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Microbiota On Mucosal > L6/7: Microbiota And Health/disease > Flashcards

L6/7: Microbiota And Health/disease Flashcards

1
Q

What are the major phyla of the gut

A

Bacteroidetes, firmicutes

Some actino and proteo (eg ecoli)

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2
Q

How is it murualistic

A

We benefit from them and they benefit from us via dietary fibre

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3
Q

Explain their role in biosynthesis

A

Of key nutrients and vitamins like folate associated with ntd and cancer

Vitamin k

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4
Q

How do bacteroides have an effect on iga

A

They induce exp of aid for class switching and b cell maturation

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5
Q

How do bacteria induce th17 (two ways)

A

Tlr 5 flagellin causes il6 and il23 release

Or

Sfb induce serum amyloid a for th17 differentiation

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6
Q

Why is th17 important for iga responses

A

It increases the cell exp of pigr (transfer of dimric iga across cell into siga)

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7
Q

Which cytokines do bacteria cause release of for b cell dev

A

Tslp

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8
Q

Which phyla are more diverse at genus level

A

Firmicutes eg roseburia, faecalibacterium, Ruminococcus

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9
Q

How are bacteria involved in metabolic disorders like t2d, obesity, atherosclerosis

A

They regulate metabolic pathways in host

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10
Q

Which major scfa imporgant in inducing pyy for satiety and glp1 for insulin secretion

A

Butyrate and proprionate(main one)

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11
Q

How do they do this

A

Act on gpcr41 and 43 on L- enteroendocrine cells

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12
Q

Give example of low bacteria in t2d

A

Roseburia butyrate producing and akkermansia

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13
Q

What sort of Microbiota are associated with dysbiotic effects in t2d and give example

A

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)

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14
Q

How might acetate be obesogenic

A

Substrate for hepatic and adipocyte lipogenesis , cholesterol synthesis and also causes release of ghrelin hormone iincreasing appetite

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15
Q

What do bacteria do to primary bile acids conjugated cholic and chenodeoxycholic acid

A

Deconjugate them via bile salt hydrolases (beh) and de hydroxylate them via bile acid inducing enzymes (bai)

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16
Q

What are they conjugated by usually

A

Taurine or glycine

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17
Q

How is deconjugation important in reducing cvd risk through reducing ldlc

A

It makes them hydrophobic so are lost in faeces meaning more cholesterol needed to converged to bile acids

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18
Q

Explain how meat diets through gut Microbiota metabolism can cause atherosclerotic risk

A

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

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19
Q

What are the secondary bile acids produced by bacteria

A

Lithocholic and deoxycholic acids

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20
Q

Which gut Microbiota metabolite looks like paracetamol and competitively binds to its enzyme to convert it to active form

A

Pcresol

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21
Q

Which enzyme

A

Sulfotransferase sult1a1

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22
Q

Which cardiac drug is inactivated by eggerthella Lenta

A

Digoxin into dihydrodigoxin

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23
Q

How does it stop working

A

Less affinity for na/k ATPase target in heart

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24
Q

Which chemotherapeutic drug can be reactivsted in gut after deconjugation in liver

A

Irinotecan (active chemo compound is called sn-38)

