L15: Ibd, Host And Microbiota

Question 1

Where does crohns affect

Answer 1

Any part of the gi tract from oral to rectum

Question 2

What are skip lesions in crohns

Answer 2

Areas of non inflamed then inflamed again

Question 3

What does transmural inlfammation in crohns mean

Answer 3

All layere eg from mucosa to serosa. Forms strictures and fistulae

Question 4

What are strictures and fistulae

Answer 4

Strictures are narrowing of gi tract due to chronic inflammation and scarring process

Fistulae are tunnels connecting 2 tissues/ organs which dont usually. Forming new passages for leakage eg of faeces

Question 5

What can fistulae form

Answer 5

Abscesses

Question 6

How does uc compare

Answer 6

Only in colon, no skip lesions, from caecum all the wag to rectum usually

More superficial inflammation to mucosa

Question 7

Where does crohns usually occur

Answer 7

Terminal ileum

Question 8

Give some extra intestinal symptoms

Answer 8

Inflammation in eye, enteropsthic arthritis

Question 9

Where does uc husallt start

Answer 9

Rectum

Question 10

Whats the precalence in %

Answer 10

0.78 in 2018 but can increase to 1% in 2028

Question 11

Give some fsctors of prevalence

Answer 11

Westernised diet, usually youngner onset (20-40), environment eg stress, smoking ,

Question 12

What % have a relapse with uc

Answer 12

90%

Question 13

What do early relapses indicate

Answer 13

Worse disease course

Question 14

Who usually gets uc

Answer 14

Yojnger males

Question 15

How many people usually indergo surgery eith crohns agter 10 years

Answer 15

50%

Question 16

What are taken all the time whth these conditions

Answer 16

Corticosteroides

Question 17

What haplens with crohns overtime so needs to be treated fast (target wbc)

Answer 17

Fistulae and strictures

Question 18

How many genes are related to ibd

Answer 18

300 genes eg nos in inflammation upreg

Question 19

What causes the intiial inflammation

Answer 19

Impaired barriers, dysbiosis, causing microbe interaction eith inflam cells

Question 20

Which article discusses cytokines in ibd

Answer 20

Neurath 2014

Question 21

Which types of genes were involved in ibd

Answer 21

Amps, chemokines, cyotkines

Question 22

Which ibd has increased il-1b wg from inflammasome causing inflamation via granulochtes and th17

Answer 22

Crohns

Question 23

Why was increased il18 important in crohns

Answer 23

Induces macrophages which secrete inflammatory ifny

Question 24

How is il6 important in ibd

Answer 24

Platelet increase, reduced mucosal T death= inflammation bc induces th2

Question 25

Which ibd is seen high th17

Answer 25

Both uc and crohns

Question 26

Why is th1 seen crohns

Answer 26

Too much ifny and tnf release = inflammation

Question 27

What would be the resolution to inflammatjon but not presenf eg due to lack of fibre

