Gut Immunity
Microbiota- large number of microorganisms which have colonised the GI tract
Contribute to our health and disease
Symbiotic and mutualistic relationship
4:3 in men
11:5- women
Firmicutes-most common
Found mostly in the colon
Killed off in the stomach
The foetus is exposed to microbes in the
uterus
Colonisation occurs after birth
Influenced by: mode of delivery, diet,
hygiene and antibiotic exposure
Bifidobacterium longum- present in breast
milk
Break down oligosaccharides-lactic acid
Reduces colonisation and pathogens
Age 3- adult like microbiota
Medication, diet, living environment- affect the
amounts and type of microbiota we have
Broad spectrum antibiotic use-can cause
dysbiosis
C diff affects the colon= arises after recent travel
or antibiotic use
Antibiotic resistance is a issue when treating C diff infections
Broad-spectrum kills off
commensals- fewer to fight
infections and remove noxious
stimuli- therefore, C-diff produes
toxins=injury, neutrophils and
RBCS leak into the epithelial cells.
How do commensal bacteria
contribute to health:
, Outcompete and limit pathogenic species
Degrade toxins to harmless components- for use
Produce vitamins eg vitamin K for clotting factor synthesis
Breakdown non-digestible carbohydrates into small molecules for absorption
Development of GI immune system and establishment of self- tolerance
Short chain fatty acid synthesis
Bacteria ferment non-digestible carbohydrates- short chain fatty acids
Eg acetate, propionate, butyrate
Acetate- cholesterol metabolism and lipogenesis
Propionate-regulates gluconeogenesis and satiety interacting with gut fatty acid
receptors
Butyrate- utilised by colon epithelial cells- suppression of inflammation
High levels of short chain fatty acids= lower risk of obesity and insulin resistance
=reduce risk of diabetes
Ob/Ob microbiota- heterozygous for leptin gene mutation
2 mutations in leptin gene = obesity
When given microbiota to other mice- significant weight gain
High abundance of firmicutes
Healthy gut microbiota Dysbiotic gut microbiota
Low gut permeability High gut permeability
Low endotoxemia High endotoxemia
Low pro-inflammatory cytokines High levels of pro-inflammatory cytokines
High levels of beneficial molecules- eg Low levels of beneficial molecules
short chain fatty acids
High insulin sensitivity Low insulin sensitivity
High levels of adipocity
High levels of obesity
High calorie intake
Environmental factors
Which cause dysbiosis: high fat and sugar diet, stress, antibiotics – predisposed to metabolic
diseases
Which cause symbiosis: healthy diet, lifestyle, prebiotics and probiotics
Prebiotics are special plant fibers that help healthy bacteria grow in your gut.
Probiotics are live bacteria and yeasts
Ileum-payers patches- clusters of T and B cells, follicular DCs and macrophages
Forms a germinal centre
Mucosal immune system must recognise and eliminate pathogens in the presence of non-
pathogenic microbes
What are the anatomical features of germ free mice:
Microbiota- large number of microorganisms which have colonised the GI tract
Contribute to our health and disease
Symbiotic and mutualistic relationship
4:3 in men
11:5- women
Firmicutes-most common
Found mostly in the colon
Killed off in the stomach
The foetus is exposed to microbes in the
uterus
Colonisation occurs after birth
Influenced by: mode of delivery, diet,
hygiene and antibiotic exposure
Bifidobacterium longum- present in breast
milk
Break down oligosaccharides-lactic acid
Reduces colonisation and pathogens
Age 3- adult like microbiota
Medication, diet, living environment- affect the
amounts and type of microbiota we have
Broad spectrum antibiotic use-can cause
dysbiosis
C diff affects the colon= arises after recent travel
or antibiotic use
Antibiotic resistance is a issue when treating C diff infections
Broad-spectrum kills off
commensals- fewer to fight
infections and remove noxious
stimuli- therefore, C-diff produes
toxins=injury, neutrophils and
RBCS leak into the epithelial cells.
How do commensal bacteria
contribute to health:
, Outcompete and limit pathogenic species
Degrade toxins to harmless components- for use
Produce vitamins eg vitamin K for clotting factor synthesis
Breakdown non-digestible carbohydrates into small molecules for absorption
Development of GI immune system and establishment of self- tolerance
Short chain fatty acid synthesis
Bacteria ferment non-digestible carbohydrates- short chain fatty acids
Eg acetate, propionate, butyrate
Acetate- cholesterol metabolism and lipogenesis
Propionate-regulates gluconeogenesis and satiety interacting with gut fatty acid
receptors
Butyrate- utilised by colon epithelial cells- suppression of inflammation
High levels of short chain fatty acids= lower risk of obesity and insulin resistance
=reduce risk of diabetes
Ob/Ob microbiota- heterozygous for leptin gene mutation
2 mutations in leptin gene = obesity
When given microbiota to other mice- significant weight gain
High abundance of firmicutes
Healthy gut microbiota Dysbiotic gut microbiota
Low gut permeability High gut permeability
Low endotoxemia High endotoxemia
Low pro-inflammatory cytokines High levels of pro-inflammatory cytokines
High levels of beneficial molecules- eg Low levels of beneficial molecules
short chain fatty acids
High insulin sensitivity Low insulin sensitivity
High levels of adipocity
High levels of obesity
High calorie intake
Environmental factors
Which cause dysbiosis: high fat and sugar diet, stress, antibiotics – predisposed to metabolic
diseases
Which cause symbiosis: healthy diet, lifestyle, prebiotics and probiotics
Prebiotics are special plant fibers that help healthy bacteria grow in your gut.
Probiotics are live bacteria and yeasts
Ileum-payers patches- clusters of T and B cells, follicular DCs and macrophages
Forms a germinal centre
Mucosal immune system must recognise and eliminate pathogens in the presence of non-
pathogenic microbes
What are the anatomical features of germ free mice:
