The Microbiota of the GIT Flashcards
Where is the start of the GIT?
Mouth
Where does the GIT run to?
Rectum/anal canal
What is the transit time in the mouth?
1 min
What is the transit time in the oesophagus?
4-8sec
What is the transit time in the stomach?
2-4hr
What is the transit time in the small intestine?
3-5hr
What is the transit time in the colon?
10hr-several days
What does transit time affect?
- Bacterial populations due to different bacterial growth rates
- Intestinal cell exposure to toxins consumed with food or produced by bacteria
What happens to the size of bacterial populations as you go down the GIT?
Increase
Why doe bacteria populations increase in size as you go down the GIT?
- Increasingly anaerobic conditions
- Increasing bacterial density
- Increasing dominance of obligate anaerobes
Bacterial population size in stomach?
10^3-10^4/ml
Bacterial population size in small intestine?
10^8/ml
Bacterial population size in colon?
10^10-10^11/ml
Anaerobic
Living in the absence of air
Aerobic
Living in the presence of air
Facultative anaerobic bacteria
- Can grow in the presence of air
- Can grow in the absence of air
Obligate anaerobe
- Cannot grow in the presence of oxygen
- Many rapidly killed in the presence of oxygen
What happens to the dominant bacteria along the GIT?
Change
Why do the dominant bacteria change along the GIT?
Due to different:
- Oxygen concentrations
- pH
- Transit times
What happens to the pH along the GIT?
- Mouth pH 6.5>7.5
- Stomach pH 1.4>4
- Duodenum pH 7>8.5
- Distal ileum pH 4>7
- Colon pH 5.5>6.5
What do the large numbers of bacteria mean?
- There are more microbial than human cells in the body
- These microbes are important for out health and what we eat can impact their activities
- The average human adult will poop their own body weight in bacteria every 1-2 years
What are the taxonomy and bacterial classifications in order from generic to specific?
- Life
- Domain
- Kingdom
- Phylum
- Class
- Order
- Family
- Genus
- Species
What is the bacterial diversity od the large intestine?
- 4 major phyla
- > 200 genera
- > 1250 species
At what level do meaningful comparisons have to be made?
Genus level
How do bacteria act together?
In a population/consortium
What is important to maintain health?
A diverse microbiota
What do different bacteria do?
Perform different functions
What are the vast majority of the resident bacteria in the GIT beneficial for?
Health
What does the GIT microbiota do?
- Defence against pathogens
- Modification of host secretions
- Metabolism of dietary components
- production of essential metabolites to maintain health
- Development of immune system
- Host signalling
What does healthy gut microbiota lead to?
Healthy person
How does GIT microbiota defend against pathogens?
- Competition
- Barrier function
- pH inhibition
Why does junk food not feed our gut microbes?
Energy absorbed in stomach/small intestine
Where doe GIT microbes grow?
On the fibre we eat in foods like fruit, vegetables, pulses and whole grains and convert it into thousands of different products
What can GIT microbe also use for growth?
Endogenous (host-derived) substrates
What similarities are there between the small intestine and large intestine?
- Gut lumen
- Epithelial surface
- Goblet cells
- Crypts
- Muscular layer
What are the benefits of including dietary fibre in our diet?
- Improves faecal bulking, eases passage, results in shorter transit time
- Contains important phytochemicals, anti-oxidants and vitamins
- Bacterial fermentation
What does bacterial fermentation result in?
- Releases additional phytochemicals
- Maintains slightly acidic pH
- Increased commensal bacterial population and pH improves resistance to pathogens
- essential supply of short chain fatty acids
What happens in the small intestine?
- Digestion of dietary carbohydrate, starches, sugars, fat, protein
- Absorption of monosaccharides, fat, amino acids, soluble phytochemicals
What happens in the large intestine?
- Microbial fermentation of non-digestiable carbohydrates
- Absorption of SCFA, BCFA, gases, phytochemicals, other metabolites and minerals
What is disposed of in faeces?
Undigested carbohydrate, lignin, unabsorbed nutrients
What are the 3 main short chain fatty acids?
- Butyrate
- Propionate
- Acetate
What does the ratio of SCFA depend on?
- Substrate availability
- Bacterial composition
What is the function of butyrate?
Epithelial cell growth and regeneration
What is the function of propionate?
- Gluconeogenesis in the liver
- Satiety signalling
What is the function of acetate?
- Transport in blood to peripheral tissues
- Lipogenesis
Describe the metabolism of gut microbia in the proximal colon.
- Carbohydrate rich
- pH mildly acidic
- Turnover rapid
Describe the metabolism of gut microbial in the distal colon.
