The Gut Microbiota in Health and Disease Flashcards
What is the transit time in the mouth?
1 minute
What is the transit time in the oesophagus?
4-8 seconds
What is the transit time in the stomach?
2-4 hours
What is the transit time in the small intestine?
3-5 hours
What is the transit time in the colon?
10 hours to 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
How does the amount of bacteria change as you go down the GI tract from the stomach to the colon?
Increases
What does anaerobic mean?
Living in the absence of oxygen
What does aerobic mean?
Living in the presence of oxygen
What are different classes of anaerobic bacteria?
Facultative anaerobic bacteria
Obligate anaerobic bacteria
What are facultative anaerobic bacteria?
Can grow in the presence of oxygen and in the absence of oxygen (some grow poorly when oxygen is present)
What are obligate anaerobes?
Cannot grow in the presence of oxygen (many rapidly killed in the presence of oxygen)
What are examples of bacteria found in the stomach?
Lactobacillus
Candia
Streptococcus
Helicobacter pylori
What are examples of bacteria found in the colon?
Bacteroides
Clostridium
Bifidpbacterium
Enterobacteriaceae
What class of anaerobes are found in the stomach?
Faciltative anaerobes
What class of anaerobes is found in the colon?
Obligate anaerobes
Why do different kinds of bacteria dominate different areas of the GI tract?
Different oxygen concentrations
Different pH
Different transit times
How does the number of microbial cells compare to human cells?
There are more microbial cells
How much bacteria is there in the human gut?
100 trillion
What are the different parts of taxonomy?
Life
Domain
Kingdom
Phylum
Class
Order
Family
Genus
Species
Why must meaningful comparison between bacteria be done at the genus level?
Bacterial comparison at the phylum level is a higher level than grouping all mammals together
What impact does diet have on bacteria?
Impacts diversity
What does OTU stand for?
Operational taxonomic unit
What does a higher number of OTUs mean?
Higher diversity
What are some functions of gut microbiota?
Modifications of host secretions (mucin, bile, gut receptors etc)
Defence against pathogens
Metabolism of dietary components
Production of essential metabolites to maintain health
Development of the immune system
Host signalling
How does the gut microbiota provide defence against pathogens?
Competition
Barrier function
pH inhibition
What host secretions do the gut microbiota modify?
Mucin
Bile
Gut receptors
Why is junk food bad although it contains lots of energy (calories)?
Does not feed out gut microbes, that grow on fibres
Energy absorbed in stomach/small intestine
>70% of energy uptake?
What kinds of food is fibre found in?
fruit, vegetables, pulses and whole grains
Where are the products created by bacteria that are derived from fibres absorbed?
Energy absorbed in large intestine
5- 10% of energy uptake
As well as fibre, what else can GIT microbes use for growth?
endogenous (host-derived) substrates for growth
What are benefits of including dietary fibre in our diet?
mproves faecal bulking, eases passage, results in shorter transit time
Contains important phytochemicals, anti-oxidants and vitamins
How does bacterial fermentation impact pH?
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 are the benefits of bacterial fermentation?
Increased commensal bacterial population and pH improves resistance to pathogens
Essential supply of short chain fatty
acids
What are the 3 main fatty acids provided by bacterial fermentation?
(SCFAs) acetate (C2), propionate (C3), and butyrate (C4)
What are the functions of butyrate?
Epithelial cell growth
and regeneration
What are the functions of propionate?
gluconeogenesis
in the liver
Satiety signalling
What are the functions of acetate?
Transported in blood
To peripheral tissues
lipogenesis
what does a diverse balanced diet result in?
A diverse balanced microbiota,
diverse balanced products
How much carbohydrates are metabolised by bacteria per day?
40g/day
what are the major products of carbohydrate metabolism?
SCFA – acetate, propionate, butyrate
Gases – CO2, H2, CH4
how much protein is metabolised per day?
(12 – 18g/day
what are the major products of protein metabolism?
Branched SCFA -iso-butyrate, isovalerate
Gases – NH3, H2S
Phenols, indoles, amines
where is the site of most bacterial fermentation?
the right side (proximal) colon
describe the right side (proximal) colon
carbohydrate rich
PH mildly acidic
rapid turnover
describe the left side (distal) colon
little fermentable carbohydrate
PH neutral
Turnover slow
where is the site of most intestinal disease?
left side (distal) colon
what does the large intestine receive from ileum?
dietary polysaccharides
prebiotics
peptides
how does the bile concentration differ from the proximal colon to the distal colon?
becomes more concentrated
what is the ratio of butyrate to propionate to acetate?
