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Z MD1 GI block > Microbiota > Flashcards

Flashcards in Microbiota Deck (73)
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predominance of gram positive and gram negative bacteria in different places of the body

throat, skin and vagina - predominantly gram positive
gut - predominantly gram negative


predominant phyla of the gut

Bacteroidetes and Firmicutes
then Actinobacteria
Proteobacteria relatively rare


are the gut bacteria predominantly anaerobic or aerobic

anaerobic - 99.9%


what proportion of bacteria of the microbiota are shared between twins



the genes provided by the microbiota contribute to what

- metabolism (carbohydrates, vitamin metabolism/biosynthesis, energy, drugs)
- development
- the immune system
- protection against enteropathogens


what 6 factors can influence the gut bacteria

- mode of delivery
- age
- diet
- antibiotics
- genetics and environment
- chronic inflammation


how does the mode of birth delivery influence the microbiota

-vaginal delivery is associated with rapid acquisition of Firmicutes and Bifidobacteria
- caesarian birth is associated with delayed microbiota development with restricted diversity, and start off with a higher than normal proportion of Protobacteria


what changes in the microbiota are seen over the first few months of life

- initially - microbiota are relatively limited with predominantly Firmicutes and a little bit of proteobacteria involved in lactose breakdown
- 2-3 months - bacteria changes to get used to breaking down plant based food


what types of diets can influence the microbiota

- high fat/low fibre
- low fat/high fibre
- animal based
- plant based


how does animal based diets alter the microbiota

decreases the levels of bacteria that metabolise dietary plant polysaccharides and increase levels of bile-tolerant bacteria (Bacteroides)


Which phyla of bacteria are bile resistant



which antibiotic has long term effects on the gut microbiota?

vancomycin - gut microbiota dont go back to original


2 mechanisms for gut microbiota playing a role in nutrition

- directly supply nutrients from dietary substances (as we dont have the genes to metabolise these substrates)
- alter metabolic machinery of host cells


which dietary substances do the microbiota directly supply us

vitamin B2, vitamin K, biotin, folate


how do microbiota alter metabolic machinery of host cells

- induce changes in host genes involved in carbohydrate and lipid metabolism --> contribute to adiposity
- maintain enterocyte differentiation and function by producing SCFA from undigestible carbohydrates
- induce changes in host genes affecting angiogensis by producing SCFA


what do the microbiota do to carbohydrates

break down lactose, cellulose, mucins --> short chain fatty acids


how do the microbiota affect bile acids

dehydroxylation of cholic acid in the gut --> metabolises this to desoycholic acid - allows resorption back into the liver via the enterohepatic circulation


which amino acids do microbiota especially metabolise for us

lysine and threonine


what is MALT

mucosa-associated lymphoid tissue


what are the lymphoid tissue in the gut

- isolated lymphoid follicles in the large and small intestine
- Peyers patches in the small intestine - ileum
- Intraepithelial lymphocytes in the LP


what is the role for ILFs and Peyers patches in the gut

sites for induction of T and B cell activation


innate defences of the gut in general

- peristalsis
- acid
- mucous layer/glycocalyx
- enterocytes
- innate lymphocytes
- mechanisms for "controlled" antigen access


explain the mucous layer of the gut

associated with the enterocytes - act as a molecular sieve, so the commensals held at "arms length"


How do enterocytes contribute to innate defences

- barrier - tight epithelial junctions
- regular replacement of enterocytes
- secrete immunomodulatory cytokines and chemokines
- paneth cells secrete antimicrobial factors


how do goblet cells contribute to innate defenses

secrete mucins, lysozyme and lactoferrin - inhibiting the growth of micro-organisms


what are the innate lymphoid cells of the gut

lymphoid tissue inducer cells
intraepithelial lymphocytes (IELs)
NK cells


what do lymphoid tissue inducer cells do

stimulate recruitment of DCs, T and B cells to peyers patches and ILFs


Role of IL22 in innate gut immunity

enhances antimicrobial defence and epithelial repair and barrier integrity


what is special about the macrophages of the gut

they are HYPOresponsive to TLR signalling - hard to stimulate them


where are M cells located

directly over the sites of organised lymphoid aggregates


structure of M cells

possess a folded luminal surface (no villi)
lack a thick glycocalyx
dont secrete mucus
(microbial access easier)


function of M cells

deliver antigens directly to the cells in organised lymphoid aggregates


function of DCs in the gut

sample antigen from the intestinal mucosa and induce a variety of T cell differentiation pathways


how do DCs sample antigen from the intestinal mucosa

- directly (put there processes through the tight junctions between enterocytes --> lumen)
- indirectly (delivered by goblet cells or M cells)


what are the 2 main T cell differentiation pathways induced by DCs in the gut

1. in the steady state - induce Treg cells (via TGF-beta) and Th2 --> quite suppressive cytokines
2. under inflammatory conditions - may induce Th1 and Th17


Main isotype switching of the gut and how

IgA via TGF-beta signal 3


how do T and B cells find there way to mucosal tissue

DCs induce mucosal epithelial addressin alpha4beta7 on activated T and B lymphoyctes --> bind the MAdCAM1 integrin on vascular endothelial cells of all mucosal surfaces and chemokine receptors for the lamina propria


