The Microbiota of the GIT Flashcards

1
Q

Where is the start of the GIT?

A

Mouth

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2
Q

Where does the GIT run to?

A

Rectum/anal canal

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3
Q

What is the transit time in the mouth?

A

1 min

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4
Q

What is the transit time in the oesophagus?

A

4-8sec

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5
Q

What is the transit time in the stomach?

A

2-4hr

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6
Q

What is the transit time in the small intestine?

A

3-5hr

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7
Q

What is the transit time in the colon?

A

10hr-several days

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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
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9
Q

What happens to the size of bacterial populations as you go down the GIT?

A

Increase

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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
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11
Q

Bacterial population size in stomach?

A

10^3-10^4/ml

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12
Q

Bacterial population size in small intestine?

A

10^8/ml

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13
Q

Bacterial population size in colon?

A

10^10-10^11/ml

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14
Q

Anaerobic

A

Living in the absence of air

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15
Q

Aerobic

A

Living in the presence of air

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16
Q

Facultative anaerobic bacteria

A
  • Can grow in the presence of air

- Can grow in the absence of air

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17
Q

Obligate anaerobe

A
  • Cannot grow in the presence of oxygen

- Many rapidly killed in the presence of oxygen

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18
Q

What happens to the dominant bacteria along the GIT?

A

Change

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19
Q

Why do the dominant bacteria change along the GIT?

A

Due to different:

  • Oxygen concentrations
  • pH
  • Transit times
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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
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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
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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
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23
Q

What is the bacterial diversity od the large intestine?

A
  • 4 major phyla
  • > 200 genera
  • > 1250 species
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24
Q

At what level do meaningful comparisons have to be made?

A

Genus level

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25
Q

How do bacteria act together?

A

In a population/consortium

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26
Q

What is important to maintain health?

A

A diverse microbiota

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27
Q

What do different bacteria do?

A

Perform different functions

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28
Q

What are the vast majority of the resident bacteria in the GIT beneficial for?

A

Health

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29
Q

What does the GIT microbiota do?

A
  • Defence against pathogens
  • Modification of host secretions
  • Metabolism of dietary components
  • production of essential metabolites to maintain health
  • Development of immune system
  • Host signalling
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30
Q

What does healthy gut microbiota lead to?

A

Healthy person

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31
Q

How does GIT microbiota defend against pathogens?

A
  • Competition
  • Barrier function
  • pH inhibition
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32
Q

Why does junk food not feed our gut microbes?

A

Energy absorbed in stomach/small intestine

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33
Q

Where doe GIT microbes grow?

A

On the fibre we eat in foods like fruit, vegetables, pulses and whole grains and convert it into thousands of different products

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34
Q

What can GIT microbe also use for growth?

A

Endogenous (host-derived) substrates

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35
Q

What similarities are there between the small intestine and large intestine?

A
  • Gut lumen
  • Epithelial surface
  • Goblet cells
  • Crypts
  • Muscular layer
36
Q

What are the benefits of including dietary fibre in our diet?

A
  • Improves faecal bulking, eases passage, results in shorter transit time
  • Contains important phytochemicals, anti-oxidants and vitamins
  • Bacterial fermentation
37
Q

What does bacterial fermentation result in?

A
  • 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
Q

What happens in the small intestine?

A
  • Digestion of dietary carbohydrate, starches, sugars, fat, protein
  • Absorption of monosaccharides, fat, amino acids, soluble phytochemicals
39
Q

What happens in the large intestine?

A
  • Microbial fermentation of non-digestiable carbohydrates

- Absorption of SCFA, BCFA, gases, phytochemicals, other metabolites and minerals

40
Q

What is disposed of in faeces?

A

Undigested carbohydrate, lignin, unabsorbed nutrients

41
Q

What are the 3 main short chain fatty acids?

A
  • Butyrate
  • Propionate
  • Acetate
42
Q

What does the ratio of SCFA depend on?

A
  • Substrate availability

- Bacterial composition

43
Q

What is the function of butyrate?

A

Epithelial cell growth and regeneration

44
Q

What is the function of propionate?

A
  • Gluconeogenesis in the liver

- Satiety signalling

45
Q

What is the function of acetate?

A
  • Transport in blood to peripheral tissues

- Lipogenesis

46
Q

Describe the metabolism of gut microbia in the proximal colon.

A
  • Carbohydrate rich
  • pH mildly acidic
  • Turnover rapid
47
Q

Describe the metabolism of gut microbial in the distal colon.

