Microbiota of the GI tract Flashcards

1
Q

how does trinity time change along the GI tract

A
increases:
mouth - 1 min
oesphagus - 4-8 secs
stomach - 2-4 hr
small intestine - 3-5 hr
colon/large intestine - 10 hr to severla days
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2
Q

what does transit time effect

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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3
Q

what happens to bacterial populations as you travel along the GI tract from mouth to rectum

A

increasingly anaerobic (due to anaerobic conditions)

increasing bacterial density (stomach = 10(3)-10(4)/ml)
(small intestine = 10(8)/ml)
(colon/large intestine = 10(10)-10(11)ml)

increasing dominance of obligate anaerobes

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4
Q

define anaerobic

A

living in the absence of air

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5
Q

define aerobic

A

living in the presence of air

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6
Q

define facultative anaerobic bacteria

A

can go in the presence of oxygen AND in the absence of oxygen
(although some may prow poorly)

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7
Q

define obligate anaerobic bacteria

A

cannot grow in the presence of oxygen - many rapidly killed in the presence of oxygen (i.e. would therefore not be found in the mouth)

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8
Q

give some factors that can affect what bacteria is dominant at different points in the GIT

A

oxygen concentration
different pH
different transit time

eg stomach - pH1.5-4 and mixed O2 = facultative anaerobes

eg colon - pH 5.5-6.5 and no O2 = obligate anaerobes

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9
Q

at what level of classification are meaningful comparisons done between bacteria types

A

at the genus level

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10
Q

what are some of the functions of GIT microbiota

A

metabolism of dietary components

production of essential metabolites to maintain health

development of immune system - immune priming

host signalling - gut-brain axis

defence against pathogens - competition, barrier function, pH inhibition

modifications of host secretions (mucin, bile, gut receptors, etc)

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11
Q

what components of our diet do GIT microbes grow on

A

fibre from fruit, vegetables, pulses, whole grains - microbes convert it into thousands of different products

can also use endogenous (host derived) substrates for growth

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12
Q

what are the benefits of having fibre in your diet

A

health protection - improves faecal bulking, eases passage, results in shorter transit times

contains important phytochemicals, antioxidants and vitamins

bacterial fermentation

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13
Q

what does bacterial fermentation of fibre 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

converts non-ingestible carbohydrates and residual proteins into short/branched chain fatty acids, gases, phytochemical, minerals, other metabolites

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14
Q

what are the three main short chain fatty acids and what are their functions

A

ratio 1:1:3 (depends in substrate availability AND bacterial composition)

butyrate - epithelial cell growth and regeneration

propionate - gluconeogenesis in the liver and satiety signalling

acetate - transported in blood to peripheral tissues for lipogenesis

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15
Q

what are the major products of carbohydrate metabolism by the GIT microbiota

A
  1. short chain fatty acids - acetate, propionate, butyrate

2. gases - CO2, H2, CH4

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16
Q

what are the major products of protein metabolism by the GIT microbiota

A
  1. branched short chain fatty acids - iso-butyrate, isovalerate
  2. gases - NH3, H2S
  3. phenols, indoles, amines
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17
Q

different bacteria produce different metabolites - give some examples

A

firmicutes - polysaccharide utilisation = butyrate production

actinomycetes - utilise prebiotics = lactate production

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18
Q

how does the GIT bacteria defend against pathogens

A
  • colonisation resistance
  • pH inhibition
  • gut mucosal immune system
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19
Q

what are the 2 methods of colonisation resistance and describe briefly how they work

A
  1. barrier effect - uses mucous layers and large number of indigenous bacteria prevent colonisation by ingested proteins AND inhibit overgrowth of potentially pathogenic bacteria normally resident at low levels
  2. active competition exclusion - conferred by both microbe-microbe and microbe-host interactions
20
Q

how does the mucous layer help keep the gut healthy

A

2 mucous layers - outer and inner
outer - contains bacteria, barrier affect
inner - normally only few bacteria, prevents bacterial penetration

forms barrier between luminal bacterial populations and epithelial cells

commensal bacteria close to epithelium block and prevent adhesion/colonisation by pathogens

the few bacterial cells that penetrate through the epithelium are dealt with by the immune system

