large numbers of bacteria mean?
A
- There are more microbial than human cells in the body
- These microbes are important for out health and what we eat can impact their activities
- The average human adult will poop their own body weight in bacteria every 1-2 years
22
Q
What are the taxonomy and bacterial classifications in order from generic to specific?
A
- Life
- Domain
- Kingdom
- Phylum
- Class
- Order
- Family
- Genus
- Species
23
Q
What is the bacterial diversity od the large intestine?
A
- 4 major phyla
- > 200 genera
- > 1250 species
24
Q
At what level do meaningful comparisons have to be made?
A
Genus level
25
How do bacteria act together?
In a population/consortium
26
What is important to maintain health?
A diverse microbiota
27
What do different bacteria do?
Perform different functions
28
What are the vast majority of the resident bacteria in the GIT beneficial for?
Health
29
What does the GIT microbiota do?
- Defence against pathogens
- Modification of host secretions
- Metabolism of dietary components
- production of essential metabolites to maintain health
- Development of immune system
- Host signalling
30
What does healthy gut microbiota lead to?
Healthy person
31
How does GIT microbiota defend against pathogens?
- Competition
- Barrier function
- pH inhibition
32
Why does junk food not feed our gut microbes?
Energy absorbed in stomach/small intestine
33
Where doe GIT microbes grow?
On the fibre we eat in foods like fruit, vegetables, pulses and whole grains and convert it into thousands of different products
34
What can GIT microbe also use for growth?
Endogenous (host-derived) substrates
35
What similarities are there between the small intestine and large intestine?
- Gut lumen
- Epithelial surface
- Goblet cells
- Crypts
- Muscular layer
36
What are the benefits of including dietary fibre in our diet?
- Improves faecal bulking, eases passage, results in shorter transit time
- Contains important phytochemicals, anti-oxidants and vitamins
- Bacterial fermentation
37
What does bacterial fermentation result in?
- Releases additional phytochemicals
- Maintains slightly acidic pH
- Increased commensal bacterial population and pH improves resistance to pathogens
- essential supply of short chain fatty acids
38
What happens in the small intestine?
- Digestion of dietary carbohydrate, starches, sugars, fat, protein
- Absorption of monosaccharides, fat, amino acids, soluble phytochemicals
39
What happens in the large intestine?
- Microbial fermentation of non-digestiable carbohydrates
| - Absorption of SCFA, BCFA, gases, phytochemicals, other metabolites and minerals
40
What is disposed of in faeces?
Undigested carbohydrate, lignin, unabsorbed nutrients
41
What are the 3 main short chain fatty acids?
- Butyrate
- Propionate
- Acetate
42
What does the ratio of SCFA depend on?
- Substrate availability
| - Bacterial composition
43
What is the function of butyrate?
Epithelial cell growth and regeneration
44
What is the function of propionate?
- Gluconeogenesis in the liver
| - Satiety signalling
45
What is the function of acetate?
- Transport in blood to peripheral tissues
| - Lipogenesis
46
Describe the metabolism of gut microbia in the proximal colon.
- Carbohydrate rich
- pH mildly acidic
- Turnover rapid
47
Describe the metabolism of gut microbial in the distal colon.
- Little fermentable carbohydrate
- pH neutral
- Turnover slow
48
What are the major products and gases produced by CHO metabolism?
- Acetate, propionate, butyrate
| - CO2, H2, CH4
49
What are the major products and gases produced by protein metabolism?
- Branched SCFA
| - NH3, H2S
50
What is the link between diet, microbes and health?
- Specific combinations of gut microbes and food are beneficial for our health and others are detrimental
- Many important gut microbial activities are driven by what we eat
51
What does a diverse balanced diet lead to?
- A diverse balanced microbiota
| - Diverse balanced products
52
What are the 2 mechanisms that helps in defence against pathogens?
- Barrier effect
| - Active competitive exclusion
53
What is the barrier effect?
-The large numbers of the indigenous microbiota prevent colonisation by ingested pathogens and inhibit overgrowth of potentially pathogenic bacteria normally resident at low levels
54
What is the active competitive exclusion conferred by?