A
  • Little fermentable carbohydrate
  • pH neutral
  • Turnover slow
48
Q

What are the major products and gases produced by CHO metabolism?

A
  • Acetate, propionate, butyrate

- CO2, H2, CH4

49
Q

What are the major products and gases produced by protein metabolism?

A
  • Branched SCFA

- NH3, H2S

50
Q

What is the link between diet, microbes and health?

A
  • 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
Q

What does a diverse balanced diet lead to?

A
  • A diverse balanced microbiota

- Diverse balanced products

52
Q

What are the 2 mechanisms that helps in defence against pathogens?

A
  • Barrier effect

- Active competitive exclusion

53
Q

What is the barrier effect?

A

-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
Q

What is the active competitive exclusion conferred by?

A

Both microbe-microbe and microbe-host interactions

55
Q

How do the mucus layers differ in bacterial content?

A
  • Outer layer: contains bacteria

- Inner layer: normally few bacteria

56
Q

How does the difference in bacterial colonisation between the mucus layers keep the gut health?

A

The mucus layer forms a barrier between the luminal bacterial population and the epithelial cells

57
Q

Describe the defences against pathogens at each layer.

A
  • 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
Q

What does a normal immune response lead to?

A

Homeostasis

59
Q

What does a dysregulated immune response lead to?

A

Inflammation

60
Q

Describe pH inhibition.

A

Generally pathogens grow optimally at pHs over 6

61
Q

Why is there less disease in the proximal colon?

A
  • High substrate concentrations
  • High fermentation rates
  • High SCFA production and absorption
  • Low pH: pathogen exclusion
  • Quicker transit: high epithelial cell turnover
62
Q

Why is there more disease at the distal colon?

A
  • 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
Q

What is the largest lymphoid organ in the body?

A

Gut

64
Q

What is the is the commensal bacteria population of the gut?

A

10^10-10^11 bacteria/g gut contents

65
Q

What must the gut be able to do from an immune response point of view?

A
  • 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
Q

Some gut microbiota species are pro-inflammatory while other are ….

A

Anti-inflammatory

67
Q

What doe pattern recognition receptors do?

A

Detect and bind different molecules associated with pathogens, microbe or cell components

68
Q

What do Toll like receptors specifically recognise?

A

Bacterial components

69
Q

What does activation of PRRs trigger?

A
  • Molecular signally cascades

- Co-ordinated production of pro-inflammatory cytokines, chemokines and co-stimulatory molecules

70
Q

What is inflammation an interplay between?

A

Pro- and anti-inflammatory cytokines

71
Q

Name a pro-inflammatory cytokine?

A

IL-6

72
Q

Name an anti-inflammatory cytokine?

A

IL-10

73
Q

What are TLRs?

A
  • Specific proteins involved in the innate immune system

- Membrane spanning non-catalytic receptors

74
Q

Where are TLRs expressed?

A

Epithelial cells like macrophages and dendritic cells

75
Q

What do TLRs recognise?

A

Microbial molecules that are structurally conserved

76
Q

When do autoimmune diseases occur?

A

When the immune system can no longer distinguish between harmful detrimental pathogens and the commensal bacteria

77
Q

What can dysbiosis of the gut microbiota lead to?

A

Disruption of homeostasis leading to gut inflammation

78
Q

SCFA are important signally molecules that impact on…

A
  • Gut health
  • Metabolic health
  • Brain health
  • Overall health
79
Q

What detects SCFA?

A

Receptors on gut epithelial

80
Q

Name three signals activated by SCFA?

A
  • FFAR2
  • FFAR3
  • GPR109A
81
Q

What activates FFAR2 and what does it result in?

A
  • Acetate, propionate

- GLP-1 secretion (inhibits fat accumulation)

82
Q

What activates FFAR3 and what does it result in?

A
  • Propionate, butyrate

- PYY secretion (improves insulin resistance and satiety signalling to the brain)

83
Q

What activates GPR109A and what does it result in?

A
  • Butyrate

- Suppresses colonic inflammation and carcinogenesis (anti-inflammatory cytokine )

84
Q

How does microbial composition vary through life?

A
  • Changes
  • Baby considerably different to elderly
  • Baby dependent on type of feeding
85
Q

What is the greatest influence on our guts microbiota population?

A

Diet

86
Q

What is the most densely populated body site colonised predominantly by anaerobic bacteria?

A

Large intestine

87
Q

What do the bacteria in the large intestine ferment and what is the result?

A
  • Dietary fibre

- the metabolite produced like SCFA are important for health and circulate round the body having effects outside the gut