Microbiota of the GIT Flashcards
Describe transit time in relation to section of GIT
Transit time gets longer from mouth to large intestine
In large intestine for 10hrs to several days
Stomach 2-4hrs and small intestine 3-5hrs
How does transit time affect the microbiota?
Bacterial population effected due to different bacterial growth rates
Also intestinal cell exposure to toxins
Describe the bacterial populations along the GIT
Increasing anaerobic conditions
Increasing bacteria density
Increasing dominance of obligate anaerobes
What is the total number of bacteria in the human gut?
Up to 100 trillion
Everyone’s microbia is different - unique
Why is there a dominant bacteria change along the GIT?
Different oxygen conc., different pH and different transit times
What are the pH changes of the GIT?
Mouth - 6.5-7.5
Stomach - 1.5-4
Duodenum - 7-8.5
Ileum - 4-7
Large Colon - 5.5-6.5
Why does microbial composition change throughout life?
Anatomy is the same but food is different
Our food is microbiota’s food
What is the role of the GIT microbiota?
Metabolism of dietary components
Production of metabolites
Modification to host secretions
Defence against pathogens
Development of immune system
Host signalling
What does healthy gut microbiota equal?
Healthy person
Is junk food good for microbes?
Junk food provides a lot of calories but does not feed gut microbes as does not reach large colon
Most absorbed in small intestine/stomach - 70% energy uptake
What food does GIT microbes grow on?
Fibre - fruit, veg, pulses and whole grains
Converts to different products
Energy absorbed in large intestine
What are the benefits of including dietary fibre in our diet?
Improves faecal bulking, eases passage and results in shorter transit time
Contains phytochemicals, antioxidants and vitamins
Bacterial fermentation
What does bacterial fermentation do?
Releases additional phytochemicals
Maintains slightly acidic pH
Increased commensal bacterial population
Essential supply of short chain fatty acids
What is the right side of the colon responsible for?
Site of most bacterial fermentation
Carbohydrate metabolism
Gives SCFA and gases
What does a diverse balanced diet do microbes?
A diverse balanced microbiota and diverse balanced products
What we eat affects amount and type of microbial metabolites produced
What does SCFA give?
Acetate, propionate and butyrate
What is the left side of the colon responsible for?
Site of most intestinal disease
Protein metabolism
Major products
Branched SCFA, gases, phenols, indoles and amines
What are the 3 main short chain fatty acids?
Butyrate, propionate and acetate
What is the function of butryrate?
Epithelial cell growth and regeneration
What is the function of propionate?
Gluconeogenesis in the liver
Satiety signalling
What is the function of acetate?
Transported in blood and to peripheral tissues
Lipogenesis
What does pH lowering help?
Pathogen inhibition
Increased Ca absorption
What is the optimum pH for growth of pathogens?
Over 6
Describe pH and proximal colon
Low pH so pathogen exclusion - Less disease
Quicker transit
High epithelium turnover
High fermentation rates
High SCFA production
Describe pH and distal colon
Higher pH - less pathogen exclusion and more protein fermentation - more disease
Low substrate concentrations
Slower transit so higher exposure to harmful compounds
What are the 2 defences which help colonisation resistance?
Barrier effect
Active competitive exclusion
What is barrier effect?
Large numbers of indigenous microbiota prevent colonisation by ingested pathogen and inhibit overgrowth of pathogenic bacteria
This bacteria could be normally at low levels
What is active competitive exclusion?
Both microbe to microbe and microbe to host interactions
What happens to the products of the bacteria?
transported in blood to liver, peripheral tissues, brain and signalling molecules
Why are short chain fatty acids important?
Important signalling molecules
How are SCFA detected?
By receptors which secrete gut hormones
What are the GPR43/FFAR2 receptors activated by?
Acetate, propionate more than butyrate
What are GPR41/FFAR3 receptors activated by?
Propionate and butyrate
What are GPR109A receptors activated by and what do they do?
Butyrate
Suppress colonic inflammation and carcinogenesis
Describe gut microbiota in the development of he immune system
Commensal bacteria close to epithelium block adhesion by pathogens
Inner mucus layer prevents bacterial penetration
Immune system deals with few bacteria cells leaving epithelium
Are microbiota species pro or anti-inflammatory?
Can be either
What does bacterial composition and metabolite conc. also effect?
Gut-brain axis
What are some non-gut conditions associated with changing of gut microbiota?
CNS - Multiple sclerosis
GI - IBD, IBS
Metabolism - Insulin resistance, obesity
Immunity - allergies, autoimmune disease
What are the 2 diseases in inflammatory bowel disease?
Chron’s Disease and Ulcerative Colitis
What can dysregulation of immune response lead to?
Chronic gut inflammation
Autoimmune disease
What does inflammation in IBD likely result from?
Dysregulated host immune response to gut microbiota
What do CD patients have a lower number of?
F. prausnitizil - anti-inflammatory bacteria
Instead an increase in pro-inflammatory
What is the effect of antibiotic use and gut microbiota?
Reduces bacterial diversity and increases enterobacteria
Explain the vicious cycle in IBD
Decrease in mucus barrier then increase in O2 pressure
Then alters microbial composition
Which increases inflammation then continues again
What are some causes for change in gut microbial composition?
Antibiotic use
Inflammation
Diarrhoea - decreased transit time
Host diet - less fibre
Host genotype
What decreases diversity of bacteria when antibiotics used?
Selective pressure
There is increase in resistant community
Gradual recovery but never bac to normal
What antibiotics have more effect on intestinal microbiota?
Vancomycin > clindamycin > ciprofloxacin
What are the consequences of exposure to antibiotics?
Decreased microbial diversity
Opportunity fir pathogen colonisation so results in pathogen dominant community
Can end up with recurrent C. difficile infections
What can reduce incidence of CDAD?
Probiotics
Explain a FMT
Faecal sample from screened healthy donor transplants into patient
This displaces C. difficile and prevents reinfection
What are the factors which affect gut microbiota?
Environment, diet, life stage, antibiotics, prebiotics, faecal transplant, disease
How does decreased dietary carbohydrate content effect faecal short chain fatty acid production?
Decreased production of SCFA
Significant decrease un numbers of E.rectale group
What are probiotics?
Live microorganisms that when administered in adequate amounts, confer health benefit on host
What are prebiotics?
Substrate that is selectively utilised by host microorganisms conferring health benefit
Prebiotics are food for resident bacteria
What are some widespread mechanisms carried out by prebiotics?
Competition
Competitive exclusion
Barrier function
Reduce inflammation
What are some frequent mechanisms carried out by prebiotics?
Bioconversions
Direct antagonism
Immune stimulation
How does prebiotics help satiety signalling?
Stimulate SCFA production by gut microbiota
Interact directly with immune cell receptors
What are the systemic effects of prebiotics?
Increased health benefit as metabolic effects, satiety an immunomodulatory effects
There is decreased inflammation
