Microbiota Flashcards
Which bacteria commonly cause overgrowth in the microbiota?
Candida
Clostridium difficile
How many genes are provided to us by our microbiota?
10^6
What leads to pseudomembraneous colitis?
Antibiotics use (particularly broad spectrum)
Cytotoxic drugs
Which immune cell do lean people have more of?
Tregs
What does the appendix do for the microbiota?
It is a reservoir for bacteria - as reflected by higer incidence of
C. difficile overgrowth in patients with appendectomies
How does having a caesarian section effect the microbiota?
It takes longer to develop
What is the function of hte mucous layer/ glycocalyx
Holds the bacteria at arms length
How similar are the microbiota of identical twinss?
50%
Innate lymphoid cells of the GIT resemble which other class of immune cell most?
Multi-subsets, cytokine secreting that resembles a Th subset
What does alpha4beta7 bind to on vascular enthelium of all mucosal surface?
MAdCAM-1
Which vitamins are made entirely by the microbiota (from dietary sources)?
B12, folate, K, biotin
How is the micrbiome’s response to a nutritious diet different in children with Kwashiorkor cf those without?
The diversity of the microbiome in children with Kwashiorkor doesn’t increase in response to a change from Malawian diet to nutritious diet cf to health children
How much does the microbiota weigh?
1-2kg
What is one important implication of alpha4beta7 homing activated T and B cells to all mucosal surfaces (more than just the GIT’s)?
B cells will go to the breast tissue > IgA is secreted in milk for the infant’s protection
How does the GIT epithelium and lymphoid tissue differentiate the microbiota from pathogens?
Pathogens are close to the epithelium, the microbiota are held at arms lengths
Pathogens can be invasive, detected by intracellular and apical PRRs
What do lymphoid tissue inducer cells do?
Stimulate recruitment of DCs, T cells and B cells to Peyer’s patches and isolated lymphoid follicles
What is a immunomodulatory molecule secreted by enterocytes?
TGF-beta
What is the aetological agent of pseudomembranous colitis?
Clostridium difficile
What is TLR 5 for?
Flagellum
How can you characterise the microbiota of people with type 2 diabetes?
It is altered in a predictable way
Overall the microbiota in obese people is…
Differs in composition
Altered fermentation
Greater energy absorption
What is the difference between pre- and probiotics?
Prebiotics are dietary supplements that promote healthy microbiota
Probiotics are live organisms ingested to improve the health of the microbiota
Do goblet cells secrete more than just mucous? So if, what?
Yes
Lysozyme
Lactoferrin
What is Kwashiorkor?
A wasting disease associated with malnutrition that is predmoninantly found in Africa
What is the microbiome?
The total of all the genes provided to us by the microbiota
Which site has more micro-organisms, the throat or skin?
Throat
Apart from M cells, what other cells delivery Ag across the gut epithelium?
Goblet cells
What does ILF stand for?
Isolated lymphoid follicle
T/F DCs can only get their Ag from M cells or goblet cells
False, they can also project their process through tight junctions directly into the lumen of the gut
In the steady state how do DCs direct T cell maturation?
Towards Treg and Th2
What is the third signal for IgA isotype switching?
TGF-beta
What genes does the microbiota of obese mice have more off?
Carbohydrate metabolism = greater energy extraction
Why is vaginal delivery better?
Allows rapid acquision of Firmicutes and Bifidobacteria
What is the function of interepithelial lymphocytes in GIT defence?
Host protection
Epithelial repair
Promoting tolerant DCs
Secrete IL-22
What happens to patients intestinal permeability in inflammatory bowel disease?
It increases
What is an alternative treatment for recurrent pseudomembraneous colitis recently introduced?
Faecal transplant
How does the microbiota effect angiogenesis?
It induce host gene changes
What is the meaning of physiological inflammation?
The microbiota induced changes to the mucosal immune response that promotes the development of a protective innate and adaptive immune system
Which amino acids do the microbiota particularly help provide?
Lycine
Threonine
What effect do PAMPs from microbiota have? How do they do that?
Increase defence against pathogens
Stimulate more mucous production, Paneth cell replication, anti-microbial peptide secretion
Tone inflammatory response and promote immune regulation
How does the microbiota develop with age?
It diversifies
Which metabolic process was the Kwashiorkor microbiome found to adversely affect?
TCA cycle
Are eukaryotes part of the normal microbiota?
Yes
What is an alteration in our normal microbiota called?
Dysbiosis
How were non-culturable bacteria identified?
Meta-genomics
When do isolated lymphoid follicle develop in humans?
Postnatally
In mice, the numbers of which bacteria increases in response to a iron free diet?
Bifidobacteria/ Clostridia
Which cytokine is particularly important for the gut immune defence?
IL-22
How does a High fat / low fibre diet affect the microbiota?
Decreases its diversity
How do DCs direct T cells under inflammatory conditions?
Into the develop of Th17 and Th1
How much IgA can be produced by B cells?
40mg/kg of IgA/day
Sterile mice have smaller what?
Peyer’s patches and less lymphoid tissue
The microbes present in the first few months of life must do what?
Lactose fermentation
What mediates the low grade inflammation seen in obese people?
More inflammatory cytokines - TNF-alpha, IL-1, IL-6, IL-17
More mast cells, T cells and macrophages
What is IL-22 associated with in GIT defence?
Antimicrobial defence
Epithelial repair
Tight junction integrity
What must the gut’s immune system be able do?
Differentiate pathogens from normal microbiota and food antigen
How does the mode of a babies delivery effect the microbiota?
Vaginal is better than caesarian
What is a major function of NK in GIT defence?
Secrete IL-22
Are they aerobes in the lower GIT??
Yes
Some TLRs on enterocytes are downregulated after birth, which ones? Why?
TLR 2 and 4
To prevent over stimulation but GIT microbiota
What surgical precedure is associated with a greater risk of recurrent pseudomembraneous colitis?
Appendectomy
When do mesenteric lymph nodes develop in humans?
Prenatally
How are macrophages in the GIT different from elsewhere?
Express less TLRs therefore are hyporesponsive to TLR signalling
How many bacteria are in our gut?
10^12
What does MALT stand for?
Mucosal-associated lymphoid tissue
How does the microbiota of children change in response to exposure to different food?
It diversifies
What happens the bacterial diversity to patients with inflammation bowel disease?
It decrease
When do Peyer’s patches developed in humans?
Prenatally
What do individuals with low microbiota diversity have higher levels of?
Insulin resistance
Serum triglycerides
Insulin
Cholesterol
Where is TLR5 expressed on enterocytes? Why?
Basolateral surface
So only invasive pathogen activate it
What are the four most common phyla found?
Firmicutes
Bacteroidetes
Acinobacteria
Proteobacter
What does the microbiome’s genes help us with?
Helps with:
Metabolism
Development
Immune system
Protection against pathogens
T/F Everyone’s microbiota looks the same
False, each of us have a unique “fingerprint”
What phyla is most prevalent at a young age?
Firmicutes
What carbohydrates does the microbiota help digest?
Lactose
Cellulose
T/F Antibiotics only causes short term changes to the microbiota?
False, some can have long term affects (eg Vancomycin)
What type of viruses make up most of our microbiota?
Bacteriophages
How long does it take for one’s microbiota to be established?
2.5 years
What is rePOOPulate?
A mixture of 33 microbes to restoration of a healthy gut microbiota
What are the 2 postulated mechanisms to explain how the microbiota provides extra energy to the host?
- They directly provide nutrients from dietary substances eg vitamin B12
- They alter the host’s metabolism to help it metabolise carbohydrates and fats
What is the name of the homing molecule that direct activated B and T cells to the GIT epithelium?
alpha4beta7
Peyer’s patches are primarily located in which part of the GIT?
The small intestine
What antibiotics are used to treat pseudomembraneous colitis?
Metronidazole (+/- vancomycin if required)
Is the diversity at each site the same?
No, while the main 4 phyla are generally there, they’re in different proportions
T/F enterocytes secrete cytokines but not chemokines
False, they secrete both
What is the function of the pocket on the apical side of M cells?
Lymphoid cells sit there so they can catch Ag immediately
T/F the metabolic effect of the microbiota is the same across different sites despite the variation in phyla at those sites
True
What does MAIT stand for?
Mucosal associated invariant T cells
Where are our microbiota predominantly gram +ve?
Skin, throat and vagina
What cytokines is the third signal from Treg differentiation?
TGF-beta
Animal based diet is associated with what type of bacteria?
Increase in bile-tolerant bacteria
Decrease in bacteria that metabolise plant polysaccaride
