Gut microbiota & disease

Question 1

what does transit time affect?

Answer 1

• bacterial populations (due to different bacteria growth rates)
• intestinal cell exposure to toxins

Question 2

how do Bacterial populations change down GI tracts

Answer 2

become more anaerobic

Question 3

where are facultative found & where are obligate?

Answer 3

facultative- upper GIT

obligate- colon & LI

Question 4

dominant bacteria change along GIT depending on?

Answer 4

o2 concentration, pH and transit time

Question 5

what does GIT microbiota do? (6)

Answer 5

• defence against pathogens
• modification of host secretions
• metabolism of dietary components
• development of immune system
• production of essential 2ndary metabolites
• host signalling: gut-brain axis

Question 6

what are the 3 actions of defence against pathogens ?

Answer 6

barrier function, pH inhibition & competition

Question 7

what do LI microbes feed on

Answer 7

fruit, veg, wholegrains & pulses

Question 8

benefits of including dietary fibre in diet

Answer 8

• improves faecal bulking
• eases passage
• quicker transit time (reduced exposure to toxins)

Question 9

what does fibre contain that is important

Answer 9

phytochemicals, antioxidants and vitamins

Question 10

outline why bacterial fermentation is important

Answer 10

• releases additional phytochemicals
• maintains slightly acidic pH
• essential supply of SCFA
• increased commensal bacterial population

Question 11

where does protein metabolism take place?

Answer 11

mostly in distal colon

Question 12

products of protein metabolism?

Answer 12

branched SCFA (iso-butyrate, iso-valerate), phenols, indoles, amines 
essentially mainly pro-inflammatory molecules
HENCE why most intestinal disease starts in distal colon

Question 13

what affects production of microbial metabolites?

Answer 13

what we eat

Question 14

When microbes ferment food, produce a range of products that may be…

Answer 14

• excreted
• absorbed
• used by other microbes in LI for own growth

Question 15

3 main SCFA products are? and ratios

Answer 15

acetate, butyrate & propionate

3A:1B:1P

Question 16

what is butyrate important for

Answer 16

important for epithelial cell growth & regeneration

Question 17

what is acetate important for

Answer 17

transported in blood to peripheral tissues & lipogenesis

Question 18

what is propionate important for

Answer 18

gluconeogenesis in liver & satiety signalling

Question 19

what is barrier effects?

Answer 19

large numbers of indigenous microbiota prevent colonisation of pathogens

Question 20

how does competitive exclusion work?

Answer 20

microbes exclude incoming bacteria by producing specific compounds that destroy them

Question 21

where are SCFA found in high concentration

Answer 21

proximal colon–> lower pH

Question 22

at what pH do pathogens generally grow optimally

Answer 22

> 6

Question 23

what is low pH also good for?

Answer 23

Ca absorption

Question 24

in LI how many layers of mucus line epithelial cell surface?

Answer 24

2

Question 25

what else are SCFA important for?

Answer 25

important signalling molecules | -re-absorbed back into bloodstream & important for gut, brain & metabolic health

Question 26

what do receptors in gut epithelial cells do in response to detecting SCFA?

Answer 26

secrete gut hormones

Question 27

outline some of these receptors and what they secrete

Answer 27

GPR43/FFAR2- activated by acetate, propionate more than butyrate - results in GLP-1 secretion GPR/FFAR3- activated by propionate and butyrate - results in PYY secretion GPR109A- activated by butyrate - results in release of anti-inflammatory cytokines ie IL-10

Question 28

summary of IBD microbiota studies?

Answer 28

- reduced bacterial diversity (more of certain types of bacteria ie proteobacteria like E.Coli & less of firmicutes ie gram+ves) - protective bacterial species ie faecalibacterium prausnitzii found to be less abundant in IBD patients

Question 29

Consequences of exposure to Abx

Answer 29

- reduced bacterial diversity due to selective pressure - kill commensal bacteria - change bacterial composition (both long +short term)

Question 30

what else is selective pressure responsible for?

Answer 30

enabling different bacteria to survive--> spread of Abx resistance

Question 31

what generally happens to bacterial populations w Abx use

Answer 31

Generally firmicutes and Bacteroidetes decline and proteobacteria (pathogenic) increase

Question 32

what happens to diversity when Abx withdrawn?

Answer 32

usually recovers; temporary effect on microbiota however diversity might not regain original diversity

Question 33

what is the period of reduced diversity an ideal opportunity for?

Answer 33

C.Diff colonisation

Question 34

what can reduce incidence of CDAD

Answer 34

Rx w probiotics

Question 35

most effective treatment of CDAD

Answer 35

FMT (Effective in >90% patients vs 35% w vancomycin)

Question 36

what is the impact of low carb diet on gut microbiota

Answer 36

sig reduction in butyrate producing bacteria--> reduced SCFA

Question 37

what are probiotics?

Answer 37

- Live microorganisms that, when administered in adequate amounts, confer a health benefit on the host - are added live bacteria ie yoghurts etc

Question 38

what are prebiotics?

Answer 38

- Substrate that is selectively utilised by host microorganisms to confer the health benefit (food for resident bacteria) - found in leguminous veg

Question 39

what is a function of prebiotic?

Answer 39

stimulate SCFA production by gut microbiota; interact directly w host cell receptors

Question 40

what are prebiotics also good for?

Answer 40

improved Ca uptake