lecture 2) The human microbiome

Question 1

define microbiota

Answer 1

microorganisms in a specific environment

Question 2

define microbiome

Answer 2

microbes + genome + environmental interactions

Question 3

define dysbiosis

Answer 3

microbial imbalance on/in body (balance = healthy individual)

Question 4

describe the co-evolution hypothesis

Answer 4

allow each other to live and evolve together

imbalance causes disease ??

Question 5

what is the microbial pooprint?

Answer 5

DNA/genetic fingerprint of faeces

Question 6

why is diversity in bacterial gut populations important?

Answer 6

coping mechanism for change eg. stress/infection

Question 7

name a drawback of using antibiotics

Answer 7

strip the gut microbiome
can be changed for 2 years before returning to original state
could add to our wellness or make us more unwell (cost of getting rid of disease?)

Question 8

what do gut microbiomes do?

Answer 8

regulate the immune system
removes toxins
crowds out pathogens - colonisation resistance
improves intestinal functions
communication links between gut and brain
produces metabolites that are just as important as the ones produced by the liver
cell/cell and cell/microbe signalling

Question 9

what makes a person healthy?

Answer 9

structure microbiome adding to cell health?

just human cells?

Question 10

pros and cons of removing microbes

Answer 10

use of antibiotics to remove microbes that are causing infection eg penicillin for tonsillitis
BUT not all microbes are bad - eradication vs reduction
natural succession of microbiota from birth to later years
c-section babies have diff microbiota to birthed babies

Question 11

when is microbial extinction reasonable?

Answer 11

infections such as smallpox and polio are acceptable as they caused extreme mortality rates
microbial extinction in terms of microbiota in nose, mucosal layers etc isnt reasonable as these microbes protect us from serious infections

Question 12

describe the health hypothesis and give a reference

Answer 12

Strachan, 2000
cleaner lifestyle = weaker immune system
eg. clean water, c-section,pre-term antibiotics

Question 13

describe the old friends hypothesis and give a reference

Answer 13

Rook, 2003

an increase in hygiene = loss of microbes = imbalance in microbiota therefore causing new infections to arise

Question 14

are healthy people free of microbes?

Answer 14

No: undetected microbes eg some viruses persist (herpes), skin and mucous membranes constantly exposed to microbes and colonised (link to co-evolution hypothesis) microbial DNA evident in CSF, microbes that are present depends on the environment

Question 15

determine which is cause and which is effect using psoriasis as an example

Answer 15

skin microbiome condition
does the microbiome cause psoriasis
OR
do we have a pre-disposition to the disease that a certain environmental factor would influence?

Question 16

which organ is the most heavily colonised organ in the human body?

Answer 16

gut
70% of all microbes in the body are in the gut
eg lactobacillus in small intestine, streptococcus in oesophagus, enterococci in small intestine

Question 17

what are the 2 phyla in the gut microbiome?

Answer 17

bacteriodetes eg bacteroides

firmicutes eg clostridium

Question 18

describe how bacterial abundance changes as you go down the GI tract. why is this?

Answer 18

increases down GI tract from stomach to colon
stomach pH = 2, acidic
pH decreases down the gut therefore more bacteria can live

Question 19

what is the evidence that obesity can alter your gut microbial ecology?

Answer 19

mutation in gene of mice - more/less leptin
fimicutes and bacteroids have different properties in lean mice to obese mice
obese mice have more firmicutes and less bacteroids than lean mice
mutation in gene alters body weight regulation
change in genetics - change in body weight - change in microbiota
OR
are changes in microbiota making you obese, or both?

Question 20

what is the evidence for obesity-related shift in human microbiota? give a reference

Answer 20

Nature 2006
bacteria increase when dieting, change correlated with weight loss
52 weeks dieting and microbiota became a lot more similar to a lean person
*is the change in bacteroidetes abundance due to weight gain/loss or is it due to consuming certain dietary components?

Question 21

describe the evidence for microbiota-mediated ‘transmission of obesity’ and give a reference

Answer 21

Turnbaugh et. al., 2008
obese microbiome promoted weight gain in a germ-free mouse compared to lean microboime
faeces and saline fed to the mouse during this experiment

Question 22

does an obese microbiome make you more obese?

Answer 22

obese microbiomes better at harvesting food for energy (comparison of energy content in faeces of lean and obese mice)
increase in genes encoding enzymes for breakdown of dietary polysaccharides in obese mice
therefore, increased capacity of obese microbiome for energy extraction

Question 23

what does inflammatory bowel disease cover?

Answer 23

crohns disease and ulcerative colitis

Question 24

what is the gene in IBD that encodes for the mutated protein and what is it’s function?

Answer 24

Nod2: intracellular sensor for bacterial peptidoglycan

Question 25

what causes the mutation in crohns disease?

Answer 25

it has 3 Nod2 polymorphisms

each polymorphism gives reduced activation of NF-kB

Question 26

what protein is encoded by Nod2?

Answer 26

NF-kB

Question 27

what is the function of NF-kB?

Answer 27

its a protein complex that controls transcription of DNA, cytokine production and cell survival

Question 28

why is Nod2 function important?

Answer 28

needed for optimal defensin expression
v important in antimicrobial peptides
critical component of innate immune system

Question 29

what type of bacteria do people with dysfunction Nod2 have more of?

Answer 29

E. coli

Question 30

is there a function of microbes to increase/decrease predisposition of CD? give a reference

Answer 30

Kang et. al., 2010
faecalibacterium promoted production of anti-inflammatory cytokines and inhibits the production of pro-inflammatory cytokines

Question 31

what is the impact of faecalibacterium action for CD patients?

Answer 31

less inflammation (not found in healthy individuals)
adaptation of microbiome to aid against disease

Question 32

could we cultivate microbiota from gut microbiome of CD patients to help other patients?

Answer 32

could be an effective probiotic for treatment of CD

eradication therapy against harmful components of microbiota eg heliobacter pylori and gastric carcinoma