Microbiota Flashcards

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1
Q

What is the definition of microbiota?

A

“Assemblage of microorganisms present in a defined environment”

*most things can be considered to have their own microbiota  e.g. soil will have its own defined microbial community (all unique)

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2
Q

What is the definition of human microbiota?

A

“The total microbial community that resides both on and within us”

*total microbial community ON and IN the host. Every human has their own microbiota (oral cavity, gut, skin etc)

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3
Q

What does the number of bacterial cells depend on?

A

Number depends on how recently you have been to the toilet (majority of bacterial cells reside in the colon)

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4
Q

Are there more bacterial cells or human cells?

A

Bacterial cells outnumber human cells but not by that much

1.3 : 1

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5
Q

What is the Sterile womb hypothesis?

A
  • suggests we are sterile prior to birth (womb is sterile unless there is a complication)
  • Acquisition occurs during birth - vaginal delivery is exposed to lactobacilli
  • C section bypasses vaginal delivery – exposed to surgical and human skin microorganisms
  • This gives slightly different microbiotas depending on route of birth
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6
Q

What is the alternative theory to the sterile womb hypothesis?

A
  • In utero colonisation
  • theory that the womb is not sterile and that it is colonised with gram negative bacteria
  • Based on identification of ‘DNA’ from placenta and amniotic fluid

*although evidence is lacking

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7
Q

When does the development of the microbiota reach a peak?

A

Develops over time and reaches a climax community at around 3yrs old

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8
Q

What does the development of the microbiota depend on?

A
  • Environment e.g. how much sun skin is exposed to
  • Diet (breast milk or formula, weaning? Breast milk and formula nutrients are very similar but cannot mimic all the several hundred different types of bacteria I breast milk that colonises within the child drinking it)
  • Antibiotic exposure in infancy?
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9
Q

Is microbiota the same for any 2 people?

A

NO - everyone has a slightly different one

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10
Q

Where does most bacteria reside in the human body?

A

The large bowel

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11
Q

What are 5 parts of the large bowel?

A
  1. Caecum
  2. Ascending
  3. Transverse
  4. Descending
  5. Rectum
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12
Q

What does the microbiota act as?

A

microbiota acts as a metabolic organ. Activities contribute to health and can also cause disease

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13
Q

What are the 2 most important bacteria when talking about gut communities?

A

Firmicutes and Bacteroidetes (phylums)

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14
Q

How will Eastern vs western populations have different gut communities?

A

Different diets

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15
Q

What is Firmicutes and what does it mean?

A
  • Firmicutes – means ‘strong cell wall’ and it is a phylum
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16
Q

What is Staphylococcus and what does it mean?

A
  • Genus

- Staphylococcus’ meaning grape like coccus (in ancient Greek)

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17
Q

What is aureus and what does it mean?

A
  • Species

- aureus

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18
Q

What are the 3 roles of the gut microbiota in health?

A
  1. Induction of intestinal angiogenesis
  2. Colonisation resistance
  3. Metabolism of carbohydrates and proteins
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19
Q

What happens during the induction of intestinal angiogenesis?

A
  • development of villus capillary network
  • very complicated
  • bacterium induces angiogenesis
  • Bacteroides thetaiotaomicron
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20
Q

What occurs during colonisation resistance?

A
  • Microbiota in the body takes up all free available space to colonise – this limits the space for pathogens that want to adhere to space and produce toxins
  • Second route: microbiota is using up all the free nutrients for a supply of energy – less going round for potential pathogens
  • Microbiota may change the pH by producing organic acids and make the environment unfavourable to pathogens
  • A barrier to potential pathogens
  • Production of antimicrobials
21
Q

What happens during the metabolism of carbohydrates and proteins?

A
  • Fermentation of non-digestible carbohydrates (cellulose, resistant starch, inulin) –> microbiota breaks these down in the later stages of the gut
  • Fermentation product from breaking down these non-digestible carbs are gas and short chain fatty acids (e.g.) butyrate, propionate, acetate
  • Diet provides nutrients for host and the residing microbiota
22
Q

What can the short chain fatty acids produced during fermentation be used as?

A

Can be used as an energy source for the cells lining the colon, but also known to have anti-carcinogenic and anti-inflammatory properties

23
Q

What was the difference between obese and lean phenotypes in mice?

A
  • Lean phenotype was more balanced to fermicutes
  • When put on the same diet, and the Obese phenotype lost weight, microbiota started to become more similar
  • Mice eat their own poo, so if they’re in a mixed cage, the obese phenotype will be consuming the lean phenotypes poo  colonising itself with bacteroidities – started to alter the metabolic profile to lean
  • By increasing bacteroidites, you see a reduction in food consumption (due to altered microbiota)

*Feeding fat mouse skinny poo makes it skinny
Feeding skinny mouse fat poo makes it fat

24
Q

What leads to a reduction in weight in humans?

A
  • increase dietary fibre
  • introducing short chain fatty acids
  • Inulin is broken down by bacteria present in the lower part of gut
25
Q

Does microbiota influence host response to drug?

