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Gastrointestinal > Intro to Gut Microbiology > Flashcards

Intro to Gut Microbiology Flashcards

1
Q

What is the normal flora of the gut?

A

Flora normally present in all surfaces and mostly (99%) in the gut

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2
Q

What is meant by resident flora?

A

commensal organisms that are there for life

microbial melting pot

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3
Q

What is transient flora?

A

temporarily reduced, carried or changed due to environmental factors
- not permanent flora

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4
Q

Give an example where the flora changes in the body

A

organisms in baby’s gut change during weaning
e.g. baby to adult - weaning
Bifidobacterium (>90% of the flora) and utilises breast milk (gram +ve)
diet; environment; stress; hormones; age; transit time causes change from bifiobacterium →adult microbiota

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5
Q

Explain how baby faecal transition occurs

A
  1. Sterile meconium (first time baby
    defecates; green coloured)
  2. facultative anaerobes (baby acquires
    microbial flora)
  3. Strictly anaerobic gut (O₂ free environment
    in colon)
  4. Bifidobacterium
  5. After weaned off milk microbes change to
    adult-like gut microbiota (bacteroides)
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6
Q

Describe the biological features of bifidobacterium

A

Gram +ve Rod; branched

Produce lactic acid; prevent growth of G-ve bacteria that may try colonising baby’s gut

Metabolises breast milk → nutrients for baby and energy for itself

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7
Q

Describe the transition of bacteria when acquiring adult microbial flora

A

Weaning:
Bifidobacterium → bacteroides, clostridia & eubacteria (adult-like gut microbiota) anaerobic organisms living in lower half of colon

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8
Q

What is commensal flora?

A

one organism derives food or other benefits from another organism without hurting or helping it

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9
Q

Which part of the normal flora is commensal

A

No one species of gut flora is a commensal, but together the flora may be regarded as commensal (no harm to host)

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10
Q

What is the significance of the normal flora?

A

A combination of organisms produces normal flora allowing normal physiology of gut

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11
Q

Describe the distribution of bacteria in the gut

A

Bacteria distributed throughout GI Tract
Fewer in stomach due to high Acidity
More complex and larger mixture of bacteria as we progress through duodenum & ileum (esp. Terminal ileum)

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12
Q

Describe the flora in the colon

A

Colon: anaerobic environment, contains facultative and obligate anaerobes
Very large amount of complex mixtures of bacteria
E.g. bacteroides, clostridia, E.coli

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13
Q

How does disease affect the gut flora

A

Microbiome alterations (dysbiosis) are associated with disease states

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14
Q

How does Inflammatory Bowel Disease affect the distribution of bacteria?

A

In patients with inflammatory bowel disease, the distribution of bacteria is very different
Generalised diversity changes and species differ

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15
Q

What can cause gut flora dysbiosis?

A 
Crohn’s disease
Inflammatory bowel disease – ulcerative colitis
Irritable bowel syndrome – IBS
Clostridium difficile  
Colon Cancer
Allergy
Celiac disease (gluten)
Diabetes – type I and II
Obesity  (Bacteroidetes/Firmicute ratios)
Mental health and depression
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16
Q

How can we test faeces microbiota?

A

Take a DNA extraction, sequencing one of the genes encoded in bacterial genome that encodes for the 16s ribosomal RNA

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17
Q

What structural defences are present in the gut?

A

Seamless epithelium, tight junctions; High turnover

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18
Q

Describe the mechanical host defences of the gut

A

Peristalsis, chewing, fluid movement through gut, prevents pathogens adhering to gut

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19
Q

What biochemical defences are in the gut?

A

Gastric acid, bile, mucous are highly toxic to bacteria

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20
Q

What are the immunological defences of the gut?

A

Secretory IgA in lumen of mucosal surfaces binds to bacteria preventing epithelial binding, intraepithelial lymphocytes

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21
Q

What issues can be caused by microbes in the gut?

A

Spread of infections to the body

damage of barriers; pH change; overgrowth, AIDS

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22
Q

What are the benefits of the gut flora?

