Lecture 8 - Microbiota Flashcards
decrease in diseases such as mumps, measels over the years has been paralleled by what?
increase in autoimmune diseases - e.g type 1 diabetes
What does the hygene hypothesis say?
inverse correlation of the types of allegies and the size of the families.
Therefore, reduced exposure to infectious agents caused a dysregulated immune response
What are the problems with the hygene hypothesis?
Some bugs stimulate autoimmune response by molecular mimicry
not the same in all countries i.e Japan
What does the old friends hypthesis say?
humankind has been exposed to bugs throughout history and this microbiota is training our immune system to respond to things that it needs to not just everything that it sees.
Diet hypthesis has been added to this, what does it stipulate?
diet drives changes in the microbiota and directs the development and function of the immune system
germ-free mice will have dysfunctional immune responses
What are the factors of nutritional transition?
economic factors
demographic - death/birth rates in society
epidemiological - societies with less infectious disease, good healthcare causing reduction in disease outcomes
Is diet the basis of increased “western world” disease?
high fat high sugar diets, less fibre which influences our microbiota
A change in microbial composition can lead to …
Dysbiosis
The gut microbiota contains approx how many micro-organisms?
10 trillion
lots of genetic potention at least 5 million genes (500 different species)
There is species specific segreation along the different…
segments of the GIT
What is the significance of germ free mice?
They have different genetic backgrounds, can selectively restore microbiotas
Taxonomic and metabolic classification of microbiota can be achieved with…
High through-put DNA sequencing
what was the first and second phase goals for the human microbiome project/
First phase: chracteristed composition and diversity (nose, moth, skin etc)
evaluate genetic metabolic potential
second phase:
creation of the first integrated dataset of biological properties from both the microbiome and host from cohort studies of microbiome associated diseases
What is a healthy microbiome?
Each persons microbiome is unique
Two people may have different microbioal communitites but still be healthy
Certain communities can be used to predict characteristics, what are some examples
whether they were breastfed, education
True or false
There are related species in different communities in the same body e.g skin GIT
true
What are the major groups of phylum in the gut?
firmicutes, bacteroidetes
but - no core microbiome, at least at the species level
True or false
Diet is more important in shaping gt microbiota than ethnicity, sanitation, hygene, geography and climate
true
What are the functional classes of non-pathogenic members of microbiota/
probiotics - transient - can confer health benefit and affect beneficial bacteria
autobionts: permanent - symbiotic, direct influence on host immune function
pathobionts: permanent, parasitic, do not cause disease in presence of autobionts - but can when there are alterations
What adaptations have the autobionts made to adapt to life in the gut?
They express plysaccharide utilisation loci (PUL
- digest plant polysaccarides that make up dietary fibre
Bacteria produce what important end products?
Short chain fatty acids (SCFA)
acetate
propionate
these can be used by other bacteria and our own endothelium
What is the role of SCFAs, generated by autobionts, have what role in gut health?
Sensed by epithelial cells - increased mucous production - gut protection
Stimulates B-cells to produce IgA
stimulates tissue repair
regulate other immune cells
To summarise what is the importance of gut microbiota?
Digestion
production of vitamins
gut epithelial development (and nutrition)
immune system development
tolerance
combat infections (barrier function, competitive exclusion)
The increase in obesity underlies the worldwide increase in ..
type 2 diabetes - insulin resistance occurs in parallel
What is the role of gut bacteria in obesity and type 2 diabetes?
There are changes in gut microbiota of obese and t2d patients
There is a decrease in gut diversity assoc with weight gain - a less complex popuation
Theres also a reduction in certain SCFAs including butyrate, which decreases the protection against opportunistic pathogens
cohousing oexperiements shwoed that obese phenotype in mice could be overcome by precense of mice with..
lean microbiota
Why is gut microbiota changed during pregnancy?
weight gain, insulin insensitivity
changes in immunity and dysbiosis reinforce each other
transfer of microbiota from pregnant women to germ-free mice leads to weiht gain/ insulin insensitivity
what is involved in the modulation of host metabolism by SCFA?
GPC-R respond to specific metabolites -
Activates:
PYY which regulated gut motility
GLP-1 - increase insulin sensitivity
IGN - SCFAs are converted to glocse
Fiaf - inhibits lipproteinlipase and fat accumulation in adipocytes
GPR43 deficient mice tend to be…
obese on a lean diet
with a high fat diet they are susceptible to
Diet induced gut dysbiosis also causes changes in what else?
balance of T-cells and CD4+ helps - SCFAs influence this
abundance of pathobionts and release of endotoxin
breakdown in gut barrier function and increase in gut bacteria and antigensin blood
The balance between Th17 and Tregs is important for…
the balance between immunosuppression and inflammatory responses
How does dysbiosis affect the balance of th17 and tregs?
Butyrate promotes formation of t regs and suppresse activation of th17s
cd4+ are activated by pathobionts (which are more active when the balance is lost)
Dysbiosis can also influence other organs including
bowel disease
behavioural problems
what are the ways to treat microbiota problems?
diet - less fat, more fibre
pro/prebiotics introduction
fecal transplantation
The risk of immunoallergic disorders is greater..
the earlier a migrant moves from region of low risk to region of high risk
The two way interaction between microbiota and immune sysmte is established early in life
Do prebiotics work? (yakult)
yes, but they require long term use - are cleared very quickly
