Flashcards in Microbiota Deck (73)
Loading flashcards...
0
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
1
predominant phyla of the gut
Bacteroidetes and Firmicutes
then Actinobacteria
Proteobacteria relatively rare
2
are the gut bacteria predominantly anaerobic or aerobic
anaerobic - 99.9%
3
what proportion of bacteria of the microbiota are shared between twins
<50%
4
the genes provided by the microbiota contribute to what
- metabolism (carbohydrates, vitamin metabolism/biosynthesis, energy, drugs)
- development
- the immune system
- protection against enteropathogens
5
what 6 factors can influence the gut bacteria
- mode of delivery
- age
- diet
- antibiotics
- genetics and environment
- chronic inflammation
6
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
7
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
8
what types of diets can influence the microbiota
- high fat/low fibre
- low fat/high fibre
- animal based
- plant based
9
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)
10
Which phyla of bacteria are bile resistant
Bacteroides
11
which antibiotic has long term effects on the gut microbiota?
vancomycin - gut microbiota dont go back to original
12
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
13
which dietary substances do the microbiota directly supply us
vitamin B2, vitamin K, biotin, folate
14
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
15
what do the microbiota do to carbohydrates
break down lactose, cellulose, mucins --> short chain fatty acids
16
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
17
which amino acids do microbiota especially metabolise for us
lysine and threonine
18
what is MALT
mucosa-associated lymphoid tissue
19
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
20
what is the role for ILFs and Peyers patches in the gut
sites for induction of T and B cell activation
21
innate defences of the gut in general
- peristalsis
- acid
- mucous layer/glycocalyx
- enterocytes
- innate lymphocytes
- mechanisms for "controlled" antigen access
22
explain the mucous layer of the gut
associated with the enterocytes - act as a molecular sieve, so the commensals held at "arms length"
23
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
24
how do goblet cells contribute to innate defenses
secrete mucins, lysozyme and lactoferrin - inhibiting the growth of micro-organisms
25
what are the innate lymphoid cells of the gut
lymphoid tissue inducer cells
intraepithelial lymphocytes (IELs)
NK cells
26
what do lymphoid tissue inducer cells do
stimulate recruitment of DCs, T and B cells to peyers patches and ILFs
27
Role of IL22 in innate gut immunity
enhances antimicrobial defence and epithelial repair and barrier integrity
28
what is special about the macrophages of the gut
they are HYPOresponsive to TLR signalling - hard to stimulate them
29
where are M cells located
directly over the sites of organised lymphoid aggregates
30
structure of M cells
possess a folded luminal surface (no villi)
lack a thick glycocalyx
dont secrete mucus
(microbial access easier)
31
function of M cells
deliver antigens directly to the cells in organised lymphoid aggregates
32
function of DCs in the gut
sample antigen from the intestinal mucosa and induce a variety of T cell differentiation pathways
33
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)
34
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
35
Main isotype switching of the gut and how
IgA via TGF-beta signal 3
36
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
37
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
38
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
39
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
40
Direct effects of microbiota on mucous layer and gut epithelium
block binding sites
produce bacteriocins
(Inhibit pathogen binding)
41
indirect effects of microbiota on mucous layer and gut epithelium
interact with PRRs on enterocytes
SCFA effects
IL22 effects
42
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)
43
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
44
development of Peyers patches, mesenteric lymph nodes and ILFs
peyers patches and mesenteric LN develop prenatally
ILFs develop post natally
45
what initiates the development of ILFs
signalling by microbiota
46
why do Peyers patches enlarge after birth
microbes of the microbiota enter via M cells and initiate further development
47
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)
48
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
49
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
50
how does the gut epithelium detect invasion
- TLR5 (at basolateral surface) activated
- damage via ROS and RNS detected by intracellular PRR
51
how does the gut epithelium discriminate the different interactions of PRRs of microbiota and pathogen
inflammasome signalling
Type 3 secretion systems
52
what is kwashiorkor
severe form of acute undernutrition
53
how does the microbiota influence kwashiorkor
dysbiosis of microbiota affects the risk for kwashiorkor
54
what is the hypothesis role of gut microbiota and nutrition
gut microbiota provides genes necessary for healthy growth and development
55
what does Kwashiorkor microbiota do?
generates chemical products that result in selective inhibition of TCA cycle enzymes --> effect on energy metabolism
56
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
57
what is the connection between microbiome and T2DM
those with T2DM have an altered and PREDICTABLE microbiome
58
individuals with low microbial diversity of their microbiome have what?
higher levels of insulin resistance, serum triglycerides, cholesterol and insulin
59
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
60
what can the chronic low grade inflammation of obesity lead to
densensitisation of the insulin receptor and leptin receptor signalling
61
what causes inflammatory bowel disease
elevated immune responses against intestinal microflora
62
what is the bacterial diversity of people with IBD
bacterial diversity is reduced
63
intestinal permeability in people with IBD is increased or decreased?
increased
64
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)
65
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
66
what are the bacteria associated with allergic atopy?
higher incidence of Clostridia
low levels of Bifidobacteria
67
alteration of microbiota can cause which types of GIT disease
- susceptibility to GI pathogens
- overgrowth of Candida --> diarrhoea
- overgrowth of Clstridium difficile --> pseudomembranous colitis
68
what kind of bacteria is Clostridium difficile
gram positive, anaerobic, spore forming, rod
69
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
70
treatment of Psuedomembranous colitis
metronidazole +/- vancomycin
71
patients with recurrent Clostridium difficile infections posses microbiota characterised by
reduced diversity
72