A
  • Colonisation Resistance
  • Metabolites produced of benefit to host
  • Normal development of immunity
  • Aids digestion
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23
Q

How is colonisation resistance beneficial to the gut?

A
  • blocks pathogens
  • gut full of commensals = hard for pathogens to get in,
    reproduce & cause disease
  • Hard because niche taken up by commensals
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24
Q

What beneficial metabolites are produced in

A

Vit K, B12, organic acids
Enhanced utilisation of amino acids
Butyrate for colonocytes – maintain anaerobiosis

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25
Q

What is the effect of normal immunity development?

A

Increases tolerance; antigenic stimulation, Tregs, IL17

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26
Q

How does the gut flora aid digestion?

A

Fermentation of sugars (10% of energy released from colon);

Gas? H2 or methane; regulation of fat storage

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27
Q

What are probiotics?

A

organisms we think will contribute to a healthy biome

28
Q

What are the functions of the probiotics?

A

Best probiotics produce lactic and organic acids
~10% absorbable energy from dietary fibre;
↑ diversity of polysaccharides for metabolism

29
Q

Give examples of probiotics

A

Lactobacillus acidophilus,
Bifidobacteria - B.longum,
Bacteroides thetaiotaomicron
Some Streptococci

30
Q

What are the clinical uses of probiotics?

A

Control of diarrhoea in infants
Relieve constipation
Improve digestion of lactose

31
Q

What are prebiotics?

A

nutrients that alter the gut ecosystem

32
Q

What is the role of prebiotics?

A

Encourage good microbes to grow e.g. breast milk - ‘bifidus factor’
certain oligosaccharides
e.g. fructooligosaccharides

fermented in colon by probiotic organisms
promotes growth of probiotes

33
Q

What is a bacteriocin?

A

a protein produced by bacteria of one strain and active against those of a closely related strain

34
Q

What is microbial antagonism?

A

When some organisms inhibit growth of other organism to limit growth of competitors and pathogens
e.g. bacteriocins

35
Q

What causes a loss of flora?

A

bacterial / pathogen overgrowth

36
Q

What disrupts the normal flora the most?

A

Certain antibiotics (e.g. ciprofloxacin) disrupt our microbiome more than others

37
Q

What is the consequence of loss of flora due to antibiotics?

A

Leads to antibiotic associated colitis
as antibiotics reduce no. of gut flora and changed it => lead to overgrowth of clostridium difficile = pseudomembranous colitis

38
Q

What is colitis?

A

inflammation of colon caused by introduction of antibiotics

39
Q

Outline the effects of microbial antagonism

A
  • Limits growth of competitors + pathogens
  • Bacteriocins
  • Reduced no. of available epithelial receptors
  • Keeps pH low
  • Controls oxidative potential (anaerobic growth)
  • Limits pathogen growth
  • Occupy all niches
  • High numbers
  • Waste products
40
Q

What is gastroenteritis?

A

Acute syndrome characterised by generalised GI symptoms in any combination including:

  • Nausea
  • Vomiting
  • Diarrhoea
  • Abdominal discomfort
41
Q

What is diarrhoea?

A

Watery / liquid stools, usually with an increase in stool weight above 200 g per day and an increase in daily stool frequency and often a sense of urgency

42
Q

What are the clinical consequences of diarrhoea?

A
  • severe dehydration, excessive fluid and electrolyte loss,
    hypovolaemia; hypokalaemia; organ failure
  • long-term morbidity and reduced growth
43
Q

What is dysentery?

A

Inflammatory disorder of GI Tract, usually large intestine; often associated with blood & pus (as penetrated natural barrier). As well as pain, fever and abdominal cramps

44
Q

What is enterocolitis?

A

Inflammation involving mucosa of small and large intestine e.g. Crohn’s Disease

45
Q

What is the impact of diarrhoeal diseases?

A

Many deaths a year (2 million)

Especially under 5’s (undergo multiple episodes a year) -> massive global health burdens (it is preventable)

46
Q

What are the main causes of diarrhoeal diseases?

A

Infectious mciroorganisms e.g.

