Gut Models Flashcards

(67 cards)

1
Q

What are the functions of the GI tract?

A
  • nutrient absorption

- protection from harmful components

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2
Q

What are the parts of the GI tract?

A
  • Upper tract: oral cavity, esophagus, stomach, duodenum, jejunum, ileum
  • Lower tract: colon, cecum, rectum, anal canal
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3
Q

What is the function of the mouth?

A

mastication + saliva –> bolus

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4
Q

What is the function of the stomach?

A

enzymes + acid –> chyme

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5
Q

What is the function of the small intestine?

A

bicarbonate + pancreatic juice + bile acids
brush border enzymes
- absorption
- further degradation

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6
Q

What are the functions of the large intestine?

A
  • water absorption

- microbiota

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7
Q

What are the functions of the microbiota in the small intestine?

A
  • digestion of food components and prebiotics (indigestible complex polysaccarides)
  • diet affects microbiota composition and function
  • microbiota ferments complex CHO, proteins –> SCFA & other metabolites
  • impact on mucosal and systemic immune responses
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8
Q

What is the enzyme contained in the saliva?

A

amylase

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9
Q

What is the food called in the mouth once it is mixed with saliva?

A

bolus

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10
Q

What type of enzymes are in the stomach?

A

proteases
lipases
acids

ex: pepsin is an enzyme that is activated by acids in the stomach

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11
Q

What is the food mixture called in the stomach?

A

chyme

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12
Q

What is the first thing that happens to chyme once it passes into the small intestine?

A

bicarbonate is released to increase the pH of chyme since coming from stomach the ph of it is 1-2 where the enzymes of the small intestine do not function.

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13
Q

What are the digestive juices that are released to the small intestine from the pancreas?

A

trypsin

chymotrypsin

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14
Q

What are the functions of the gallbladder?

A

It releases bile acids that help emulsify the products of lipid hydrolysis so that they can form micelles in order for them to be absorbed.

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15
Q

What else contributes to digestion in the small intestine other than pancreas and gallbladder?

A

there is also cells (enterocytes) on the walls of the small intestine that have brush border enzymes. These enzymes are a part of the plasma membrane of the enterocytes and they continue to break down further the FAT, PRO, CHO

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16
Q

Give examples of the brush border enzymes?

A

maltase, sucrase, isomaltase, peptidase, etc.

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17
Q

Where does the most amount of absorption occur?

A

jejunum by the enterocytes, once they are absorbed into the cells, they undergo further degradation with cellular proteases before they get into the lymphatic system.

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18
Q

Where do the absorbed nutrients go?

A

Water soluble nutrients are absorbed into the blood stream and travel to the liver via the hepatic portal vein.

Fat soluble nutrients are transported into the lymph vessels after they are assembled into chylomicrons, then they reach the blood after further processing.

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19
Q

What are prebiotics?

A

Prebiotics are molecules that reach the lower GI undegraded and unabsorbed such as complex polysaccharides

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20
Q

What are the short chain fatty acids that the gut microbiota can produce?

A

acetic acid
propionic acid
butyric acid

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21
Q

What are the functions of the SCFA in the gut?

A

They provide energy to the enterocytes which has an effect on gut health but also systemic health.

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22
Q

Why don we prefer in vitro studies for gut models?

A
  • ethical concerns
  • can test multiple molecules of the same family
  • takes shorter time
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23
Q

What are the key considerations of digestion models?

A
  • should be simple but not too simple
  • what has been done previously may not always be the best
  • sample collection depends on planned measurement
  • many aspects of digestion are not accurately reproduced by any available digestion model
  • must use judgement in decision making
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24
Q

What are the samples that are collected from the digestion model called?

