human microbiome Flashcards

1
Q

The microbes we are exposed to may…

A
  • fail to colonize (then die)
  • become short-term residents (live for short time, body prevent it from being long-term)
  • become long-term residents (shape our life history)
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2
Q

Do we have microbes in utero?

A

No! However after birth the residence of TRILLIONS of microbes is normal

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3
Q

Microbial metagenome is much larger than
human genome?

A

True

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4
Q

The presence of microbes in tissues is…

A

NOT normal.

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5
Q

Tight gut barrier

A

mucin layer over tightly joined epithelial cells
* excludes microbes from the underlying tissues of our body
* mucin layer - lubricating barrier

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6
Q

Parasitism

A

Partner 1 benefits - increased growth output for parasite/pathogen
Partner 2 harmed - reduced growth output for ‘host’
Host better without parasite

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7
Q

Commensalism

A

Partner 1 benefits - increased growth output for commensal
Partner 2 neutral - no growth change for host
Host same with/without commensal

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8
Q

Mutualism

A

Partner 1 benefits - increased growth output for mutualist
Partner 2 benefits - improved growth for host
Host needs microbe for optimal fitness

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9
Q

In the absence of Microbes…

A
  • Gut functions are different – reduced digestive capacity
  • Immune functions are different – essentially no adaptive immunity
  • Metabolic regulation is different – altered neuro-endocrine signalling pathways
  • Cognitive functions & mood are different – underdeveloped ENS
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10
Q

The gut microbiome develops…

A

at approximately the same time postnatal development finishes.

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11
Q

factors in normal microbiome development

A
  • microbe exposure (birth canal, skin)
  • infant diet (breast milk)
  • immune sytem development
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12
Q

disturbances to microbiome development

A

cause deviations from microbial homeostasis
* antibiotics (at birth or during infancy)
* microbe exposure (C-section, infection)
* diet (breast/formula; weaning pattern)

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13
Q

deviance from immune homeostasis

A

cause immune-mediated diseases in later childhood
* asthma
* atopic disease
* T1D
* Crohn’s & Colitis

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14
Q

gut microbiome

A

the stable resident microbial community of a defined habitat (gut) in an individual person.

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15
Q

Bacterial numbers in stomach & small/large intestine

A
  • Stomach - continually exposed to microbes, but very few actually grow there.
  • Distal Small intestine (mainly ileum) - site of stable occupation by microbes. Lower numbers than colon.
  • Large intestine (colon) - has distinct conditions for microbial growth and far higher microbe cell density than ileum.
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16
Q

Over 98% of the total microbial cells in our gut are Bacteria .

A

true!

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17
Q

Bacteroidetes (10-90% of all cells)

A
  • Tens to hundred of Bacteroidetes species
  • Vast majority show fermentative metabolism
  • Diverse growth substrates commonly polysaccharides
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18
Q

Firmicutes (10-90% of all cells)

A
  • Hundreds of Firmicutes species.
  • Vast majority show fermentative metabolism.
  • Diverse growth substrates commonly polysaccharides
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19
Q

Proteobacteria (1–5% of all cells)

A
  • Tens of Proteobacteria species.
  • Respiratory and fermentative metabolism
  • Growth substrates rarely polysaccharides, commonly small molecules (sugars, amino acids and fatty acids).
20
Q

Methanobrevibacter (1-2%)

A
  • One or two species.
  • One type of metabolism (methanogenesis).
  • Growth on one-carbon compounds and hydrogen.
21
Q

The presence of microbes changes our food requirements

A
  • Quantity - Less food is eaten by animals that are colonised.
  • Quality - The diet fed to germ-free animals requires vitamin supplementation and a simple carbohydrate profile.
22
Q

Small intestine

A

Tank for further hydrolysis.
* Cells of accessory organs secrete enzymes and bile.
* Intestinal epithelial cells absorb nutrients.

23
Q

Stomach

A
  • An acid hydrolysis tank.
  • Gastric cells secrete acid and enzymes
24
Q

Material passing to the colon includes…

A

Indigestible - chemically inaccessible to human enzymes (e.g. fibre)
Inaccessible – particle structure prevents enzyme access (e.g. intact corn kernel)
Excess – exceeded digestion/absorption capacity of small intestine.

