L6/7: Microbiota And Health/disease Flashcards
What are the major phyla of the gut
Bacteroidetes, firmicutes
Some actino and proteo (eg ecoli)
How is it murualistic
We benefit from them and they benefit from us via dietary fibre
Explain their role in biosynthesis
Of key nutrients and vitamins like folate associated with ntd and cancer
Vitamin k
How do bacteroides have an effect on iga
They induce exp of aid for class switching and b cell maturation
How do bacteria induce th17 (two ways)
Tlr 5 flagellin causes il6 and il23 release
Or
Sfb induce serum amyloid a for th17 differentiation
Why is th17 important for iga responses
It increases the cell exp of pigr (transfer of dimric iga across cell into siga)
Which cytokines do bacteria cause release of for b cell dev
Tslp
Which phyla are more diverse at genus level
Firmicutes eg roseburia, faecalibacterium, Ruminococcus
How are bacteria involved in metabolic disorders like t2d, obesity, atherosclerosis
They regulate metabolic pathways in host
Which major scfa imporgant in inducing pyy for satiety and glp1 for insulin secretion
Butyrate and proprionate(main one)
How do they do this
Act on gpcr41 and 43 on L- enteroendocrine cells
Give example of low bacteria in t2d
Roseburia butyrate producing and akkermansia
What sort of Microbiota are associated with dysbiotic effects in t2d and give example
Clostridium eg and prevotella Copri
Ef involved in increase glucose uptake from gut and branched aa which cause insulin resistance
(They prefer protein utilisation over glycans)
How might acetate be obesogenic
Substrate for hepatic and adipocyte lipogenesis , cholesterol synthesis and also causes release of ghrelin hormone iincreasing appetite
What do bacteria do to primary bile acids conjugated cholic and chenodeoxycholic acid
Deconjugate them via bile salt hydrolases (beh) and de hydroxylate them via bile acid inducing enzymes (bai)
What are they conjugated by usually
Taurine or glycine
How is deconjugation important in reducing cvd risk through reducing ldlc
It makes them hydrophobic so are lost in faeces meaning more cholesterol needed to converged to bile acids
Explain how meat diets through gut Microbiota metabolism can cause atherosclerotic risk
Choline and carnitine from red meat can be metabolised into tma by Microbiota
Then by hepatic host fmo they will oxidise it into tma-oxide (Tmao)
This upregulates scavenehrr ldl receptors on macrophages and also blocks cholesterol conversion into bile acids = increased ldlc and plaques
What are the secondary bile acids produced by bacteria
Lithocholic and deoxycholic acids
Which gut Microbiota metabolite looks like paracetamol and competitively binds to its enzyme to convert it to active form
Pcresol
Which enzyme
Sulfotransferase sult1a1
Which cardiac drug is inactivated by eggerthella Lenta
Digoxin into dihydrodigoxin
How does it stop working
Less affinity for na/k ATPase target in heart
Which chemotherapeutic drug can be reactivsted in gut after deconjugation in liver
Irinotecan (active chemo compound is called sn-38)
How and why has this led to inhibitors being administered with irinotecan to block toxicity
B glucoronidases and because it’s toxic
Screened for inhibitors of these enzymes
Give some examples of complex glycans for fibre used by B,f,a,p
Plant wall polysaccharide- xylans
resistant starch
Fructans polysach or FOS
Give an example of cross feeding on xylans
B ovatus can use complex xylans and then metabolise them into simple xylans used by bifido adolescentis (can’t grow separately)
What would happen if butyrate wasn’t present for b oxidation
Colonocytes needs to get energy from glycolysis which releases a lot of o2 making the gut aerobic which is bad
How is this bad and allows salmonella typhimurium
They can use oxygen as a respiratory electron acceptor for growth through their cytochrome bd oxidase they have
(Mutualists don’t)
How does ppary have to do with this
Activated by butyrate as it is an activator of b oxidation
Without ppary inos No synthase can be released and conversion into nitrate can be used by salmonella again for nitrate resp = outcompete
Give an example of a butyrate producing bacterium low in these situations
Clostridium
How can butyrate have anti cancer effects
It is a HDAC inhibitor. Can cause hyperacetylstion of apoptotic pathways = dead cancer cels
Which scfa act as acetyl donors for dn lipogenesis
Acetate and butyrate
How does acetate help colonisation resistance
Lowers ph
How can acetate be used to produce more butyrate
Cross feeding on acetate
How do all 3 cause antiinflammation pathways
Proprionate is HDAC 6 and 9 inhibitor which induces fox p3 exp
All 3 binds gpcr43 on tregs fox p3+ surface and activates them and causes secretion if il10
Il10 induces m1 to m2 shift which is antiinflam and also stops antigen presentation
How do they induce exp of amps in paneth cells
Downstream activation of stat3 txn activator by gpr43 binding
Which tj protein is upreg through hif1 through induction by anaeorbic butyrate
Claudin-1