  • Bacteria
  • Viruses
  • Parasites - protozoal and worms
47
Q

How are diarrhoeal diseases spread?

A

infectious micro organisms shed in faeces and spread to new host (faecal-oral route)

48
Q

What are the characteristic patterns of gut infections?

A

Acute watery diarrhoea
Dysentery = Acute / chronic diarrhoea + blood + pus
Poor Fat absorption = chronic diarrhoea / malabsorption
Infective proctitis : ano-rectal STIs

49
Q

Which pathogen is responsible for travellers diarrhoea?

A

normally e. Coli

50
Q

Explain how food poisoning occurs

A

Diarrhoea from eating food containing toxins or bacteria in food that grow inside us and produce toxins

51
Q

Which patients are classed as immunocompromised hosts?

A
  • AIDS patietnts
  • immunosuppressed
  • elderly or very young
52
Q

What causes antibiotic related diarrhoea?

A

altered normal flora

53
Q

What damage is caused by an infection of the GI tract?

A

Pharmacological
- action of bacterial toxins local or distant to site of
infection e.g. cholera

Local inflammation

  • in response to superficial microbial invasion
    e. g. Shigella dysentery or Campylobacter food-poisoning

Deep invasion
- to blood and lymphatics and dissemination of the
organism to other body sites – enteric fevers e.g.
Typhoid fever or Hepatitis A

Perforation/ulceration
- of mucosal epithelium peritonitis; intra-abdominal
abscess (e.g. Entamoeba)

54
Q

What are the different mechanisms of diarrhoea?

A

Bacterial Toxins
Adherence
Penetration + invasion

55
Q

Describe how bacterial toxins cause diarrhoea?

A
  • Enterotoxins are toxins that affect the gut
  • Exotoxins effect fluid/electrolyte transport by increasing
    / decreasing cAMP
  • Cytotoxins direct cell damage
56
Q

How does pathogen adherence cause diarrhoea?

A

e.g. E. coli EPEC enteropathogenic adhere to cells below and damage epithelium

57
Q

Explain how invasion and penetration by pathogens can lead to diarrhoeal disease

A

Disruption of tissue architecture and function
- enteroinvasive
Inflammation

58
Q

What is the function of villus in the gut?

A

Main function is absorption

59
Q

What is the role of crypts in the gut?

A

Mainly secretion

60
Q

What are heat stable toxins?

A

Toxins that are not destroyed even when heated. If consumed, effects will prevail

61
Q

What are heat liable toxins?

A

Heat-liable toxins are inactivated through cooking

62
Q

Outline the mechanism of action of toxins in the villi causing diarrhoeal diseases

A

Affect electrolyte channels in the enterocytes by:
Heat labile toxin stimulate AC, causing cAMP to disregulate protein kinase → changes Cl- channel causing electrolyte imbalance and thus fluid balance
Similar with GC

63
Q

Explain how mucosal injury can lead to diarrhoea

A

Virus / bacteria can penetrate into villi resulting in villous atrophy. There’s no absorptive capacity = anti-absorptive diarrhoea (malabsorption)

64
Q

Why does damage to gut mucosal surface cause diarrhoea?

A

=> immediately get crypt hyperplasia to try replace villus; crypt tries to regenerate villus. At this time you get lots of secretion, so combination of atrophy and then high secretion = anti-absorptive diarrhoea, eventually recovering (takes up to 3 days)

65
Q

What viruses cause gut disorders?

A
  • Astrovirus (star)
  • Calicivirus (Star of David)
  • Rotavirus (wheel)
  • Poliovirus (featureless)
  • Norwalk SRSVs) Norovirus (ill defined lace-like
    appearance)
66
Q

Which properties of intestnal physiology are affected by the microbiome?

A
  • Energy balance regulation + pathophysiology of obesity
  • Modulates digestion + absorption
  • ↑ energy harvesting
  • Microbiome influenced by diet, antibiotics, surgery +
    genes
  • Microbiome contributes to host metabolism + energy
    homeostasis beyond nutritional processing e.g.
    endocrine function and inflammatory signals

Gastrointestinal (18 decks)

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