human microbiome Flashcards
The microbes we are exposed to may…
- 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)
Do we have microbes in utero?
No! However after birth the residence of TRILLIONS of microbes is normal
Microbial metagenome is much larger than
human genome?
True
The presence of microbes in tissues is…
NOT normal.
Tight gut barrier
mucin layer over tightly joined epithelial cells
* excludes microbes from the underlying tissues of our body
* mucin layer - lubricating barrier
Parasitism
Partner 1 benefits - increased growth output for parasite/pathogen
Partner 2 harmed - reduced growth output for ‘host’
Host better without parasite
Commensalism
Partner 1 benefits - increased growth output for commensal
Partner 2 neutral - no growth change for host
Host same with/without commensal
Mutualism
Partner 1 benefits - increased growth output for mutualist
Partner 2 benefits - improved growth for host
Host needs microbe for optimal fitness
In the absence of Microbes…
- 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
The gut microbiome develops…
at approximately the same time postnatal development finishes.
factors in normal microbiome development
- microbe exposure (birth canal, skin)
- infant diet (breast milk)
- immune sytem development
disturbances to microbiome development
cause deviations from microbial homeostasis
* antibiotics (at birth or during infancy)
* microbe exposure (C-section, infection)
* diet (breast/formula; weaning pattern)
deviance from immune homeostasis
cause immune-mediated diseases in later childhood
* asthma
* atopic disease
* T1D
* Crohn’s & Colitis
gut microbiome
the stable resident microbial community of a defined habitat (gut) in an individual person.
Bacterial numbers in stomach & small/large intestine
- 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.
Over 98% of the total microbial cells in our gut are Bacteria .
true!
Bacteroidetes (10-90% of all cells)
- Tens to hundred of Bacteroidetes species
- Vast majority show fermentative metabolism
- Diverse growth substrates commonly polysaccharides
Firmicutes (10-90% of all cells)
- Hundreds of Firmicutes species.
- Vast majority show fermentative metabolism.
- Diverse growth substrates commonly polysaccharides
Proteobacteria (1–5% of all cells)
- Tens of Proteobacteria species.
- Respiratory and fermentative metabolism
- Growth substrates rarely polysaccharides, commonly small molecules (sugars, amino acids and fatty acids).
Methanobrevibacter (1-2%)
- One or two species.
- One type of metabolism (methanogenesis).
- Growth on one-carbon compounds and hydrogen.
The presence of microbes changes our food requirements
- 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.
Small intestine
Tank for further hydrolysis.
* Cells of accessory organs secrete enzymes and bile.
* Intestinal epithelial cells absorb nutrients.
Stomach
- An acid hydrolysis tank.
- Gastric cells secrete acid and enzymes
Material passing to the colon includes…
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.
Plant cell walls…
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).
Ruminants Vs. Humans
Ruminants: up to 70% of calories via rumen microbes
Humans: 10 – 15% of calories via colon microbes
Plant specialists
have complex digestive tract with a specialised fermentation chamber
meat-specialists
simple digestive tract
Short Chain Fatty Acids
SCFA are fermentation metabolites that are valuable energy sources for animals
Most common metabolism is Fermentation Simple Carbs to…
- Acetate, CO2, H2
- Propionate, CO2, H2
- Butyrate, CO2, H2
- mixed SCFA, CO2, H2
- human energy sources : intestinal gases
Sulphate reduction
A specialised respiratory metabolism
* SCFA -> CO2 + H2S
* Toxic molecules
Other bioactive microbial metabolites include…
- Bile acid derivatives DCA and LCA
- Neurotransmitter production (serotonin, GABA)
- Vitamin production
- Amino acid production
- human essential nutrients
The net effect of microbial metabolites on our health is a product of:
- Food items/diet
- Microbial activity
- Types of microbes
- Adaptive responses
“Nutrient control”
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
Immune functions contain bacterial activity within the gut (Punish activities we don’t need)
- 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
Microbe interaction with immune system
- 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
Key features of Pathogens
- Not normally present
- Presence is associated with disease consistently
- Experimental infection is sufficient to cause disease.
- “Specialist pathogens”
- EXCLUDE from body
Key features of Commensals
- 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
Defence against pathogens involves…
- Colonisation resistance
- Barrier functions
- Immune functions
Pathogens can colonise…
- on external body surface (skin, teeth etc.)
- internal cavity (gut lumen)
- internal mucosal surface (epithelium of lung etc.)
direct effect of pathogen
produce toxin or tissue-destructive enzyme
OR
Obstruction
MAMPs
Microbe-associated Molecular Patterns
DAMPs
Damage-associated Molecular Patterns
Immune tone
- 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.
Dysbiosis
a term for diseases of a poorly functioning symbiosis
Is our risk for infection tightly inter-related with our microbiome?
YES - Opportunistic pathogens typically co-occur with normal microbes in our gut and specialist pathogens can invade our gut.
The biggest disease burdens today are characterised as…
chronic immuno-metabolic diseases.
* Nearly all of them are nutrition-related and microbiome-related
