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Microbiology BIO-5015B > Lecture 26: Gut microbiome > Flashcards

Lecture 26: Gut microbiome Flashcards

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1
Q

What is meant by “hidden deficiency”

A

“The wrong mic of gut bacteria, not just starvation, could contribute to severe malnutrition”

In Malawi, 10s of thousands of children have this, with 15% being fatal

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2
Q

What is the gut microbiome?

A

~3000 bacterial species in gut. Also contains yeast fungi (“mycobiome”) and viruses (“virome”). The “bacteriome” makes up >99% of the microbiome

what is the bacteriology of different regions of the human gastrointestinal tract:

  1. Small intestine: 10^4-6g
  2. Stomach: 10^3g
  3. Large intestine: 10^12g
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3
Q

What are the three ‘biomes’ of the gut microbiome?

A
  1. Bacteriome
  2. Mycobiome (fungi)
  3. Virome
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4
Q

What is the gut mycobiome

A 
1. Commensal fungi coexisting with other 
    'bugs'
2. Can be positive or negative
3. Low diversity compared to bacteriome
4. Dominated by yeast, making up 8 of the 
     top 15 most abundant genera
   a. Saccharomyces 
   b. Malassezia
   c. Candida
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5
Q

What is the gut virome

A 
1. Human faeces contain at least 10^9 virus- 
   like particle per gram
2. Highly individualised 
3. Vast majority of viral particles 
    unidentified
4. Viruses important to them carrying 
    antibiotic resistance genes as well as 
    virulence genes
5. Can modulate the microbiome 
    composition
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6
Q

What are the major groups of bacteria in the gut?

A
  1. Firmicutes. E.g;
    a. Lactobacillus
    b. Clostridium
    c. Staphylococcus etc
  2. Bacteroidetes. E.g;
    a. Bacteroides
    b. Prevotella
  3. Proteobacteria. E.g;
    a. Escherichia
    b. Pseudomonas
  4. Actinobacteria. E.g;
    a. Bifidobacterium

90% of gut = Firmicutes and Bacteroidetes

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7
Q

What is meant by the evolution of microbiomes?

A

Different animals have unique microbiomes.

These include:

  1. Persissodactyla:
    a. Elephant
    b. Rhino
    c. Horse
    d. Zebra
  2. Primates:
    a. Monkeys
    b. Chimpanzees
  3. Carnivora:
    a. Lions
    b. Hyena
  4. Artiodactyla:
    a. Sheep
    b. Cow
    c. Giraffe
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8
Q

How does he gut microbiome develop with age?

A 
1. Vaginally delivered infants - 
   microbiota is dominated by mothers 
   vaginal and faecal bacteria
2. C-section infants - microbiota 
    dominated by skin and bacteria from 
    hospital environment (LESS 
    MICROBIOTA DIVERSITY THAN 
    VAGINAL)
3. Microbiota changes with weaning
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9
Q

What factors affect the gut microbiome?

A
  1. Genetics
  2. Ageing
  3. Diet
  4. Stress
  5. Infection
  6. Antibiotics
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10
Q

What are the beneficial and harmful effects of the gut microbiome?

A

Beneficial:

  1. Stim of host immune system
  2. aids digestion
  3. Prod short chain FAs and vitamins
  4. Inhibition of pathogenic bacteria
  5. Transformation of bioactive compounds
  6. Provide fixed nitrogen

Harmful:

  1. Prod of carcinogens
  2. Role in obesity and diabetes
  3. Involvement in inflammatory diseases
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11
Q

What makes up the mutualistic relationship between microbes and humans

A
  1. Microbiome provides health benefits
  2. We provide a home:
    a. free food
    b. free water
    c. constant temperature
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12
Q

What role does the microbiome have in health and disease?

A
  1. Pathogen exclusion
  2. Brain development
  3. biotransformation of dietary components
  4. asthma
  5. cancer
  6. liver function
  7. obesity
  8. diabetes
  9. mucosal immunity
  10. inflammatory bowel disease
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13
Q

What are the molecular approaches to characterising microbial communities?

A
  1. Microbial community. From:
    a. GI tract
    b. Seawater
    c. biofilm
    d. soil
  2. DNA isolation
  3. Sequence all bacterial DNA
    (“metagenomic” shotgun sequencing) OR
    PCR variable region of genome - 16S
    rRNA (“metataxonomic”)
  4. Next gen sequencing
  5. Bioinformatics
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14
Q

What is the microbiome variance between individuals?