- Little fermentable carbohydrate
- pH neutral
- Turnover slow
What are the major products and gases produced by CHO metabolism?
- Acetate, propionate, butyrate
- CO2, H2, CH4
What are the major products and gases produced by protein metabolism?
- Branched SCFA
- NH3, H2S
What is the link between diet, microbes and health?
- Specific combinations of gut microbes and food are beneficial for our health and others are detrimental
- Many important gut microbial activities are driven by what we eat
What does a diverse balanced diet lead to?
- A diverse balanced microbiota
- Diverse balanced products
What are the 2 mechanisms that helps in defence against pathogens?
- Barrier effect
- Active competitive exclusion
What is the barrier effect?
-The large numbers of the indigenous microbiota prevent colonisation by ingested pathogens and inhibit overgrowth of potentially pathogenic bacteria normally resident at low levels
What is the active competitive exclusion conferred by?
Both microbe-microbe and microbe-host interactions
How do the mucus layers differ in bacterial content?
- Outer layer: contains bacteria
- Inner layer: normally few bacteria
How does the difference in bacterial colonisation between the mucus layers keep the gut health?
The mucus layer forms a barrier between the luminal bacterial population and the epithelial cells
Describe the defences against pathogens at each layer.
- Commensal bacteria close to the epithelium black and prevent adhesion/colonisation by pathogens
- Outer mucus layer barrier effect
- Inner mucus layer prevents bacterial penetration
- The few bacterial cells that penetrate through the epithelium are dealt with efficiently by the immune system
What does a normal immune response lead to?
Homeostasis
What does a dysregulated immune response lead to?
Inflammation
Describe pH inhibition.
Generally pathogens grow optimally at pHs over 6
Why is there less disease in the proximal colon?
- High substrate concentrations
- High fermentation rates
- High SCFA production and absorption
- Low pH: pathogen exclusion
- Quicker transit: high epithelial cell turnover
Why is there more disease at the distal colon?
- Low substrate concentrations
- Low fermentation rates
- Low SCFA production and absorption
- Higher pH: less pathogen exclusion and more protein fermentation
- Slower transit time: higher exposure to harmful compounds
What is the largest lymphoid organ in the body?
Gut
What is the is the commensal bacteria population of the gut?
10^10-10^11 bacteria/g gut contents
What must the gut be able to do from an immune response point of view?
- Respond appropriately to foreign/pathogenic agents
- Actively down regulate immune responses to self proteins, dietary antigens and the commensal microbiota
- Recognise and respond to pathogen invasion
Some gut microbiota species are pro-inflammatory while other are ….
Anti-inflammatory
What doe pattern recognition receptors do?
Detect and bind different molecules associated with pathogens, microbe or cell components
What do Toll like receptors specifically recognise?
Bacterial components
What does activation of PRRs trigger?
- Molecular signally cascades
- Co-ordinated production of pro-inflammatory cytokines, chemokines and co-stimulatory molecules
What is inflammation an interplay between?
Pro- and anti-inflammatory cytokines
Name a pro-inflammatory cytokine?
IL-6
Name an anti-inflammatory cytokine?
IL-10
What are TLRs?
- Specific proteins involved in the innate immune system
- Membrane spanning non-catalytic receptors
Where are TLRs expressed?
Epithelial cells like macrophages and dendritic cells
What do TLRs recognise?
Microbial molecules that are structurally conserved
When do autoimmune diseases occur?
When the immune system can no longer distinguish between harmful detrimental pathogens and the commensal bacteria
What can dysbiosis of the gut microbiota lead to?
Disruption of homeostasis leading to gut inflammation
SCFA are important signally molecules that impact on…
- Gut health
- Metabolic health
- Brain health
- Overall health
What detects SCFA?
Receptors on gut epithelial
Name three signals activated by SCFA?
- FFAR2
- FFAR3
- GPR109A
What activates FFAR2 and what does it result in?
- Acetate, propionate
- GLP-1 secretion (inhibits fat accumulation)
What activates FFAR3 and what does it result in?
- Propionate, butyrate
- PYY secretion (improves insulin resistance and satiety signalling to the brain)
What activates GPR109A and what does it result in?
- Butyrate
- Suppresses colonic inflammation and carcinogenesis (anti-inflammatory cytokine )
How does microbial composition vary through life?
- Changes
- Baby considerably different to elderly
- Baby dependent on type of feeding
What is the greatest influence on our guts microbiota population?
Diet
What is the most densely populated body site colonised predominantly by anaerobic bacteria?
Large intestine
What do the bacteria in the large intestine ferment and what is the result?
- Dietary fibre
- the metabolite produced like SCFA are important for health and circulate round the body having effects outside the gut