21
Q

what can happen if the mucus layer barrier is disrupted

A

bacterial cells penetrate the mucus layer and the epithelial barrier - causes a dysregulated immune response and inflammation

22
Q

at what pH do pathogens generally go best at

A

pH >6

23
Q

where is more likely to get disease from pathogens - the proximal or distal colon

A

distal colon more prone to disease that proximal colon

24
Q

why is the distal colon more prone to disease from pathogens

A
  • high pH so less pathogen exclusion

- more protein fermentation - slower transit therefore higher exposure to harmful compounds

25
Q

why is the proximal colon less prone to disease from pathogens

A
  • low pH so more pathogen exclusion

- quicker transit therefore high epithelial cell turnover

26
Q

what is the relationship between the gut microbiota and the gut immune system

A

co-evolve:

microbiota shapes the development of the immune system, and the immune system in turn shapes the composition of the microbiota.

27
Q

what must the gut immune system be able to do

A
  1. respond appropriately to foreign/pathogenic agents
  2. actively down-regulate immune responses to ‘self’ proteins, dietary antigens and the commensal microbiota
  3. Recognise and respond to pathogen invasion
28
Q

how does the postnatal immune system differ from the prenatal immune system

A

prenatal immune system immature - postnatal “learns” from bacterial exposure

29
Q

how does the host detect bacteria that does penetrate into the gut epithelium

A

innate immune system

uses pattern recognition receptors - detect and bind different molecules associated with pathogens, microbes or cell components

30
Q

what type of PRR specifically recognise bacterial components

A

Toll Like receptors

31
Q

what does the activation of PRRs trigger

A

molecular signalling cascades

  • coordinate production of pro-inflammatory and anti-inflammatory cytokines, cheekiness and co-stimulatory molecules
32
Q

what is inflammation and interplay between

A

pro-inflammatory and anti-inflammatory cytokines

33
Q

give examples of some PRO-inflammatory cytokines

A

**IL-6

IL-1, TNF, IFN-g, IL-12

34
Q

give examples of some ANTI-inflammatory cytokines

A

**IL-10

IL-18, IL-4, IL-13, IFN-a, TGF-B

35
Q

what are toll like receptors

A

specific proteins involved in the inmate immune system that recognise microbial molecules that are structurally conserved

**different TLRs specifically recognise different bacterial components

36
Q

what is the structure of toll like receptors

A

membrane spanning, non-catalytic receptors

expressed in epithelial cells like macrophages and dendritic cells

37
Q

what can happen if TLRs have inappropriate responses

A

because the ability to distinguish “self” from foreign pathogens depend on TLRs - inappropriate responses are linked to some autoimmune diseases

38
Q

why is homeostasis of the gut microbiota and the host immune system important

A

essential to maintain host health - autoimmune diseases can occur when the immune system can no longer distinguish between harmful pathogens and commensal bacteria

39
Q

what is dysbiosis and what can it cause

A

microbial imbalance - can disrupt homeostasis and lead to inflammation

40
Q

what are short chain fatty acids important as

A

signalling molecules

41
Q

what SCFA signalling molecules inhibit fat accumulation

A

acetate, propionate (and butyrate)

result in GLP-1 secretion which inhibits fat accumulation

42
Q

what SCFA signalling molecules improve insulin resistance and satiety signalling to the brain

A

propionate and butyrate

results in PYY secretion

43
Q

what SCFA signalling molecules suppress colonic inflammation and carcinogenesis

A

butyrate

results in the release of anti-inflammatory cytokines e.g. IL-10

44
Q

what happens to microbial composition throughout life

A

changes throughout life - not fixed

45
Q

what factors influence the different microbiota we have throughout life

A

**dietary changes - greatest influence

birth - natural, Cs, preterm

feeding - breastfed, formula, mixed

weaning - age, pureed/solid foods, diversity of foods

diet expansion

diet maintenance - afad diets, poor food choices, alcohol

diet contraction - inability ot no desire to eat certain foods

46
Q

give some examples of the microbial diversity throughout life and if it is good or bad

A

breastfed infant - low diversity = good

healthy adult - high diversity = good

frail elderly - low diversity = bad