Both microbe-microbe and microbe-host interactions
55
How do the mucus layers differ in bacterial content?
- Outer layer: contains bacteria
| - Inner layer: normally few bacteria
56
How does the difference in bacterial colonisation between the mucus layers keep the gut health?
The mucus layer forms a barrier between the luminal bacterial population and the epithelial cells
57
Describe the defences against pathogens at each layer.
- Commensal bacteria close to the epithelium black and prevent adhesion/colonisation by pathogens
- Outer mucus layer barrier effect
- Inner mucus layer prevents bacterial penetration
- The few bacterial cells that penetrate through the epithelium are dealt with efficiently by the immune system
58
What does a normal immune response lead to?
Homeostasis
59
What does a dysregulated immune response lead to?
Inflammation
60
Describe pH inhibition.
Generally pathogens grow optimally at pHs over 6
61
Why is there less disease in the proximal colon?
- High substrate concentrations
- High fermentation rates
- High SCFA production and absorption
- Low pH: pathogen exclusion
- Quicker transit: high epithelial cell turnover
62
Why is there more disease at the distal colon?
- Low substrate concentrations
- Low fermentation rates
- Low SCFA production and absorption
- Higher pH: less pathogen exclusion and more protein fermentation
- Slower transit time: higher exposure to harmful compounds
63
What is the largest lymphoid organ in the body?
Gut
64
What is the is the commensal bacteria population of the gut?
10^10-10^11 bacteria/g gut contents
65
What must the gut be able to do from an immune response point of view?
- Respond appropriately to foreign/pathogenic agents
- Actively down regulate immune responses to self proteins, dietary antigens and the commensal microbiota
- Recognise and respond to pathogen invasion
66
Some gut microbiota species are pro-inflammatory while other are ....
Anti-inflammatory
67
What doe pattern recognition receptors do?
Detect and bind different molecules associated with pathogens, microbe or cell components
68
What do Toll like receptors specifically recognise?
Bacterial components
69
What does activation of PRRs trigger?
- Molecular signally cascades
| - Co-ordinated production of pro-inflammatory cytokines, chemokines and co-stimulatory molecules
70
What is inflammation an interplay between?
Pro- and anti-inflammatory cytokines
71
Name a pro-inflammatory cytokine?
IL-6
72
Name an anti-inflammatory cytokine?
IL-10
73
What are TLRs?
- Specific proteins involved in the innate immune system
| - Membrane spanning non-catalytic receptors
74
Where are TLRs expressed?
Epithelial cells like macrophages and dendritic cells
75
What do TLRs recognise?
Microbial molecules that are structurally conserved
76
When do autoimmune diseases occur?
When the immune system can no longer distinguish between harmful detrimental pathogens and the commensal bacteria
77
What can dysbiosis of the gut microbiota lead to?
Disruption of homeostasis leading to gut inflammation
78
SCFA are important signally molecules that impact on...
- Gut health
- Metabolic health
- Brain health
- Overall health
79
What detects SCFA?
Receptors on gut epithelial
80
Name three signals activated by SCFA?
- FFAR2
- FFAR3
- GPR109A
81
What activates FFAR2 and what does it result in?
- Acetate, propionate
| - GLP-1 secretion (inhibits fat accumulation)
82
What activates FFAR3 and what does it result in?
- Propionate, butyrate
| - PYY secretion (improves insulin resistance and satiety signalling to the brain)
83
What activates GPR109A and what does it result in?
- Butyrate
| - Suppresses colonic inflammation and carcinogenesis (anti-inflammatory cytokine )
84
How does microbial composition vary through life?
- Changes
- Baby considerably different to elderly
- Baby dependent on type of feeding
85
What is the greatest influence on our guts microbiota population?
Diet
86
What is the most densely populated body site colonised predominantly by anaerobic bacteria?
Large intestine
87
What do the bacteria in the large intestine ferment and what is the result?
- Dietary fibre
| - the metabolite produced like SCFA are important for health and circulate round the body having effects outside the gut