A
  • YES
  • Bacteria in the body are able to interact with non-antibiotic drugs in the body and alter the response via enzymatic alteration
  • Enzymatic alteration of drug structure may affect toxicity, bioavailability or bioactivity

e.g. Levodopa in the treatment for parkinson’s disease: bacteria residing in the gut which can generate the decarboxylase enzyme and mediate the same activation of drug. Drug was being converted to active dopamine form before crossing BBB – this is where side effects were seen. Less drug availability and cardiac side effects

26
Q

What does dysbiosis mean?

A
  • dysbiosis is an imbalance (perturbation) in what you would consider to be the normal microbiota e.g. any environmental stress
  • May involve bloom of potential pathogens
  • Loss of commensal microbiota
  • Loss of bacterial diversity
27
Q

What may the loss of commensal microbiota lead to? (dysbiosis)

A
  • Loss of commensal microbiota may lead to disease, such as Clostridium difficile associated diarrhoea
28
Q

What is the cause of fatal enterocolitis in hamsters?

A

Clostridium difficile

29
Q

C.diff characteristics?

A
  • gram positive rods
  • spore forming, contains itself using spores in an oxygen environment for a long time without any issues – goes into a dormant-like state
  • obligate anaerobe (doesn’t like oxygen), suited to living in intestine
30
Q

Explain C.diff’s reservoir?

A
  • gut commensal: 3% adults, 75% infants

- environmental (soil)

31
Q

Is c.diff easy to isolate and grow?

A

NO - very difficult

32
Q

What is the major identifiable cause of antibiotic associated diarrhoea?

A
  • dysbiosis of the gut microbiota and CDAD (C.diff associated diarrhoea)
33
Q

What are the clinical manifestations of Dysbiosis of the gut microbiota and CDAD?

A
  • mild to severe diarrhoea

- May lead to pseudomembranous colitis which may lead to toxic mega colon

34
Q

What are the main risk factors for Dysbiosis of the gut microbiota and CDAD?

A
  • over 65yrs

- antibiotic consumption (broad spectrum) causing loss of commensal gut microbiota

35
Q

What antibiotics are associated with onset of C.difficile ?

A

Third generation cephalosporins

  • cefotaxime
  • cefixime
  • cefdinir
36
Q

What happens following antibiotic use that disturbs normal gut flora?

A
  • gut microbiota is damaged, ingesting a spore could lead to infection through producing toxins toxins (toxins are essential in producing diarrhoea)
  • From mild diarrhoea to pseudomembranous colitis
  • Environmental contamination of spores&raquo_space; hospital outbreak
37
Q

How does undisturbed microbiota act?

A
  • breaks down structures on the surface, producing sialic acids and short chain fatty acids – can be used as a source of nutrients for all commensal bacteria
  • also taking primary bile acids present and converting them to secondary bile acids which inhibit the growth of c.difficle.
38
Q

How does antibiotic-disturbed microbiota act?

A

c.diff uses nutrients to grow and bile acids are not present which promotes the growth of sp*?

39
Q

Describe the activity of TcdA or TcdB toxin?

A
  • Activity of toxin will be taken up into the host cell and then it targets row and rack and will enzymatically interfere with target and will cause breakdown of cytoskeleton and tight junctions and epithelial integrity
  • Tight junction stops free movement between cell layers – takes away selective barrier when toxin breaks it down
40
Q

Describe activity of binary toxin (CDT)?

A

Binary toxin has a net effect on actin polymerisation, taken up by cell and enzymatically alters the target. Changing the cell shape – causing pertrustions on the surface, making c.diff easier to adhere to surface

41
Q

What is pseudomembranous colitis ?

A
  • inflammation of the colon
  • formation of pseudomembranes
  • Diagnosis via detection of C. diff toxins, although colonoscopy can be employed (rarely!)
42
Q

What are the symptoms of pseudomembranous colitis ?

A
  • diarrhoea
  • abdominal pain
  • fever
43
Q

SIGHT anogram?

A
Suspect that a case is infective 
Isolation
Gloves and aprons
Hand washing
Test stool for toxin

*- Spores are NOT affected by alcohol handwashing – only soap and water

44
Q

What antibiotics are used in mild disease?

A
  • Antibiotic therapy not always necessary in mild cases

- If required - Oral metronidazole (10-14 d); 400 tds

45
Q

What antibiotics are used in moderate disease?

A
  • Oral metronidazole (10-14d) preferred; 400-500 mg tds
46
Q

What antibiotics are used in severe disease?

A
  • oral vancomycin (10-14 d); 125mg qds

- Fidaxomicin now also an option (10d, 200 mg, twice daily)

47
Q

What non-antibiotic strategies are there?

A
  1. Faecal microbiota transplantation (FMT)

2. Probiotics

48
Q

What is Faecal microbiota transplantation (FMT)

?

A
  • Replacement of gut microbiota with a donor sample
  • Success approaching 92% of cases in treatment of rCDI

BUT

  • lacks standardised approach
  • long term health implications need research
49
Q

What are probiotics?

A
  • Probiotics are live microbial suspensions that may confer a health benefit to the host if given in adequate amounts