25
Q

Plant cell walls…

A

are digestion resistant (e.g. cellulose, xylan).
* Starch must be released to be degraded by amylases.
* Other storage polysaccharides of plants are typically also digestion-resistant (e.g. inulin, arabinogalactans).

26
Q

Ruminants Vs. Humans

A

Ruminants: up to 70% of calories via rumen microbes
Humans: 10 – 15% of calories via colon microbes

27
Q

Plant specialists

A

have complex digestive tract with a specialised fermentation chamber

28
Q

meat-specialists

A

simple digestive tract

29
Q

Short Chain Fatty Acids

A

SCFA are fermentation metabolites that are valuable energy sources for animals

30
Q

Most common metabolism is Fermentation Simple Carbs to…

A
  • Acetate, CO2, H2
  • Propionate, CO2, H2
  • Butyrate, CO2, H2
  • mixed SCFA, CO2, H2
  • human energy sources : intestinal gases
31
Q

Sulphate reduction

A

A specialised respiratory metabolism
* SCFA -> CO2 + H2S
* Toxic molecules

32
Q

Other bioactive microbial metabolites include…

A
  • Bile acid derivatives DCA and LCA
  • Neurotransmitter production (serotonin, GABA)
  • Vitamin production
  • Amino acid production
  • human essential nutrients
33
Q

The net effect of microbial metabolites on our health is a product of:

A
  • Food items/diet
  • Microbial activity
  • Types of microbes
  • Adaptive responses
34
Q

“Nutrient control”

A

determines population size and activity in the gut (encourages functions we need):
* Body directs bacteria to use fibre - rapidly absorbs other nutrients
* Body selects for fermentative metabolism – excludes oxygen, removes iron
* Body supports growth on fibre - adds back nitrogen ‘fertiliser (uric acid, urea)
* Body limits total bacterial biomass - poops often
* Bacteria trained to ‘do the right thing’: stay in gut, grow on fibre, release SCFA

35
Q

Immune functions contain bacterial activity within the gut (Punish activities we don’t need)

A
  • Intestinal mucosal surface limits bacterial contact with epithelium
  • Immune defences kill bacteria at epithelium.
  • The lamina propria (adjoining intestinal tissue) is kept ‘sterile’
  • Bacteria near the wrong place, or in the wrong place, are not tolerated
36
Q

Microbe interaction with immune system

A
  • Immune system has functions in preventing and resolving infections at all body sites.
  • Immune system is also potentially dangerous – today chronic diseases involving immune-metabolic dysfunction are the major health burden
37
Q

Key features of Pathogens

A
  • Not normally present
  • Presence is associated with disease consistently
  • Experimental infection is sufficient to cause disease.
  • “Specialist pathogens”
  • EXCLUDE from body
38
Q

Key features of Commensals

A
  • Normally present
  • Absence leads to abnormal physiology (in experimental Germ-free animals).
  • May indirectly contribute to disease
  • “Potential pathogens”
  • “Opportunistic pathogens”
  • ENCOURAGE in some parts and EXCLUDE from others
39
Q

Defence against pathogens involves…

A
  1. Colonisation resistance
  2. Barrier functions
  3. Immune functions
40
Q

Pathogens can colonise…

A
  • on external body surface (skin, teeth etc.)
  • internal cavity (gut lumen)
  • internal mucosal surface (epithelium of lung etc.)
41
Q

direct effect of pathogen

A

produce toxin or tissue-destructive enzyme
OR
Obstruction

42
Q

MAMPs

A

Microbe-associated Molecular Patterns

43
Q

DAMPs

A

Damage-associated Molecular Patterns

44
Q

Immune tone

A
  • Differences in immune tone are major factors in different infectious disease severity.
  • Change in immune tone is a major factor in development of chronic diseases.
  • The gut microbiome is a factor in modulation of immune tone.
45
Q

Dysbiosis

A

a term for diseases of a poorly functioning symbiosis

46
Q

Is our risk for infection tightly inter-related with our microbiome?

A

YES - Opportunistic pathogens typically co-occur with normal microbes in our gut and specialist pathogens can invade our gut.

47
Q

The biggest disease burdens today are characterised as…

A

chronic immuno-metabolic diseases.
* Nearly all of them are nutrition-related and microbiome-related