Lecture 8 - Microbiota

Question 1

decrease in diseases such as mumps, measels over the years has been paralleled by what?

Answer 1

increase in autoimmune diseases - e.g type 1 diabetes

Question 2

What does the hygene hypothesis say?

Answer 2

inverse correlation of the types of allegies and the size of the families.

Therefore, reduced exposure to infectious agents caused a dysregulated immune response

Question 3

What are the problems with the hygene hypothesis?

Answer 3

Some bugs stimulate autoimmune response by molecular mimicry

not the same in all countries i.e Japan

Question 4

What does the old friends hypthesis say?

Answer 4

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.

Question 5

Diet hypthesis has been added to this, what does it stipulate?

Answer 5

diet drives changes in the microbiota and directs the development and function of the immune system

germ-free mice will have dysfunctional immune responses

Question 6

What are the factors of nutritional transition?

Answer 6

economic factors

demographic - death/birth rates in society

epidemiological - societies with less infectious disease, good healthcare causing reduction in disease outcomes

Question 7

Is diet the basis of increased “western world” disease?

Answer 7

high fat high sugar diets, less fibre which influences our microbiota

Question 8

A change in microbial composition can lead to …

Answer 8

Dysbiosis

Question 9

The gut microbiota contains approx how many micro-organisms?

Answer 9

10 trillion

lots of genetic potention at least 5 million genes (500 different species)

Question 10

There is species specific segreation along the different…

Answer 10

segments of the GIT

Question 11

What is the significance of germ free mice?

Answer 11

They have different genetic backgrounds, can selectively restore microbiotas

Question 12

Taxonomic and metabolic classification of microbiota can be achieved with…

Answer 12

High through-put DNA sequencing

Question 13

what was the first and second phase goals for the human microbiome project/

Answer 13

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

Question 14

What is a healthy microbiome?

Answer 14

Each persons microbiome is unique

Two people may have different microbioal communitites but still be healthy

Question 15

Certain communities can be used to predict characteristics, what are some examples

Answer 15

whether they were breastfed, education

Question 16

True or false

There are related species in different communities in the same body e.g skin GIT

Answer 16

true

Question 17

What are the major groups of phylum in the gut?

Answer 17

firmicutes, bacteroidetes

but - no core microbiome, at least at the species level

Question 18

True or false

Diet is more important in shaping gt microbiota than ethnicity, sanitation, hygene, geography and climate

Answer 18

true

Question 19

What are the functional classes of non-pathogenic members of microbiota/

Answer 19

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

Question 20

What adaptations have the autobionts made to adapt to life in the gut?

Answer 20

They express plysaccharide utilisation loci (PUL

- digest plant polysaccarides that make up dietary fibre

Question 21

Bacteria produce what important end products?

Answer 21

Short chain fatty acids (SCFA)

acetate
propionate

these can be used by other bacteria and our own endothelium

Question 22

What is the role of SCFAs, generated by autobionts, have what role in gut health?

Answer 22

Sensed by epithelial cells - increased mucous production - gut protection

Stimulates B-cells to produce IgA

stimulates tissue repair

regulate other immune cells

Question 23

To summarise what is the importance of gut microbiota?

Answer 23

Digestion

production of vitamins

gut epithelial development (and nutrition)

immune system development

tolerance

combat infections (barrier function, competitive exclusion)

Question 24

The increase in obesity underlies the worldwide increase in ..

Answer 24

type 2 diabetes - insulin resistance occurs in parallel

Question 25

What is the role of gut bacteria in obesity and type 2 diabetes?

Answer 25

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

Question 26

cohousing oexperiements shwoed that obese phenotype in mice could be overcome by precense of mice with..

Answer 26

lean microbiota

Question 27

Why is gut microbiota changed during pregnancy?

Answer 27

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

Question 28

what is involved in the modulation of host metabolism by SCFA?

Answer 28

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

Question 29

GPR43 deficient mice tend to be…

Answer 29

obese on a lean diet

with a high fat diet they are susceptible to

Question 30

Diet induced gut dysbiosis also causes changes in what else?

Answer 30

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

Question 31

The balance between Th17 and Tregs is important for…

Answer 31

the balance between immunosuppression and inflammatory responses

Question 32

How does dysbiosis affect the balance of th17 and tregs?

Answer 32

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)

Question 33

Dysbiosis can also influence other organs including

Answer 33

bowel disease

behavioural problems

Question 34

what are the ways to treat microbiota problems?

Answer 34

diet - less fat, more fibre

pro/prebiotics introduction

fecal transplantation

Question 35

The risk of immunoallergic disorders is greater..

Answer 35

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

Question 36

Do prebiotics work? (yakult)

Answer 36

yes, but they require long term use - are cleared very quickly