1:1:3
what does the low PH in the proximal colon allow?
pathogen inhibition
increased calcium absorption
what is the PH of the transverse colon?
6
what is the PH of the distal colon?
6.5
what does having fibre in your diet allow?
Increased faecal bulking
Increased gut transit rate
at what PH do pathogens optimally grow at?
PH over 6
what are the concentrations of substrates, fermentation and SCFA production and absorption in proximal colon?
High substrate concentrations High fermentation rates
High SCFA production and absorption
what are the concentrations of substrates, fermentation and SCFA production and absorption in distal colon?
Low substrate concentrations Low fermentation rates
Low SCFA production Low SCFA absorption
what is the transit time and epithelial cell turnover like for proximal colon?
quicker transit time
high epithelial turnover
what is the transit time and epithelial cell turnover like for distal colon?
slower transit
Higher exposure to harmful compounds
what is the barrier effect with colonisation resistance?
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 with colonisation resistance?
conferred by both microbe-microbe and microbe-host interactions
what are the systemic effects of bacterial fermentation?
SCFA production and absorption
Butyrate
Propionate
Acetate
Transported in blood to liver, peripheral tissues, brain,
Signalling molecules (immune system, brain)
why are short chain fatty acids important?
important signalling molecules
impact on gut health, metabolic health, brain health, overall health
what do receptors on gut epithelial cells do?
detect SCFA and secrete gut hormones
what activates GPR43/FFAR2?
acetate, propionate > butyrate
what does GPR43/FFAR2 activation result in?
GLP-1 secretion (inhibits fat accumulation)
what activates GPR41/FFAR3?
propionate and butyrate
what does GPR41/FFAR3 activation result in?
results in PYY secretion (improves insulin resistance and satiety signalling to brain)
what activates GPR109A?
butyrate
what does GPR109A activation result in?
suppresses colonic inflammation and carcinogenesis
(anti-inflammatory cytokines eg. IL-10)
what effect does the outer mucus layer barrier have on immune system?
Commensal bacteria close to epithelium block and prevent adhesion/colonisation by pathogens
what is the role of the inner mucus layer?
prevents bacterial penetration
The few bacterial cells that penetrate through the epithelium are dealt with efficiently by the immune system
Surface is in constant interaction with the external environment, what must it be able to do?
Must be able to
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
what is essential to maintain health of the host?
The maintenance of homeostasis between the gut microbiota and the host
immune system is essential to maintain health of the host.
when do autoimmune diseases occur?
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 composition lead to?
Dysbiosis of the gut microbiota composition can disrupt the homeostasis and can lead to gut inflammation
what are two categories of gut microbiota?
pro-inflammatory, while others are anti-inflammatory
Prenatal immature immune system
A baby’s immune system is not fully developed when they are born. It gets stronger as the baby gets older. The immune system works throughout our lives fighting germs that can cause disease. A mother’s antibodies are shared with their baby through the placenta during the third trimester (last 3 months) of pregnancy
Postnatal immune system – ‘learns’ from bacterial
Postnatal microbiota
Breastmilk itself contains viable bacteria originating from the maternal gut and infant oral cavity that influences the composition of the enteric microbiome. Exclusive breast-feeding in the first 4 months of life was found to prevent atopic dermatitis (AD) in infants at high risk of atopy.
what are diseases of the CNS that are linked to dysbiosis of the gut microbiota?
Autistic Spectrum Disorders
Major Depressive Disorders
Multiple sclerosis
what are diseases of the GI tract that are linked to dysbiosis of the gut microbiota?
IBD (CD, UC)
IBS
NAFLD
Cirrhosis
what are diseases affecting metabolism that are linked to dysbiosis of the gut microbiota?
Insulin resistance (T2D)
Metabolic syndrome
Obesity
CVD
what are diseases affecting immunity that are linked to dysbiosis of the gut microbiota?