A

Digesta

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25
What is the rate at the food leaves the stomach?
1-2 kcal/min
26
Define bioavailability
fraction of ingested component available at the site of action for utilization in normal physiological functions
27
What are the 3 main steps that are involved in bioavailability?
- digestibility/solubility - absorption (intestinal cells) & transport into circulation - incorporation to the functional entity/target
28
What are the two concepts that bioavailability include?
- bioaccessibility | - bioactivity
29
How is bioavailability established?
doing in vitro studies
30
What is bioaccessibility?
the fraction of compound that is released from its food matrix within the GIT and becomes available for intestinal absorption
31
How is bioaccessibility established?
doing in vivo studies
32
What can we see in vitro in terms of bioaccessibility and what can we not see?
We can see the sequences of events that take place during digestion in order to transform the potential bioaccessible material but that does not include assimilation of absorption through the epithelial tissue or even first pass metabolism or hepatic metabolism.
33
What is bioactivity?
- how the nutrient or bioactive compound is transported and reaches target tissue - how it interacts with biomolecules - its metabolism/biotransformation - physiological responses induced
34
True/False Bioavailability includes bioactivity
TRUE
35
What is the static digestion model and what are its phases?
everything is happening in one vessel - Phase 1: pepsin - Phase 2: pancreatic enzymes - Ultrafiltration - Freeze-drying - Storage
36
What are the conditions in which static digestion model happens?
incubation time: 15 min pepsin temperature: 37 ph: maintained at 7.4 enzymes (how much of it you put in is important)
37
How does the static model mimic the agitation of the stomach?
magnetic rod
38
What are the advantages of the static digestion model?
- the simplest - simulate physiological conditions (temp, ph, enzyme/chemical composition) - simulate sequence of events (2 or 3 steps: oral, gastric, intestinal)
39
What are the disadvantages of the static digestion model?
- do not mimic physical processes | - Products immobile in a single static bioreactor
40
What are the steps involved in using the static digestion model?
- take your food and homogenize it - put it in vessel and adjust the ph, temperature... - take samples from the mushy food - filter and centrifuge - take the liquid part and assess the nutrient of interest and determine the solubility of it
41
What are the considerations of static digestion model?
- chemical/enzymatic composition of saliva, gastric juice - incubation time - temperature - ph adjustment - peristaltic frequency - osmolality
42
Why don't most methods include the oral phase?
- process lasts seconds to ten minutes - no significant dissolution of compound from food samples - most difficult to stimulate for solid foods
43
Explain the gastric phase of the static digestion model
HCl-pepsin ph 1-2 1-3h infant digestion 4ph
44
Explain the intestinal phase of the static digestion model
- neutralization of acid - pancreatic enzymes - bile salts - ph 6.5-7.5 - 1-5h
45
What are the considerations for enzymes in static digestion model?
- choice of enzymes & incubation conditions depend on study objective
46
What are the pros and cons of using single enzyme in static digestion model?
pro: standardization, reproducibility con: less representative of in vivo conditions
47
What are the pros of static digestion models?
- low cost - evaluate the influence of digestion conditions - effect of food structure - food composition - dietetic factor (interactions between food components) - food processing (thermal and other treatments, fermentation - bioaccessibility
48
Give an example of a study that can be done on static gut model
vitamin D fortification on vegan cheese and how accessible it is
49
What are the cons of static digestion models?
- do not reproduce the dynamic environment of intestine - cannot access uptake/absorption - cannot assess transport kinetics - cannot measure nutrient competition at the site of absorption - no mucosal barrier, hormonal, nervous control, complexity of peristaltic movements, gastric emptying, continuous ph - Cannot evaluate factors influencing bioavailability such as nutritional status, age, genotype, pregnancy, lactation, obesity, infections etc. ex: poor iron status will increase absorption, elderly have slower transit time.
50
Explain the dynamic digestion model
flow of food from one compartment to another | dynamic ph, digestive enzymes, and bile concentrations
51
What are the two types of dynamic digestion models
monocompartmental | multicompartmental
52
What are the objectives of the dynamic gastric model?
- stimulate biochemical and mechanical processes of gastric digestion - bioaccessibility - effect of food structure on dissolution - survival and delivery of functional foods/drugs
53
What are the pros and cons of DGM?
Pros: - accurately processes real food items/meals as eaten - stimulates gastric mixing, transit, and breakdown forces - adjusts acid and enzyme addition based on food matrix - provides samples at any time Cons: - no oral phase, no intestinal phase
54
How does the DGM mimic peristasis?
pressurization of the water jacket around it
55
How does the DGM mimic gastric emptying?
piston that moves up and down which draws food into the antrum
56
Explain the human gastric simulator (hgs)
- gastric digestion - can incorporate oral and or small intestinal stages - flexible gastric vessel - continuous peristaltic contractions - controllable secretions
57
What are the pros and cons of HGS?
Pros: - can study physical and chemical breakdown of food - gastric secretion rate, ph, gastric emptying can be controlled - can be used with larger meal volumes Cons: - needs more complete validation in vivo data - sample size is large and may be costly
58
Explain the artificial colon ARCOL
- reproduces colonic environment - anaerobic environment maintained via microbiota metabolic activity - maintains ph, temperature, anaerobiosis, colonic residence time - complex, high-density, metabolically active microbiota - dialysis system
59
Name the materials that can be found in ARCOL culture medium
- CHO - Protein - Lipids - Minerals & Vitamins
60
What are the pros and cons of ARCOL?
Pros: - wireless system, maintains anaerobic conditions via activity of microbiota - dialysis (passive absorption of microbial products - effect of compounds of interest on microbiota composition and activity Cons: - Does not simulate the different conditions associated with the 3 parts of the colon. (ph, retention time, availability of substrates, microbiota
61
Name 3 monocompartmental digestion models
Dynamic Gastric Model (DGM) Human Gastric Stimulator (HGS) The Artificial Colon (ARCOL)
62
Explain DIDGI
- Stomach and small intestine - computer-controlled - reproduces gastric and intestinal transit times, pH, sequential addition of digestive secretions, stirring contents - 2 consecutive compartments - glass jacket with H2O at 37C - temp and ph and redox sensors - computer-controlled pumps regulate flow rate - N2 purging - no dialysis membrane
63
What are the pros and cons of DIDGI
Pros: - robust, foods & meals up to 200g - Transparent compartments - mimics well biochemical and physical processes Cons: - mixing and stirring is not realistic - no nutrient absorption
64
Explain TIM
- GI conditions and colon microbiota can be simulates - extensively validated - compartments: stomach, duodenum, jejunum, ileum - mimics dynamic conditions in the upper GI - TIM-2: colon - computer controlled - highly published
65
What are the pros and cons of TIM?
Pros: - accurate simulation - specific food ingredients and meals - can simulate average GI conditions or disease conditions - easy sample collection - highly reproducible Cons: - No feedback on energy density - No intestinal mucosa
66
Explain SHIME
- 5 reactors: stomach, small intestine, ascending, transverse, descending colons - retention times and ph of different vessels resemble in vivo - fecal microbiota inoculation --> stabilization --> representative microbial community in each colon compartment, different in composition and functionality - additional absorption unit (SI absorption) - an added molecule: host-microbiota interactions
67
What are the pros and cons of SHIME?
Pros: - 2-4 full GIT in same system - Volumes close to in vivo - Intestinal microbiota in 3 different colonic compartments - up to several months - can evaluate host- Cons: - No water/metabolites absorption in the colon - mixing by pumping/stirring