lecture 2) The human microbiome Flashcards
define microbiota
microorganisms in a specific environment
define microbiome
microbes + genome + environmental interactions
define dysbiosis
microbial imbalance on/in body (balance = healthy individual)
describe the co-evolution hypothesis
allow each other to live and evolve together
imbalance causes disease ??
what is the microbial pooprint?
DNA/genetic fingerprint of faeces
why is diversity in bacterial gut populations important?
coping mechanism for change eg. stress/infection
name a drawback of using antibiotics
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?)
what do gut microbiomes do?
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
what makes a person healthy?
structure microbiome adding to cell health?
just human cells?
pros and cons of removing microbes
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
when is microbial extinction reasonable?
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
describe the health hypothesis and give a reference
Strachan, 2000
cleaner lifestyle = weaker immune system
eg. clean water, c-section,pre-term antibiotics
describe the old friends hypothesis and give a reference
Rook, 2003
an increase in hygiene = loss of microbes = imbalance in microbiota therefore causing new infections to arise
are healthy people free of microbes?
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
determine which is cause and which is effect using psoriasis as an example
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?
which organ is the most heavily colonised organ in the human body?
gut
70% of all microbes in the body are in the gut
eg lactobacillus in small intestine, streptococcus in oesophagus, enterococci in small intestine
what are the 2 phyla in the gut microbiome?
bacteriodetes eg bacteroides
firmicutes eg clostridium
describe how bacterial abundance changes as you go down the GI tract. why is this?
increases down GI tract from stomach to colon
stomach pH = 2, acidic
pH decreases down the gut therefore more bacteria can live
what is the evidence that obesity can alter your gut microbial ecology?
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?
what is the evidence for obesity-related shift in human microbiota? give a reference
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?
describe the evidence for microbiota-mediated ‘transmission of obesity’ and give a reference
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
does an obese microbiome make you more obese?
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
what does inflammatory bowel disease cover?
crohns disease and ulcerative colitis
what is the gene in IBD that encodes for the mutated protein and what is it’s function?
Nod2: intracellular sensor for bacterial peptidoglycan
what causes the mutation in crohns disease?
it has 3 Nod2 polymorphisms
each polymorphism gives reduced activation of NF-kB
what protein is encoded by Nod2?
NF-kB
what is the function of NF-kB?
its a protein complex that controls transcription of DNA, cytokine production and cell survival
why is Nod2 function important?
needed for optimal defensin expression
v important in antimicrobial peptides
critical component of innate immune system
what type of bacteria do people with dysfunction Nod2 have more of?
E. coli
is there a function of microbes to increase/decrease predisposition of CD? give a reference
Kang et. al., 2010
faecalibacterium promoted production of anti-inflammatory cytokines and inhibits the production of pro-inflammatory cytokines
what is the impact of faecalibacterium action for CD patients?
less inflammation (not found in healthy individuals) adaptation of microbiome to aid against disease
could we cultivate microbiota from gut microbiome of CD patients to help other patients?
could be an effective probiotic for treatment of CD
eradication therapy against harmful components of microbiota eg heliobacter pylori and gastric carcinoma
