Lecture 10: Microbiome 2 Flashcards
What is dysbiosis?
An unhealthy, unbalanced, disturbed microbiome
What percentage of metabolites in the mammalian blood flow are of bacterial origin?
10%
What is unclear?
What constitutes a healthy or unbalanced microbiome
What was thought for a long time about birth? What type of transmission is involved and how did Jiminez et all prove this happened?
That we are born sterile. Vertical transmission. Fed pregnant mice with labelled bacteria and recovered it from the meconium of pups so the bacteria had colonised the mouse embryos
What is the microbiome of babies delivered vaginally dominated by? How does this differ in babies delivered by C section?
Lactobacillus. C section have microbiota more similar to the skin community (not necessarily of mother) which is dominated by staphylococci.
What is delayed in C section babies but what happens?
Firmicutes and bacteriodetes but they catch up eventually.
What is there some evidence about C section babies?
More likely to have asthma, inflammatory bowel disease and diabetes
What does increased oestrogen do and what is different in preterm infants?
Causes increase in lactobacillus species which helps establish healthy gut microbiome in neonate. Preterm infants lack the good bifidobacterium and lactobacillus, having dominance of proteobacteria.
What does breast milk contain?
microbes, metabolites, immunoglobins, immune cells as well as cytokines
What do we all have a very low level of?
Septicaemia
How does the microbiota diversify?
100 species at birth to over 700 species between 6-12 months
What are the early colonisers replaced by?
Bacteria from the external environment
What is each dietary change parallelled with?
Changes in the microbiota and a predominance of genes specialised towards microbial digestion of that diet
What have some studies found in adolescents?
Higher levels of clostridium and bifidobacteria
What was the gut microbiota of healthy children between 9-14 living in Bangladeshi slum and US upper-middle class community?
Bangladesh had more diverse species and lower bacteriodes.
Describe the reasons for and against nature/nurture of the microbiome
gut microbiome more similar between family members but strong role for environment.
Mouse studies have shown changing a single host gene has great effect on gut microbiome eg MEFV gene with an unusual allele gives you a hereditory disease called Familial Mediterranean Fever and people with this have lower microbial diversity.
What factors affect dysbiosis?
Changes in diet eg large amounts of animal fats and proteins. Overuse of antibiotics. Elimination of beneficial organisms that form mutualises with bacteria eg nematode worms can promote growth of good bacteria.
What could gut dysbiosis in the developed world account for?
allergies, autoimmune and inflammatory disorders
What can gut dysbiosis causing inflammation result in?
Bacteria entering through the inflammed lining which can cause an immune response.
What is the hygeine hypothesis?
Lack of early childhood exposure to symbiotic microorganisms and parasites increases susceptibility to chronic inflammatory diseases by suppressing the development of the immune system. eg asthma, depression, multiple sclerosis.
What receptors are key receptors of the innate immune response to bacterial antigens?
Toll like receptors (TLRs)
What does TLR5 mediate a response to? How is this relevant to flu?
Flagellin which is a constituent of flagella. It is an adjuvant so boosts the immune response to other antigens.
What did knock out TLR5 mice show?
Lower levels of antibodies after receiving the flu vaccine.
What is increased and decreased in the elderly?
Facultitive anaerobes and bifidobacteria
How has C.elegans been used to show that the gut microbiome can influence the rate of ageing?
C.elegans grown with E.coli food source.
1) In young worms the bacteria are borken down after ingestion but they colonise the gut of older worms.
2) diffusible molecules such as metabolites and small RNAs can prolong or decrease the lifespan of the nematode. NO can’t be synthesised by the C.elegans as they don’t have NO synthase as they get this from the gut microbiome, Bacillus subtillis.
3) mcRNA DsrA interferes with the expression of the worm gene F42G9.6 which is involved in slowing ageing and increasing longevity. Feeding worms with E.coli deficient in mcRNA DsrA increases their lifespan.
What can metformin, prescribed for type 2 diabetes do?
Reduces folic acid production and methionine and increases lifespan in rodents.
What might the microbiome influence?
Mood, cognition and pain
Why might the microbiome be used to treat CNS disorders?
There is bidirectional communication between CNS and GI tract. Is responsible for satiety, hunger and digestive function
How does communication between the brain and gut occur?
via neuronal routes, humoural signalling molecules and hormonal components.
What are impairments in brain gut axis signalling responsible for?
gut inflammation, abdominal pain syndromes, eating disorders, stress and altered behaviour.
Which nerve is responsible for bidirectional communication?
Vagus nerve
Where isn 95% of serotonin found and what does it do here?
In the gut. Regulates GI secretion, pain perception, motility.
What do SSRIs do?
Alter function of serotonin. Can alleviate symptoms of irritable bowel disease and depression.
What happens to germ free mice in stressful environments?
They show decreased anxiety which is dangerous and colonisation with normal microbiota reverses this effect.