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25
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
26
Give some examples of complex glycans for fibre used by B,f,a,p
Plant wall polysaccharide- xylans resistant starch Fructans polysach or FOS
27
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)
28
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
29
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)
30
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
31
Give an example of a butyrate producing bacterium low in these situations
Clostridium
32
How can butyrate have anti cancer effects
It is a HDAC inhibitor. Can cause hyperacetylstion of apoptotic pathways = dead cancer cels
33
Which scfa act as acetyl donors for dn lipogenesis
Acetate and butyrate
34
How does acetate help colonisation resistance
Lowers ph
35
How can acetate be used to produce more butyrate
Cross feeding on acetate
36
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
37
How do they induce exp of amps in paneth cells
Downstream activation of stat3 txn activator by gpr43 binding
38
Which tj protein is upreg through hif1 through induction by anaeorbic butyrate
Claudin-1
39
How do they increase muc2
Ap1 txn activator allegedly or hdaci
40
What can bacteria metabolise/ferment instead of fibre in high protein low carb diets
Amino acids
41
Give an example of a detrimental metabolite this produces
Hydrogen sulfide which breaks down mucus barrier and also can be converted to thiosulfate then tetrathionate used as an aea by enteropathogens (Also tmao production)
42
Give some other potentially detrimental metabolites which are not beneficial unlike scfa
Ammonia, indolic substrates, branched chain fatty acids
43
L2- Microbiota diversity and influences
D
44
Name some things affecting gut composition
Antibiotics Diet Birth mode Breastfeeding Disease eg Ibd
45
What is lost through c section from mother transfer in vaginal delivery
Bifido and bacteroides
46
What can be transmitted instead from hospital environment
Opportunists eg enterobacteraciae like klebsiella or enterobacter (phylum is proteobac)
47
Give some things more likely in C-section babies
Immune problems eg hypersensitivity, ibd and metabolic problems like diabetes (low butyrate?) ASTHMA!! All associated with proteobac
48
Is the dysbiotic composition known
No
49
What can grow on breast milk hmo best
Bifido infantis or adolescentis
50
Other than hmo what does formula milk also lack which is bad
Antimicrobial lactoferrins Iga from mother
51
What can usually outgrow in formulae milk
Alterations eg increase proteobac like ecoli
52
What are they associated with that bifido is not (negatively associated)
Allergies
53
What happens in fermentation of hmo
Scfa production
54
What can cross feed from hmo or prebiotic inulin-fructans breakdown by bifido
Butyrate producing eg faecalibacterium prausnitzii (firmicutes)
55
Can fmt be done from mother to child after c section to retain normal bacteria
Yes but only done on small samples of babies so far
56
From ff fed mice. Does it show that diversity of Microbiota can ever be regenerated
No. There is chronic loss
57
Why is this bad
Reduced the metabolic potential and immune potential that diverse microbes can have
58
What is a major factor in reducing this diversity
Diet change where not enough dietary fibre or not diverse enough for the cross feeding to happen
59
Give example from the 16s metagenomics study on crohns firmicute composition
43 otu found in gut of healthy vs significant loss of all firmicutes (13 otu) eg clostridia
60
How does butyrate affect proinflam cytokines through nfkb
Blocks degradation of ikb meaning nfkb is txn repressed
61
What other differences between industrialised modern society and traidiotnal has changed Microbiota
Sanitation, antiobiotic use
62
Which types of bacteria have increased which is potentially bad in industrialised
Verrucomicrobia feeding on mucin And bacteroidaceae also feed on mucins
63
Give example of lost cazyme diversity through time in society
Prevotellaceae (fmricutes) are part of the vanish species
64
Changes in diet etc how does this create a lag phase in host adaptation which causes bad microbe-host interactions eg ifnslmation
The body can’t adapt as quick to these changes like Microbiota so end up getting obesity or inflammation etc
65
Rexplain Desai 2016
Ff fed mice showed increase mucin degrades akkermansia and caccae And increased cazymes exp like gh109 for galnac but reduced for plant polysaccharides Increased susceptibility to citrobacter
66
What did glucose fed mice do similarly in dss induced colitis mice
Increased mucin degraders and cazymes because can’t use glucose Showed this excacerbated dss induced colitis
67
Give an example of fmt success story
Used to treat C. difficile infections eg post antibiotics because antibiotics kill it but spores remain in gut Fmt allows to get rid of spores
68
Give an example of a bacteriocin for this
Thurin cd from bacteroides thuringiensis
69
What is probiotics for
