crc microbiome

Question 1

name the alpha bug?

Answer 1

fusobacterium nucleatum

Question 2

how does it work?

Answer 2

fusobacterium nucleuatum bacteria produces fadA adhesins which binds to ecadherin and activates signalling pathays in CRC pathiogenesis, such as beta catenin and wnt signalling

Question 3

raisch 2016 review

Answer 3

enriched f bacterium in CRC which was also increased in adenomas vs controls thus perhaps in early stage involvement
the hypothesis via fadA adhesion was shown in mouse studies with 80% of samples containing F.N In APC preidosped mice

increase in myeloid cells ad tumour multicipicty

msi and cpy island finluenced by microbiota

Question 4

ecoli

Answer 4

breaks double stranded DNA through polyketide synthesis using genotoxin colibactin promotes cell proliferation

Question 5

bacteriodes fragilis

Answer 5

non enterotoxgenic strain inhibits IL17

entertoxigenic strain promotes 1L7 and th17 and STAT3 activation for colonic hyperplasia

Question 6

s.galliolyticus

Answer 6

cox 2 mediator inflammatory response

Question 7

e.faceleais

Answer 7

free radical and superoxide production

Question 8

diet raisch 2016

Answer 8

high protein, low fibre diet stimulates production of microbials that increase toxic metabolites which decrease cancer protection metabolites

Question 9

driver passenger hypothesis

Answer 9

drivers initate tumourgenesis early development 
passenger bacteria thrive on cancer
outcompete drive bacteria
take over 
colonic tumourgenesis progession

Question 10

findings associated with F.N

Answer 10

Mina et al found that increase in FN was associated with poorer prognosis
also findings that increase was associated with f.n and crc features

Question 11

marchesi paper

Answer 11

diagram showing interaction between microbiota
environemtal factors such as diet, smoking, alcohol drugs which influence CRC development
oncogenic pre-conditioning
allows understand for therapy potential new target to improve microbiome diversity and perhaps FT

Question 12

metholodgy problems

Answer 12

no consideration of bowel preparation
reduced bacterial load in studies
but restored within 2 weeks
jalanka

Question 13

key findings of riasch 2k16

Answer 13

[1] msi and cpg island
[2] low carb high protein diet
[3] fadahesion shown in mice studies apc predisopsed - 80% f.n
[4] enriched crc and adenoma with f.n perhaps early development

Question 14

biomarkers

Answer 14

increase in choline and faecal bile acid

decrease inn butyrate