Allergies
Auto-immune diseases
Cancer immunotherapy
what two chronic inflammatory diseases does IBD encompass
Crohn’s Disease (CD)
Ulcerative Colitis (UC)
what do many studies show about the relationship between IBD, obesity and diversity of microbiota?
the microbiota is less diverse
What features of IBD may cause a less diverse microbiota?
Antibiotic use
Reduces bacterial diversity and increases Enterobacteriaceae
Inflammation
Diarrhoea
Decreased transit time alters microbial composition
Host diet
May be a desire to eat less fibre, changes microbiota composition
Host genotype
what are consequences of exposure to antibiotics
Most antibiotics are broad-spectrum antibiotics active against target pathogen but also ‘kill’ commensal bacteria change bacterial composition
Reduced bacterial diversity and increases in Proteobacteria (Enterobacteriaceae) can occur as a result of broad-spectrum antibiotic use
BUT antibiotic necessary to treat disease:
Use: as little as possible BUT as often as necessary
how should antibiotics be used?
as little as possible BUT as often as necessary
what is another issue caused by antibiotic treatment?
Antibiotic treatment also causes the spread of antibiotic resistance
what effect does selective pressure have on diversity?
decreases diversity
Different antibiotics have different impacts on the intestinal microbiota such as…
Vancomycin > Clindamycin > Ciprofloxacin
what effect does antibiotics have on Firmicutes, Bacteroidetes and Proteobacteria
Generally Firmicutes and Bacteroidetes decline and Proteobacteria increase
what are some consequences of exposure to antibiotics?
Decreased microbial diversity affected abundance of 1/3 bacterial taxa
indiscriminate effect
Within 4 weeks of treatment ceasing, community composition almost back to pretreatment state
Opportunity for pathogen colonisation
Results in pathogen dominated community
Clostridium difficile expands to occupy empty niches
following antibiotic therapy
Overgrowth of C. difficile results in toxin production,
abdominal pain, fever (CDAD)
what issues arise with C.difficile infections following antibiotic treatment?
Overgrowth of C. difficile results in toxin production,
abdominal pain, fever (CDAD)
C. difficile spores are resistant to antibiotics
Some C. difficile strains are antibiotic resistant
Results in recurring C. difficile infections
what can reduce the incidence of CDAD
Use of probiotics in intensive care units can reduce
incidence of CDAD
Faecal Microbial Transplant (FMT) therapy
proven effective
Faecal Microbial Transplant (FMT) therapy how does it work?
Faecal sample from screened healthy
donor transplanted into recipient
Donor microbiota repopulates large intestine, displaces C. difficile, prevents reinfection
Success rate depends on clinic experience, application method, pretreatment (stopping antibiotics beforehand), no subsequent antibiotic treatment etc
what are factors that affect gut microbiota?
disease
faecal transplant
prebiotics
antibiotics
probiotics
environment
diet
lifestage
what is a probiotic?
Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host
Probiotics are ADDED LIVE BACTERIA
what is a prebiotic?
A prebiotic is a substrate that is selectively utilized by host microorganisms conferring a health benefit
Prebiotics are FOOD for resident bacteria
what are widespread mechanisms of probiotics
Competition
Competitive exclusion
Barrier function
Reduce inflammation
Some mechanisms are widespread carried out by many bacteria (genus or species relatively unimportant)
what are frequent mechanisms for probiotics?
Bioconversions (diet)
Direct antagonism (pathogens)
Immune stimulation
what are rare mechanisms for probiotics?
Production of vitamins
what are metabolic health benefits of prebiotics?
Metabolic effects
EFSA positive opinion: Inulin/FOS can lower glycaemic index” (Jan 2014)
“consumption of foods containing non-digestible carbohydrates instead of sugars
induces a lower blood glucose rise after meals compared to those containing sugars”
Health benefit – ↑ insulin sensitivity, ↓ lipid accumulation,
↑ barrier function, ↓ inflammation
what are satiety metabolic health benefits of prebiotics?
Health benefit – ↑ increased PYY, GLP-1 secretion
↑ increased satiety, ↓ food intake
what are Immunomodulatory effects of prebiotics
Health benefit – ↑ immune boosting, ↓ inflammation (IBD, IBS)
↓ allergic reactions
Bone health (FOS/Inulin) increase calcium absorption and bone health
pH effect
Infant health (GOS/FOS) supplementation of infant formula increases
bifidobacteria numbers (pathogen exclusion, lactate formation)