Usually live microbes llactobacillus and bifido which can help colonise eg bifido causes cross feeding with butyrate producing ones Also modulate immune responses like lactobacillus gg induces siga in gut response
70
What is currently being added to formula as a prebiotic and what is a challenge to add in
Fos and inulin fructan Challenge is hmo
71
Where can inulin be found
Eg Chicory, garlic
72
Give a gut-brain axis example of how brain modulates the gut neuro immunity and microbe composition
Cortisol regulation through the Hypothalmic-pituitary-adrenal axis = during chronic stress active This can cause gut permeability through tj disruption, reduce bacteroides spp and promote immune activation eg il6 increase and McP-1
73
How can scfa modulate behaviour / satiety/a peptide through the brain
Through L-enteroendocrine release of glp-1 and pyy which act to stimulate feelings of satiety and reduced appetite
74
What positive effect does butyrate also have on the brain
Maintains the bbb integrity
75
How does inflammation in gut through dysbiosis then link to depression
Cytokines travel through vagus nerve and chronically activate the HPA axis which is thought to a cause of chronic stress and depression
76
Which nt can lactobacillus and bifido release having neuromodulatorg effects
Gaba
77
Which cytokines is said to activate hpa but downregulate the gr for negative feedback = chronic stress and depression from gut dysbiosis
Il6
78
Why would as you age show lower diversity overall
Different diets for example
79
Does alpha diversity increase over someone’s lifetime
Yes (this is where within a. Sample you get more diversity)- eg as a baby you’re first colonised with facultative aerobes then at 120 dol change to obligate such as bifido based on milk
80
How does glp-1 act in the pancreas after release by scfa
Reduced b cell apoptosis Insulin release and glucagon decreases = insulin sensitivity (reduced risk of diabetes)
81
Which one is currently being used for diabetes therapy
Glp-1
82
Along with this dysbiosis, which bacteria which could be increased in t2d increases risk and how
Prevotella copri through preference of protein digestion which produces bcaa causing insulin resistance
83
Which other 2 bacterial metabolites can help reduce t2d risk/obesity through glp1 and how
Secondary bile acid production eg lithocholic acid can bind tgr5 and cause release of glp1 Trp metabolite Indole also promotes glp-1 release
84
What are the effects of ammonia and phenol which are by products of aa degradation
Tj disruption and permeability Ammonia also increase pro inflam cytokines like tnfa
85
How does h2s disrupt the mucosal barrier
Disulfide bonds
86
Which aa counteracts the negatives of aa metabolism and how
Trp- produces Indole or Indole derivatives like indole3aldehyde known to reverse colitis through binding ahr and il22 release = mucus formation and amp release
87
What compositional change is associated with ageing
Over bloom of proteo bacteria over reducing firmicutes Likely a combination of reduced complex glycans for example or lifestyle leads to this This then drives feedforwaed loop of inflammation eg through LpS dominant enterobacteriacea which then promotes chronic inflammation = drives expansion of facultative proteobac even more eg via aea nitrate
88
Explain the change of microbes between vaginal and c-section
Vaginal obtain lactobacilli from vagina , bifido and bacteroides C-section are colonised by both skin strep/staph and also NICU opportunists eg enterococcus and klebsiella (associated with nec too)
89
What virulence factor does the likes of klebsiella oxytoca have associated with babies in the infirmary
Tilivalline causing intestinal permeability
90
Within 6-12 months what happens to this difference
The colonisation becomes similar between the 2 except still reduced bacteroides in c-section
91
What gf is present in human milk which blocks tlr4 so has protective effect
Egf
92
Which bifido species are major in hmo breakdown through fucksidases and sialidases
Infantis and bifidum
93
What do bifido produce from hmo/inulin prebiotics which promote cross feeding to butyrate producing eg f prausnitzii
Acetate produced which can be eaten by them to produce butyrate
94
Which other bacteria used in probiotics can also produce acetate and lactic acid to reduce ph for pathogenic
Lactobacilli eg reuteri (also for barrier function through amp and mucus)
95
What are synbiotics
The proposed idea of mixing pre with postbiotics for their food
96
What is the problem with the range of prebiotics used now eg fructan inulin, fos
Soluble so don’t reach the distal colon for a beneficial effect Need to expand
97
How are secondary bile acids (shown in inflammatory dysbiosis to be low in production) anti inflammatory / tolerance inducers
Bind FXR or tgr5 to induce m2 polarisation Also block roryt which stops ilc3 polarisation and it’s downstream inflam effects

Microbiota On Mucosal (22 decks)

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