Answer 27

Ra, tgfb ——> increase in dc producing tregs

Question 28

Does il10 block il1b inflammasome

Answer 28

Yes

Question 29

Why are ifna and b good for ibd

Answer 29

Help regenrstion of epi cells, induce t regs

Question 30

What do microbiota do to do with ifna and b

Answer 30

Increase its release from apc by binding tlr9

Question 31

Which gene is upreg in ibd blockign tgf b and therefore tregs

Answer 31

Smad7 signalling protein

Question 32

What sorts of things do you need to look at when diagnosing ibd

Answer 32

``` Hereditary factors (3%) Nsaids can dause acute symptoms Smoking history Travel Gastroenteritis which triggers ibd Extra intestinal manifeststions ```

Question 33

Which eim are present (neurath 2019)

Answer 33

Iritis, conjunctivitis, thrombosis, arthritis, liver damage

Question 34

What blood markeds are looked for

Answer 34

Crp creaxtive protein inflam marker Full blood count fbc = anemic Liver functioning trsts /LFT

Question 35

How is it diagnosed

Answer 35

Capsule endoscopy, colonsocopy and biopsy, mri, ct

Question 36

What is lost in mucosa with ibd

Answer 36

Mucosa, crytps, too mant inflam cells nesr

Question 37

Why can too high th2 eg from il6 and il4 cause ibd

Answer 37

Attracts eosinophils, basophils, mast cells

Question 38

What type of inflammation do th1 allow

Answer 38

Monocytic which secrete cytokines like tnf and ifny

Question 39

What 2 approaches to therapt are there

Answer 39

Step up (gentle to immunosuppressants eg methotrexate to biologics to surgery) Step doen (biologica to surgery)

Question 40

Whixh med is used for uc inly

Answer 40

5 ASA

Question 41

What types of biologics are there

Answer 41

Anti a4:b7, anti tnf, anti il12, anti 23

Question 42

Which article discusses microbiota and ibd involvemnet

Answer 42

Ni et al 2017

Question 43

Which tpyes of bacteria are reduced in ibd eg due to wrsternised diet

Answer 43

Firmicutes

Question 44

Why do proteobacteria like ecoli increase

Answer 44

Inflammation is oxidstive and they are aerotolerant

Question 45

What else does inflammation do to allow outgrowth of commensala

Answer 45

Aea eg via nos = nitrate resp by ehec

Question 46

What is reduced due ti lacj of commensala in ibd

Answer 46

Farnesoid x activation by bile acids (which is anti tnf)

Question 47

Which yeast are seen to grow in crohns brcause of lack of commenslas and what happens because of it

Answer 47

Candida Further acticates apc and eg th1 pathway, tnf etc

Question 48

Why is ifny release so bad for dysbiosis

Answer 48

Allows release of NO and ROS No for nitrate resp and ros for tetrathionate

Question 49

What is one god thing anout inflammasome till it gets too much

Answer 49

Epithelial regeneration

Question 50

Why is it impaired jn ibd

Answer 50

Mutation in gene for jnflammasome

Question 51

Which cytokine from microbiota allows diff of th17 and ilc3 = chronic inflammation

Answer 51

Il23

Question 52

Where are tlr and nod

Answer 52

Innate, paneth and epi cells

Question 53

Which antibody blocks colitogenic pathogens

Answer 53

Iga

Question 54

Which types of th17 mutstions sre in ibd

Answer 54

Il23 r

Question 55

Which other types of genes are mutated which increase activity or decrewase

Answer 55

Hla, Barrier genes defecting it wg ecm1 Autophagy

Question 56

What is autophagy for

Answer 56

Recycle cellular organeles and degradation of ic pathogens

Question 57

Which polymorphisms commin with autophagy in ibd

Answer 57

Atg16L1, irgm, LRRK2

Question 58

What does autophaggy usually alow release of from paneth cells

Answer 58

Amps

Question 59

What does polymorphism do to cytokines eg in atg16L1, lrrk2 and irgm

Answer 59

Alter them so less amp but il1b and il 18 released instead from paneth

Question 60

What types of pathogens are killed by autophagy

Answer 60

Salmonella, ehec, mycobacterium tb

Question 61

Whcih receptors regulate autophagy

Answer 61

Prr

Question 62

Which article discusses autophagy snd ibd

Answer 62

Levine 2011

Question 63

What did atg16L1 reduce

Answer 63

Amp

Question 64

How does irgm cause franumolas in crohns if defective

Answer 64

Usuallt allows clearing of mycobac tb which if not cleared causes granulomas

Question 65

How many nod2 polymorphisms seen in crohns

Answer 65

3

Question 66

Where is nod2 and what does it sense

Answer 66

Mac, epi, dc, paneth, neutrophils Finds bscterial peptidoglycan

Question 67

What type of nfkb cytokines released by nod2 which see loss in crohns and granuloma formation

Answer 67

Il1b and il8 and il10

Question 68

Hoe many firmicute otu seen in people without crohns vs with

Answer 68

43 vs 13

Question 69

Why is asca a marker of crohns

Answer 69

Increased sach cer and candida

Question 70

Which firmicute seen in lower numbers which activates release of il10

Answer 70

Faecailbacterium prausnitzii

Question 71

Which ibd has a risk of smokingand what does smokint do

Answer 71

Crohns Reduces diversity Refuces actinobacteria like collinsella and firmicutes Worse outcome and recurrence

Question 72

What is an anal fistula and how is it resolved

Answer 72

A tunnel from bowek to the skin nesr anus whoch gives farces another route forming abscesses Need surgery to close tunnel

Question 73

Stoma surgery is an alt. Whag is it

Answer 73

Opening of abdomen to dicert faeces and urine away from rectum and collected in stomal bag

Question 74

What are ileoanal pouch surgeries

Answer 74

Anal canal is attached to the ileum (anastomoses formed) and rectum/ colon removed

Question 75

What is it callrd when pocuhes get inflammed and what antibiotics used

Answer 75

Pouchitis Ciprofloxacin and metronidazole

Question 76

What is pouchitis due to microbiota

Answer 76

Low roseburia and blautia vs increased b vulgatus

Question 77

Why is fmt not a good treatment

Answer 77

Overrime you go bsck tk the baseline microbiota

Question 78

Shich diet product increased colitis

Answer 78

Casein from milk

Question 79

Which fibre reduced colitis

Answer 79

Psyllium from seeds

Question 80

Why does akkermwnsia reduce ivd even if it erodes mucus

Answer 80

It produces alotnof scra in return

Question 81

Does fmt composition affect outcome eg for anti pd1 therapy

Answer 81

Yes

Question 82

Which microbiota worked for anti pd1 vs which didnt for antitumour effects

Answer 82

Bifido and akkermansia were good eg produced cd8 but bacteroidales were weak t reg responses