What happens when activated T and B cells enter the lamina propria

- activate B cells --> predominantly IgA
- CD4 T cells (either regulatory Treg/Th2 in steady state or inflammatory Th1 and Th17)
- CD8 T cells - protect against intracellular infections
- many persist as memory cells


how do the intestinal microflora interact with the gut immune system (general 4 things)

- mucous layer
- intestinal epithelial cells
- development of lymphoid structures
- development of lymphocyte subsets


which PRRs are expressed on enterocytes and where are the located

- TLR 2 and 4 - apical
- TLR 3, 7 and 9 - in endosome
- TLR 5 - expressed on baso-lateral surface


Direct effects of microbiota on mucous layer and gut epithelium

block binding sites
produce bacteriocins
(Inhibit pathogen binding)


indirect effects of microbiota on mucous layer and gut epithelium

interact with PRRs on enterocytes
SCFA effects
IL22 effects


PAMP signalling via microbiota on enterocytes stimulates...

- mucin production
- proliferation of crypt enterocytes and Paneth cells
- release of antimicrobial peptides
- induction of regulatory cytokines (TGF-beta, IL-10)


how does the SCFAs produced by the microbiota affect the mucous layer and gut epithelium

inhibit NF-KB and the production of other inflammatory cytokines


development of Peyers patches, mesenteric lymph nodes and ILFs

peyers patches and mesenteric LN develop prenatally
ILFs develop post natally


what initiates the development of ILFs

signalling by microbiota


why do Peyers patches enlarge after birth

microbes of the microbiota enter via M cells and initiate further development


difference between response of the body to microbiota and pathogens

normal microbiota - induce physiological inflammation (without damage to the host)
pathogens - induce pathological inflammation (damages the host)


how does the gut discriminate between microbiota and pathogen in general

1. position and number of the bacteria
2. detect invasion
3. differential interaction with PRRs


what is the difference between microbiota and pathogen in regards to position and number

commensals found at the luminal edge of the mucous layer
pathogens bind tightly to invade the epithelial surface due to adhesins, invasins etc


how does the gut epithelium detect invasion

- TLR5 (at basolateral surface) activated
- damage via ROS and RNS detected by intracellular PRR


how does the gut epithelium discriminate the different interactions of PRRs of microbiota and pathogen

inflammasome signalling
Type 3 secretion systems


what is kwashiorkor

severe form of acute undernutrition


how does the microbiota influence kwashiorkor

dysbiosis of microbiota affects the risk for kwashiorkor


what is the hypothesis role of gut microbiota and nutrition

gut microbiota provides genes necessary for healthy growth and development


what does Kwashiorkor microbiota do?

generates chemical products that result in selective inhibition of TCA cycle enzymes --> effect on energy metabolism


high fat diets/obesity is associated with what kind of microbiota

a decrease in diversity of microbiota - number of bacteria are the same but just less diverse


what is the connection between microbiome and T2DM

those with T2DM have an altered and PREDICTABLE microbiome


individuals with low microbial diversity of their microbiome have what?

higher levels of insulin resistance, serum triglycerides, cholesterol and insulin


how is obesity associated with low grade chronic infection

causes increased intestinal permeability --> activates more PRRs: causing:
- induction of inflammatory cytokines (TNF-alpha, IL-1, IL-6 and IL-17)
- increase in mast cells, T cells and macrophages


what can the chronic low grade inflammation of obesity lead to

densensitisation of the insulin receptor and leptin receptor signalling


what causes inflammatory bowel disease

elevated immune responses against intestinal microflora


what is the bacterial diversity of people with IBD

bacterial diversity is reduced


intestinal permeability in people with IBD is increased or decreased?



what is the current theory about why people with IBD start to make immune responses against their microflora

defective signalling through PAMP-PRR interactions leads to persistence of microorganisms and their products resulting in persistent invasion --> leading to recurrent or chronic inflammation
(instead of physiological inflammation --> chronic pathological inflammation)


how is the microbiome associated with the development of allergies

Postulate the pre and postnatal microbial interactions very early in childhood by certain commensals signal for differentiation to a regulatory phenotype


what are the bacteria associated with allergic atopy?

higher incidence of Clostridia
low levels of Bifidobacteria


alteration of microbiota can cause which types of GIT disease

- susceptibility to GI pathogens
- overgrowth of Candida --> diarrhoea
- overgrowth of Clstridium difficile --> pseudomembranous colitis


what kind of bacteria is Clostridium difficile

gram positive, anaerobic, spore forming, rod


how does an overgrowth of Clostridium difficile cause pseudomembranous colitis

adheres to mucosal epithelium and produces cytotoxic toxins that cause cell death, inflammation and bowel necrosis


treatment of Psuedomembranous colitis

metronidazole +/- vancomycin


patients with recurrent Clostridium difficile infections posses microbiota characterised by

reduced diversity


treatment of recurrent C. difficile pseudomembranous colitis

faecal transplant!!