Lecture 10: Microbiome 2

Question 1

What is dysbiosis?

Answer 1

An unhealthy, unbalanced, disturbed microbiome

Question 2

What percentage of metabolites in the mammalian blood flow are of bacterial origin?

Answer 2

10%

Question 3

What is unclear?

Answer 3

What constitutes a healthy or unbalanced microbiome

Question 4

What was thought for a long time about birth? What type of transmission is involved and how did Jiminez et all prove this happened?

Answer 4

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

Question 5

What is the microbiome of babies delivered vaginally dominated by? How does this differ in babies delivered by C section?

Answer 5

Lactobacillus. C section have microbiota more similar to the skin community (not necessarily of mother) which is dominated by staphylococci.

Question 6

What is delayed in C section babies but what happens?

Answer 6

Firmicutes and bacteriodetes but they catch up eventually.

Question 7

What is there some evidence about C section babies?

Answer 7

More likely to have asthma, inflammatory bowel disease and diabetes

Question 8

What does increased oestrogen do and what is different in preterm infants?

Answer 8

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.

Question 9

What does breast milk contain?

Answer 9

microbes, metabolites, immunoglobins, immune cells as well as cytokines

Question 10

What do we all have a very low level of?

Answer 10

Septicaemia

Question 11

How does the microbiota diversify?

Answer 11

100 species at birth to over 700 species between 6-12 months

Question 12

What are the early colonisers replaced by?

Answer 12

Bacteria from the external environment

Question 13

What is each dietary change parallelled with?

Answer 13

Changes in the microbiota and a predominance of genes specialised towards microbial digestion of that diet

Question 14

What have some studies found in adolescents?

Answer 14

Higher levels of clostridium and bifidobacteria

Question 15

What was the gut microbiota of healthy children between 9-14 living in Bangladeshi slum and US upper-middle class community?

Answer 15

Bangladesh had more diverse species and lower bacteriodes.

Question 16

Describe the reasons for and against nature/nurture of the microbiome

Answer 16

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.

Question 17

What factors affect dysbiosis?

Answer 17

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.

Question 18

What could gut dysbiosis in the developed world account for?

Answer 18

allergies, autoimmune and inflammatory disorders

Question 19

What can gut dysbiosis causing inflammation result in?

Answer 19

Bacteria entering through the inflammed lining which can cause an immune response.

Question 20

What is the hygeine hypothesis?

Answer 20

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.

Question 21

What receptors are key receptors of the innate immune response to bacterial antigens?

Answer 21

Toll like receptors (TLRs)

Question 22

What does TLR5 mediate a response to? How is this relevant to flu?

Answer 22

Flagellin which is a constituent of flagella. It is an adjuvant so boosts the immune response to other antigens.

Question 23

What did knock out TLR5 mice show?

Answer 23

Lower levels of antibodies after receiving the flu vaccine.

Question 24

What is increased and decreased in the elderly?

Answer 24

Facultitive anaerobes and bifidobacteria

Question 25

How has C.elegans been used to show that the gut microbiome can influence the rate of ageing?

Answer 25

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.

Question 26

What can metformin, prescribed for type 2 diabetes do?

Answer 26

Reduces folic acid production and methionine and increases lifespan in rodents.

Question 27

What might the microbiome influence?

Answer 27

Mood, cognition and pain

Question 28

Why might the microbiome be used to treat CNS disorders?

Answer 28

There is bidirectional communication between CNS and GI tract. Is responsible for satiety, hunger and digestive function

Question 29

How does communication between the brain and gut occur?

Answer 29

via neuronal routes, humoural signalling molecules and hormonal components.

Question 30

What are impairments in brain gut axis signalling responsible for?

Answer 30

gut inflammation, abdominal pain syndromes, eating disorders, stress and altered behaviour.

Question 31

Which nerve is responsible for bidirectional communication?

Answer 31

Vagus nerve

Question 32

Where isn 95% of serotonin found and what does it do here?

Answer 32

In the gut. Regulates GI secretion, pain perception, motility.

Question 33

What do SSRIs do?

Answer 33

Alter function of serotonin. Can alleviate symptoms of irritable bowel disease and depression.

Question 34

What happens to germ free mice in stressful environments?

Answer 34

They show decreased anxiety which is dangerous and colonisation with normal microbiota reverses this effect.