A
  1. > 50% of humans share 75 species
  2. > 90% of humans share 57 species

“GREATER SIMILARITY BETWEEN INDIVIDUALS ON A FUNCTIONAL LEVEL”

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15
Q

What is ulcerative colitis (UC)?

A
  1. Form of inflammatory bowel disease (IBD)
  2. Specifically in large intestine
  3. 1/1000 un UK and western world affected

Different factors include:

a. Genetics
b. Environmental
c. Gut bacteria

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16
Q

What is the relationship between the gut microbiome and obesity?

A
  1. 64% of Americans overweight or obese
  2. Factors affecting obesity:
    a. high calorie intake
    b. genetic predisposition
    c. Microbial metabolism
17
Q

What did a study find regarding the relationship between the microbiome and obesity in mice?

A

“Obese mice have 50% less Bacteroidetes (major phyla in gut microbiome) than lean mice, the reverse is true for Firmicutes”

CAUSE OR EFFECT???

Another study transplanted the gut microbiome from an obese mice into a normal mice. This lead to a greater percentage increase in total body fat compared to donation of microbiota from lean donors.

18
Q

What is the role of the gut microbiome in nitrogen fixation?

A
  1. new species found in human stool:
    “D. diazotrophicus sp. nov”
  2. Ability to fix nitrogen (N2 to NH3 via
    nifHDK) may be an advantage in survival
    in complex gut microbiome if nitrogen
    becomes limited particularly in
    people with low protein diet
19
Q

What is the role of C. difficile in humans for biocontrol of gut pathogens

A 
1. A superbug-major cause of hospital 
   acquired infections
2. Spores can persist in the hospital 
    environment: hands, floor, clothing, 
    bedding
3. Produce toxins
4. Possible food borne pathogen
5. 20,000 cases of CDI ("Closridium 
    difficile infection") in UK
20
Q

What is Clostridium difficile infection (CDI)

A
  1. Mild = severe diarrhoea, abdominal
    pain, fever
  2. Severe = bowel inflammation (1500
    deaths in UK)
  3. Elderly patients who have taken broad
    spectrum antibiotics and immuno-
    compromised patients are at most risk
    (>80% of CDI reported in people >65 YO)
  4. Clear association between disruption
    of normal gut biota by antibiotic
21
Q

How is CDI treated?

A
  1. Currently treatable via:
    a. Metronidazole
    b. oral vancomycin
  2. Relapse occurs 20-30%
  3. Potential risk of antibiotic resistance
22
Q

What is FMT (faecal transplant)?

A
  1. Treatment for CDI
  2. Procedure:
    a. patient stops taking antibiotics
    b. patient given enema to empty the
    bowels
    c. Nasjejunal (NJ) tube is inserted through
    by gastroenterologist
    d. Fresh faecal slurry is prepared
    e. Transported to hospital and delivered
    to patient via NJ tube
    f. Takes 20 minutes
  3. 92% success rate in norwich
23
Q

Pros and cons of FMT treatment for CDI

A

+ Cheap
+ high success rate
+ Easy to administer
+ Very few side effects

  • Risk transferring unknown pathogens
  • Public acceptance
  • Long-term impact of foreign microbiome
    unknown
24
Q

What is the future of FMT developments?

A
  1. Frozen donor faecal matter
  2. Freeze dried donor faecal capsules
  3. Defined mix of gut bacteria instead of
    whole faecal microbiome
25
Q

How does the gut microbiome affect brain function and behaviour?

A
  1. Gut microbiome associated with:
    a. anxiety
    b. depression
    c. sensitivity to pain
    d. serotonin production
    e. autism
26
Q

What did a study on mice find after a faecal transplant in mice regarding the gut-brain axis?

A 
1. Recipient mice would take up 
   personality of donor
2. daring mice would become 
    apprehensive
3. timid mice would become more 
    exploratory
4. FMT using aged donors lead to 
    impaired spatial learning and memory 
    in young adult recipients
27
Q

What is the gut brain axis?

A
  1. The guts mind
  2. “enteric nervous system”
  3. Gut produces more serotonin than the
    brain

Microbiology BIO-5015B (30 decks)

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