L15: Ibd, Host And Microbiota Flashcards
Where does crohns affect
Any part of the gi tract from oral to rectum
What are skip lesions in crohns
Areas of non inflamed then inflamed again
What does transmural inlfammation in crohns mean
All layere eg from mucosa to serosa. Forms strictures and fistulae
What are strictures and fistulae
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
What can fistulae form
Abscesses
How does uc compare
Only in colon, no skip lesions, from caecum all the wag to rectum usually
More superficial inflammation to mucosa
Where does crohns usually occur
Terminal ileum
Give some extra intestinal symptoms
Inflammation in eye, enteropsthic arthritis
Where does uc husallt start
Rectum
Whats the precalence in %
0.78 in 2018 but can increase to 1% in 2028
Give some fsctors of prevalence
Westernised diet, usually youngner onset (20-40), environment eg stress, smoking ,
What % have a relapse with uc
90%
What do early relapses indicate
Worse disease course
Who usually gets uc
Yojnger males
How many people usually indergo surgery eith crohns agter 10 years
50%
What are taken all the time whth these conditions
Corticosteroides
What haplens with crohns overtime so needs to be treated fast (target wbc)
Fistulae and strictures
How many genes are related to ibd
300 genes eg nos in inflammation upreg
What causes the intiial inflammation
Impaired barriers, dysbiosis, causing microbe interaction eith inflam cells
Which article discusses cytokines in ibd
Neurath 2014
Which types of genes were involved in ibd
Amps, chemokines, cyotkines
Which ibd has increased il-1b wg from inflammasome causing inflamation via granulochtes and th17
Crohns
Why was increased il18 important in crohns
Induces macrophages which secrete inflammatory ifny
How is il6 important in ibd
Platelet increase, reduced mucosal T death= inflammation bc induces th2
Which ibd is seen high th17
Both uc and crohns
Why is th1 seen crohns
Too much ifny and tnf release = inflammation
What would be the resolution to inflammatjon but not presenf eg due to lack of fibre
Ra, tgfb ——> increase in dc producing tregs
Does il10 block il1b inflammasome
Yes
Why are ifna and b good for ibd
Help regenrstion of epi cells, induce t regs
What do microbiota do to do with ifna and b
Increase its release from apc by binding tlr9
Which gene is upreg in ibd blockign tgf b and therefore tregs
Smad7 signalling protein
What sorts of things do you need to look at when diagnosing ibd
Hereditary factors (3%) Nsaids can dause acute symptoms Smoking history Travel Gastroenteritis which triggers ibd Extra intestinal manifeststions
Which eim are present (neurath 2019)
Iritis, conjunctivitis, thrombosis, arthritis, liver damage
What blood markeds are looked for
Crp creaxtive protein inflam marker
Full blood count fbc = anemic
Liver functioning trsts /LFT
How is it diagnosed
Capsule endoscopy, colonsocopy and biopsy, mri, ct
What is lost in mucosa with ibd
Mucosa, crytps, too mant inflam cells nesr
Why can too high th2 eg from il6 and il4 cause ibd
Attracts eosinophils, basophils, mast cells
What type of inflammation do th1 allow
Monocytic which secrete cytokines like tnf and ifny
What 2 approaches to therapt are there
Step up (gentle to immunosuppressants eg methotrexate to biologics to surgery)
Step doen (biologica to surgery)
Whixh med is used for uc inly
5 ASA
What types of biologics are there
Anti a4:b7, anti tnf, anti il12, anti 23
Which article discusses microbiota and ibd involvemnet
Ni et al 2017
Which tpyes of bacteria are reduced in ibd eg due to wrsternised diet
Firmicutes
Why do proteobacteria like ecoli increase
Inflammation is oxidstive and they are aerotolerant
What else does inflammation do to allow outgrowth of commensala
Aea eg via nos = nitrate resp by ehec
What is reduced due ti lacj of commensala in ibd
Farnesoid x activation by bile acids (which is anti tnf)
Which yeast are seen to grow in crohns brcause of lack of commenslas and what happens because of it
Candida
Further acticates apc and eg th1 pathway, tnf etc
Why is ifny release so bad for dysbiosis
Allows release of NO and ROS
No for nitrate resp and ros for tetrathionate
What is one god thing anout inflammasome till it gets too much
Epithelial regeneration
Why is it impaired jn ibd
Mutation in gene for jnflammasome
Which cytokine from microbiota allows diff of th17 and ilc3 = chronic inflammation
Il23
Where are tlr and nod
Innate, paneth and epi cells
Which antibody blocks colitogenic pathogens
Iga
Which types of th17 mutstions sre in ibd
Il23 r
Which other types of genes are mutated which increase activity or decrewase
Hla,
Barrier genes defecting it wg ecm1
Autophagy
What is autophagy for
Recycle cellular organeles and degradation of ic pathogens
Which polymorphisms commin with autophagy in ibd
Atg16L1, irgm, LRRK2
What does autophaggy usually alow release of from paneth cells
Amps
What does polymorphism do to cytokines eg in atg16L1, lrrk2 and irgm
Alter them so less amp but il1b and il 18 released instead from paneth
What types of pathogens are killed by autophagy
Salmonella, ehec, mycobacterium tb
Whcih receptors regulate autophagy
Prr
Which article discusses autophagy snd ibd
Levine 2011
What did atg16L1 reduce
Amp
How does irgm cause franumolas in crohns if defective
Usuallt allows clearing of mycobac tb which if not cleared causes granulomas
How many nod2 polymorphisms seen in crohns
3
Where is nod2 and what does it sense
Mac, epi, dc, paneth, neutrophils
Finds bscterial peptidoglycan
What type of nfkb cytokines released by nod2 which see loss in crohns and granuloma formation
Il1b and il8 and il10
Hoe many firmicute otu seen in people without crohns vs with
43 vs 13
Why is asca a marker of crohns
Increased sach cer and candida
Which firmicute seen in lower numbers which activates release of il10
Faecailbacterium prausnitzii
Which ibd has a risk of smokingand what does smokint do
Crohns
Reduces diversity
Refuces actinobacteria like collinsella and firmicutes
Worse outcome and recurrence
What is an anal fistula and how is it resolved
A tunnel from bowek to the skin nesr anus whoch gives farces another route forming abscesses
Need surgery to close tunnel
Stoma surgery is an alt. Whag is it
Opening of abdomen to dicert faeces and urine away from rectum and collected in stomal bag
What are ileoanal pouch surgeries
Anal canal is attached to the ileum (anastomoses formed) and rectum/ colon removed
What is it callrd when pocuhes get inflammed and what antibiotics used
Pouchitis
Ciprofloxacin and metronidazole
What is pouchitis due to microbiota
Low roseburia and blautia vs increased b vulgatus
Why is fmt not a good treatment
Overrime you go bsck tk the baseline microbiota
Shich diet product increased colitis
Casein from milk
Which fibre reduced colitis
Psyllium from seeds
Why does akkermwnsia reduce ivd even if it erodes mucus
It produces alotnof scra in return
Does fmt composition affect outcome eg for anti pd1 therapy
Yes
Which microbiota worked for anti pd1 vs which didnt for antitumour effects
Bifido and akkermansia were good eg produced cd8 but bacteroidales were weak t reg responses
